SURGERY,

THE ULTIMATE

PLACEBO

PROFESSOR IAN HARRIS AM, MBBS, FRACS, FAOrthA, MMed (Clin Epi), PhD is an orthopaedic surgeon in clinical practice in Sydney. He is also an academic (professor of orthopaedic surgery), with higher degrees (Masters and PhD) in evidence-based medicine and surgery. He directs a research unit that focuses on the outcomes of surgery and has published and presented widely in the field of surgical outcomes.

SURGERY,

THE ULTIMATE

PLACEBO

A SURGEON CUTS THROUGH THE EVIDENCE

IAN HARRIS

A NewSouth book

Published by

NewSouth Publishing

University of New South Wales Press Ltd

University of New South Wales

Sydney NSW 2052

AUSTRALIA

newsouthpublishing.com

© Ian Harris 2016

First published 2016

This book is copyright. Apart from any fair dealing for the purpose of private study, research, criticism or review, as permitted under the Copyright Act, no part of this book may be reproduced by any process without written permission. Inquiries should be addressed to the publisher.

National Library of Australia

Cataloguing-in-Publication entry

Creator: Harris, Ian Andrew, author.

Title: Surgery, the Ultimate Placebo: A surgeon cuts

through the evidence

ISBN:    9781742234571 (paperback)

9781742242309 (epub)

9781742247670 (epdf)

Subjects: Placebos (Medicine)

Surgery – Psychological aspects.

Surgery – Risk factors.

Medicine and psychology.

Dewey Number: 617

Cover design Xou Creative

All reasonable efforts were taken to obtain permission to use copyright material reproduced in this book, but in some cases copyright could not be traced. The author welcomes information in this regard.

CONTENTS

Introduction

1 The placebo effect

What is the placebo effect and how does it work?

2 The science of medicine – or lack of it

What makes ‘good’ evidence?

3 Building the perfect placebo

What makes a good placebo?

4 Putting surgery to the (placebo) test

Examples of studies using sham surgery

5 The surgical scrap heap

Operations that have faded away due to a lack of effectiveness

6 Today’s placebo surgeries

Current surgical procedures under question

7 Why do we still do it?

Reasons behind the persistence of surgery that is not effective

8 Surgery has a placebo effect – so what?

The case against using the placebo effect

9 What can we do about it?

As patients, doctors, researchers, funders and as a society

References

Acknowledgements

INTRODUCTION

THIS BOOK BUILDS a case for a placebo effect of surgery, something that is often underestimated when assessing the effectiveness of surgical procedures. This placebo effect is one of the factors contributing to the overestimation of the true effectiveness of surgery.

The aim of the book is to inform people, medical and non-medical, about the facts relating to the true effect of many of the surgical procedures performed today and in the past, and to provide a counter to the assumptions that any new operation must be better than the old one; that complexity in surgery is rewarded by increased effectiveness; and that a doctor would not recommend an operation unless it was effective and in the best interests of the patient. But to ensure that you do not take these comments the wrong way, some clarification is in order.

I am not suggesting that all surgery is ineffective or harmful. I am a surgeon and I spend a considerable part of my working life performing surgery. I am, however, a fairly conservative surgeon and tend not to operate when there is doubt about the balance of risks and benefits of a procedure. I rarely regret advising patients against surgery, and I am frequently surprised at how well the body repairs and adjusts itself without surgical intervention. Just as frequently, I see patients who have had questionable operations that have gone wrong, often resulting in the patient being worse off than they would have been without the surgery. It is fair to say that I am sceptical of many of the claims of surgery, because to be sceptical is to be scientific, and because scientific inquiry so often shows the effectiveness of many treatments to be less than initially claimed. In other words, I am sceptical because it is scientific, but also because my scepticism is so often rewarded.

Also, I am not suggesting that surgeons are recommending operations knowing that the potential risks outweigh the potential benefits. Largely, surgeons believe that they are doing the right thing, but often they are not aware of the strength (or weakness) of the supporting evidence or, what is more often the case, there is simply no substantial or convincing scientific evidence available, leaving them to rely on judgments based on their own perception. Without good scientific evidence, surgeons perceive the procedures they recommend to be effective, or they assume that they are effective – otherwise their colleagues wouldn’t be doing them, right? Put simply, a lack of evidence allows surgeons to do procedures that have always been done, those that their mentors taught them to do, to do what they think works, and to simply do what everyone else is doing. It is very hard to get into trouble if you are doing what is common practice and what has traditionally been done. My argument is that relying on tradition and unsupported perception frequently leads to an incorrect assessment of the effectiveness of the treatment, and is therefore not good enough.

I know this because I have learned it the hard way. When I started training and then practicing as a surgeon, decision making was relatively easy; paradoxically, the more you know, the harder it gets. This is because a conflict develops between what you understand to be true, based on scientific research, on the one hand, and what you observe, what you were taught, and what everyone else is doing on the other.

I have always been impressed by the scientific debunking of non-scientific beliefs. I remember many years ago, seeing a television program where two wellknown sceptics (James Randi and Dick Smith) showed water diviners to be no better than chance at detecting water in underground pipes, constructed as part of an experiment. The water diviners felt that they had been about 90 per cent correct, but were only just over 10 per cent correct, in picking water from one of ten pipes.

While I loved the scientific method used, I was fascinated by the reaction of the water diviners, who claimed interference from underground magnets and other things, despite being able to ‘detect’ water in the pipes in prior, ‘open label’ (unblinded) tests. Water diviners, using forked sticks or other devices, had been finding water pretty successfully for generations, and relied on tradition and observation to justify what they knew: that water divining was a good way of finding water. The fact that you could find water just about anywhere if you dug deep enough was not considered. They were just doing what they had always done and it worked – they were finding water. To them, if science showed water divining to be ineffective, it meant that there was something wrong with the experiment; the science was wrong.

I started my career like the water diviners: doing what everyone else was doing and what I was taught to do. And I was happy. And I thought my patients were happy, and most of them probably were. I was finding water, so I didn’t see much point in questioning the methods.

I started doing my own small-scale research (randomised trials comparing two treatments) to fill some gaps in the evidence, but soon became frustrated with my poor understanding of the scientific method. I was jealous of those who could critically appraise scientific studies. I didn’t even know there was ‘good’ and ‘bad’ science, let alone possess the ability to be able to distinguish between the two. I set out to obtain that knowledge, and in doing so I quickly realised that that the scientific method (so called ‘evidence-based medicine’) was the only way of reliably knowing things – that there were significant flaws in relying on observation and tradition.

In short, I realised that the kinds of tests that were applied to the water diviners – properly conducted scientific experiments – needed to be applied to surgery, and we needed to adjust our thinking so that we didn’t react like the water diviners when we were shown the evidence. If I was a water diviner, I would be hanging up my divining rod.

It is not my aim to sensationalise the lack of effect of surgery, nor do I aim to present an exaggerated case in order to make the reader gasp in amazement (therefore recommending the book to their friends). That does not mean, however, that you will not be amazed (nor, hopefully, does it mean that you will not recommend the book to your friends). It just means that this is one of those times when the unembellished truth is interesting and surprising enough. I don’t need to sensationalise the facts; to me, anyway, they are already sensational.

So much for what I am not saying; what I am saying is this: for many complaints and conditions, the real benefit from surgery is lower and the risks are higher than you or your surgeon think. There is a difference between any real, direct effectiveness of surgery and our perception of the effectiveness of surgery. That difference, which we will call the placebo effect, is the reason why we tend to overestimate the true effectiveness of surgery.

This brings up an important distinction that needs to be addressed now because it is central to my message. It is the distinction between observation and experiment, or between perception and reality. There is a tendency to believe what we observe (perception), even when faced with scientific experimental evidence to the contrary. For example, I observe (and perceive) the sun to be rotating around the earth; it is clear to me. But when subjected to scientific inquiry, the numbers don’t add up; the opposite must be true. And like many of the examples provided in this book, that particular belief also took a long time to shake.

When the results of observation and tradition are in conflict with the results of an experiment, what should we believe? Most people trust their own eyes – that is what got us humans so far, from the days before we had even invented science. We didn’t need randomised trials or toxicology tests to tell us which foods to eat and which ones to avoid; we worked it out by observation and tradition. But as any magician, illusionist or mind reader will tell you, we humans are pretty easy to fool, and we can all perceive, and believe, falsehoods.

BLOODLETTING, THE 3000-YEAR-OLD PLACEBO

Bloodletting provides us with a good introduction into the world of the surgical placebo because it is related to the very beginnings of surgery as a craft. It also shows us how strong the conviction of practitioners can be regarding the effectiveness of their procedures. The reasons behind the use of bloodletting as a treatment, despite its lack of effectiveness, apply to many of the other surgical practices discussed throughout this book – with the exception that this one lasted longer than all of them put together.

The story probably dates back to the Mesopotamians and Egyptians, but certainly to the Greeks and Romans. The idea was to purge the body of bad humours, or balance them, or something. (Humours were thought to be the basic substances that made up the body, and illness was thought to be due to an imbalance in those humours.) Although the initial reasons were a bit hazy, by the Middle Ages the ‘science’ around bloodletting had become very elaborate: what part of the body to bleed, what day of the week, the season, the weather and the date, and, of course, how much to take (based on further, ridiculous variables).

Bloodletting was often performed by venesection (cutting a vein), but was also done by other methods such as cutting arteries or using leeches. (In the 1830s, France imported about 40 million leeches per year for medical treatment.) It was responsible for the rise of the surgeon, or the barber-surgeon, to be precise, because they were the ones with the knives. The barbers and surgeons were the ones cutting hair, shaving, lancing boils and performing surgery, so when physicians became too important to do the bleeding themselves, they prescribed bloodletting, to be performed by the barber-surgeons using a lancet (which is how the famous medical journal got its name). The red and white poles found outside barber shops represent the bloody bandages used as a tourniquet to dilate the veins. Later, the surgeons got too important for the barbers and split away, finding new (often placebo) treatments to perform with their knives.

As more accurate diagnoses developed, like pneumonia, cancer, diabetes and jaundice, bloodletting became the treatment for all of them, partly because there was little else to offer. Also, as you will see later in the book, it was a pretty good placebo due to the fact that it was invasive, painful, drastic and shrouded in (pseudo) science.

Eventually, people started to question the effectiveness of bloodletting, and in the 1800s Pierre Charles Alexandre Louis, a French physician, published a paper using scientific methods that concluded that bleeding was ineffective in treating pneumonia. This led to protest from practitioners who ‘knew’ that it worked. One telling article from the American Academy of Sciences in 1858 stated that physicians ‘are not prepared to discard therapies validated by both tradition and their own experience on account of somebody else’s numbers’. That is pretty much what many doctors say today when you show them evidence that their treatments do not work – they’d rather rely on tradition and their own (biased) observations and continue to assume cause and effect where it does not exist (the same response that the water diviners gave when faced with the evidence).

Bloodletting gradually fell out of favour in the 19th century, partly because of increasing scepticism (and scientific reports of its lack of effectiveness) and partly because alternative placebos were springing up, like mesmerism and electricity for physicians – the latter being used to pass currents through parts of the body, usually causing muscle contractions – and an array of new procedures for surgeons. This gave doctors a way out, because, as you will see, not treating people at all is rarely an option.

Surprisingly, bloodletting was still being recommended for certain conditions in textbooks in the 20th century, including (incredibly) as a treatment for shock associated with blood loss during childbirth, and (yes, still) for pneumonia. This shows you how hard it is to kill a tradition.

THE STRUCTURE OF THIS BOOK

Chapter 1 is an introduction into the world of the placebo, with a look at what the placebo effect is and how it works. This includes a discussion on the reasons why placebos work, and how our interpretation of cause and effect can be so wrong, yet is so ingrained; how by being human, we are not necessarily being scientific. This theme is discussed further in Chapter 2, which covers some of the logical fallacies and scientific rules about evidence. This is necessary in order to demonstrate how there is ‘good’ and ‘bad’ evidence, and how the medical community often has double standards when applying scientific criticism to itself and to alternative medicine.

In Chapter 3, I have lightened the mood. We will use all of the facts out there about placebos to build the ultimate placebo, in order to illustrate how surgery fits the bill.

In Chapter 4, we put surgery to the test with examples of operations that have been tested against a placebo. You will see how commonly performed operations are often found to be useless or harmful when properly evaluated.

Chapter 5 covers history, from the earliest surgery to recent operations, looking at operations that have not stood the test of time. All of these operations were commonly performed at some stage in history, and you will see how difficult it can be to change medical practice once it becomes embedded in the body of ‘currently accepted practice’, particularly when the operation has not been subjected to the same rigorous (placebo) testing as the operations listed in the previous chapter.

In Chapter 6, I tread carefully. Given the history of failed operations that were once commonplace, I explore what operations currently being performed might be discarded in the future because of a lack of effectiveness.

In order to better understand the phenomenon that I am describing in this book, Chapter 7 explores the reasons why the system is the way it is: why new yet ineffective procedures keep popping up, why we believe in them, and why they are so hard to eradicate. I will give an overview of what is wrong with the current state of scientific medicine, and the reader will see how ethics and science are distorted in order to maintain our placebos and avoid putting them to the test. I will discuss some possible reasons why we do this, including good old human nature.

Chapter 8 was added in response to a question often put to me: ‘So what?’ Doctors have been using the placebo effect since there have been doctors; as long as people are getting better, why expose the sham? There is a lot wrong with using the placebo effect in surgery, and not just the cost and the potential harm to patients.

In the final chapter, I will offer some solutions under the title of ‘What we can do about it’, and by ‘we’ I am being ambitious by including patients, relatives, surgeons, primary care physicians, administrators, insurers, politicians, and society in general.

To reinforce many of the points I make, I use examples. Some of these examples, along with other topics worth highlighting, appear separately, in breakout boxes. My suggestion is to read them where they appear, as they have been placed to illustrate the points in the neighbouring text.

I have also added some breakout sections called ‘The patient’s perspective’, which cover common perceptions and attitudes that patients (and the general public) have regarding surgery. Having seen many patients, I have found that there are several recurring themes in what patients say, so by addressing these directly I hope to make my message more relevant to the general reader.

Readers may sense that orthopaedic surgery is overrepresented in this book. This is not because orthopaedic surgery is somehow worse than other fields of surgery; it is only because that is what I know best. I hear and read about many questionable procedures from other specialties; some of them have made it into this book and some I have not yet tackled, mainly through lack of detailed knowledge.

I have tried to minimise the use of technical medical or statistical terms, but some use is necessary in order to make the message clear. I have aimed to explain them as they occur.

It is my job to write, edit and review scientific manuscripts. In doing that, every claim must be supported by references or by the data generated in the research. Writing this book, however, is not my job – it is my hobby. I have written this on planes and in hotels, and during late nights at home. I have not included references in the body of the book because it would be distracting and off-putting in a book aimed at the general public. For those interested in the evidence behind my comments, and for those who want to explore this subject further, I have listed many references at the end of the book, grouped by chapter. All of the major studies that I refer to will be included in that section; this will allow you to look at the evidence yourself.

It should also be pointed out that I am not writing this book as a representative of any of the organisations with which I work. This includes my university, the three public and two private hospitals where I work, the various state and federal government committees I sit on, the professional societies that I belong to and their committees and boards, on which I serve. Not because they necessarily disagree with me (although some members do), but because they were not involved in the production of this book and have not seen it.

I hope you enjoy reading this book, but mostly I hope that it causes you to change the way you think about medicine, and surgery in particular. I expect the book to help you to ask the right questions and be more objective (and therefore less human) when weighing up the evidence regarding the risks and benefits of any proposed surgical procedure.

1

THE PLACEBO EFFECT

WHAT IS THE PLACEBO EFFECT AND HOW DOES IT WORK?

NEARLY EVERYBODY knows what a placebo is; the concept is fairly easy to grasp. The placebo effect, however, is a different story and will require some explanation.

Placebos, by definition, have no effect. A placebo may take any form, from a sugar pill to an elaborate procedure; as long it can not and does not have any specific therapeutic effect, it is a placebo. A lack of a specific therapeutic effect means that it doesn’t do anything to directly physically change the person in any way that might provide some improvement in their underlying condition. The killing of disease-causing bacteria by antibiotics is a specific therapeutic effect, as is the lowering of blood sugar by insulin. These are simple to understand, but, as you will find out later, sometimes we guess or make up theoretical specific therapeutic effects in order to explain the perceived response to a drug. We need to test those theoretical effects by comparing the treatment to a placebo. This concept is simple, and the process is often necessary in order to demonstrate true effectiveness. Despite the simplicity and apparent necessity of placebo tests, there is still a reluctance to put medical treatments to the placebo test, despite how often treatments actually fail that test.

Placebos can take the form of injections, operations, and other physical treatments, as long as they don’t have any specific therapeutic effect. Active placebos are also used, but they are still placebos. Active placebos have some noticeable effect on the patient, but as long as the ‘active’ component doesn’t directly affect the underlying condition, it is still a placebo. For example, a placebo pill might be used that creates tingling of the tongue, because the drug it is being tested against has such an effect. This helps with ‘blinding’ the patient, so that they cannot tell whether or not they had the placebo, but, importantly, active placebos still don’t have a direct effect on the underlying condition.

So if a placebo is inert and has no effect on the condition being treated, how then do we have something called the ‘placebo effect’? The answer lies in the fact that what is happening to our bodies on a purely physical level doesn’t correlate with our perception – how we feel. We know from some very interesting observations and experiments that our perception of our own pain, wellbeing, health and happiness is poorly correlated to the objective state of our bodies. Sometimes just having some reassurance and knowing that someone is looking out for us makes us feel better, even if the pill that the person just gave us has no active ingredients. But the problem goes deeper than that. People can be quite convinced that symptoms attributed to the specific condition being treated have improved after they have been given treatment that we know to be ineffective. There are many reasons why we might perceive ourselves to be better, which will be covered later.

The answer then, to the problem of the placebo effect lies in the difference between what is actually happening to us, and the way we perceive ourselves. It is the difference between the objective and the subjective; between any specific therapeutic effect and the perceived therapeutic effect.

However, it is not that black and white. A treatment may have some specific therapeutic effect (it may actually work on the underlying condition and physically change you) while simultaneously having some placebo effect in addition to the real effect. This added effect makes the overall perceived effect (from the patient’s point of view) greater than the real or specific effect.

By doing some adding and subtracting, you can see that the placebo effect is basically the perceived therapeutic effect, minus any specific therapeutic effect (even if there is no specific effect). The placebo effect is the extra benefit explained by the perception of improvement. To put it mathematically:

specific therapeutic effect + placebo effect = perceived therapeutic effect.

So if a drug (or any other form of treatment) is a pure placebo (no specific therapeutic effect), then the entire perceived effect will be equal to the placebo effect. The formula for this would be:

zero (specific effect) + placebo effect = perceived therapeutic effect

which is the same as saying:

perceived therapeutic effect = placebo effect.

Similarly, if a drug has a real (specific) effect on the patient, and is delivered (say) while the patient is unconscious or without their knowledge (where there cannot be a placebo effect), then the specific effect of the drug and its perceived effect (once they wake up) will be the same. In this last case, the formula would be:

specific therapeutic effect + zero (placebo effect) = perceived therapeutic effect

or:

perceived therapeutic effect = specific therapeutic effect.

This rule applies to any therapy: any treatment, whether it be a pill, a lotion, an injection, a physical treatment, psychological treatment, or an operation. And teasing out the placebo effect – the difference between the specific (real, physical, pathological) effect and the perceived effect of any given therapy – is what we will be trying to achieve, because that is how we separate what really works from what we think works.

So what are some of the placebos out there? Obviously, things that are labelled ‘placebo’ are placebos. These are drugs or devices that have been carefully manufactured so that they have no meaningful physical interaction with the body, and everybody knows that they are placebos. In reality, though, just about any treatment can have a placebo effect. In fact, treatments that are not known to be placebos can have a much stronger placebo effect. But this makes sense: if you are given a tasteless pill and told that it is a placebo, with no possibility of having any effect on you, you are not likely to feel much better after taking it.

Homeopathy provides a good example of a pure placebo. Homeopathy uses ingredients that are given in such massive dilutions that it is highly unlikely that any molecules of the original substance remain. Scientifically, the final product can have no active ingredients. Yet it is clear, if only from the fact that homeopathy is still in common use after so many years, that it has a perceived effect. It might not work for everyone, but there are people out there who swear by it – not just the practitioners. Those people think it works, even though it does not have any specific therapeutic effect.

You will see from the following chapters that the same thing applies to many surgical procedures. The difference is that the proponents of any particular operation usually have a scientific explanation to justify the treatment – one that can’t be ruled out as easily as homeopathy. However, you will also learn that a scientifically plausible explanation is no guarantee that the treatment works; it only gives an explanation as to how it might work.

Why, then, do people think that their condition has improved when nothing has happened to them, physically? There are a number of reasons, and the answer in any individual case may be a combination of these.

If we look at it logically, there are really only three reasons why someone’s condition would improve after receiving treatment that had no specific effect:

1   they did get better, but it wasn’t due to the treatment

2   they did not get better, we just think they did, or

3   they did not get better, they just think they did.

For explanation number 1, that they got better anyway, there are several explanations. The most obvious one is that most conditions are self-limiting. This is because our bodies have evolved over a pretty long time to handle most conditions that might harm us – that’s what evolution is for. It is surprising how much people underestimate the natural healing processes of the human body. My pets live long and happy lives with virtually no veterinarian involvement, yet humans apparently need constant maintenance? I don’t think so. This explanation refers to the ‘natural history’ of the condition – what happens when it is left alone. Most people who have taken antibiotics for their stubborn cold and then improved fall into this category. As Voltaire said: ‘the art of medicine consists of amusing the patient while nature cures the disease.’

For doctors, we often come to appreciate the often favourable natural history of many conditions later in our careers, after seeing what happens to the few patients who missed out on treatment or refused; we are often surprised at how well they recover.

One of the early proponents of evidence-based medicine, who was critical of accepting treatments on face value without proper scientific trials, was Archibald Cochrane, after whom the Cochrane Collaboration – the ‘mothership’ of evidence-based medicine – is named. As a prisoner of war in Germany during World War II, Cochrane was the medical officer overseeing 20 000 prisoners of war, all of whom had diarrhoea, with frequent epidemics of typhoid, diphtheria and other infections. With no medicine (except for aspirin and antacids), he expected hundreds to die. He remembers his shock at the reply from one of his captors to his request for doctors: ‘Ärtze sind überflüssig’ (doctors are superfluous). In his six months at the camp, only four prisoners died, three as a result of being shot by their captors.

On returning to Britain, Cochrane began to question many of the (then) standard medical practices, practices that were later shown to be ineffective (like bed rest after a heart attack). His observation that so much medical treatment relied on ‘amusing the patient while nature cures the disease’ led him to call for more randomised trials (which were only then starting to be used in medicine) to properly (scientifically) test ‘standard’ medical treatments.

Another reason why people get better without any treatment is a phenomenon known as ‘regression to the mean’. For example, on average (the ‘mean’), a person will have a certain number of episodes of back pain in their life, of varying severity. If you select a group of patients that currently have back pain (out of a population of average people) to test your new treatment, it is very likely that many of them will not have back pain in (say) six weeks, because they will ‘regress to the mean’. Back pain fluctuates, and selecting patients who all currently have back pain is setting yourself up to show good results with whatever you do to them because it is very unlikely that 100 per cent of them will still have back pain when you examine them later. Similarly, if you select people based on having high blood pressure at the time of selection, when you test them again later (after your treatment) their blood pressure will (on average) be closer to the mean (lower than before) because blood pressure varies each time you take it. As you can see, this can make any treatment look pretty good, and this is a particular problem in clinical research.

Daniel Kahneman refers to this phenomenon in his book Thinking Fast and Slow, in which he describes a flight instructor who considered his method of berating poorly performing pilots after an exercise to be particularly effective because they perform slightly better next time. He found this to be more effective than praising well performing pilots, because they often did worse next time. All this occurs because in a group of people (or pilots) who are repeatedly tested, there is a natural, random variation so that the performance of these people will not always be the same. If you pick those at the end of the spectrum at one point in time, they are unlikely to all remain at the end of the spectrum (among the best or the worst) on later testing. To pick those at the extremes and then attribute their fall back towards the average to your intervention is cheating – it is not proof of cause and effect. This is the same phenomenon as the often quoted underperformance of sports stars after appearing on the cover of Sports Illustrated (when they are at their peak). This is not causation – it is regression to the mean.

Regression to the mean is one of the many reasons that scientific studies of treatments should always include a ‘control’ arm – a group of patients treated exactly the same in every way except that they did not have the test treatment. Patients in a control arm can be given a placebo, or simply not given the treatment, but the presence of a control arm is the most important thing in any test of a treatment. For years, doctors have been watching patients get better and attributing the improvement to their treatment. Only the use of a control group can properly test (in the scientific sense) the effectiveness of a treatment, and placebos make the best ‘controls’.

Another reason why people improve after receiving inactive treatment is because they are receiving other treatment at the same time: concomitant treatment. This is overlooked surprisingly often in our rush to attribute cause-and-effect to any association we see.

In one scientific study of an expensive, high-tech, new, genetically engineered drug, BMP (bone morphogenetic protein – something designed to make bone) was compared to old-fashioned bone grafting (using bone taken from the patient’s own pelvis) in patients with unhealed leg (tibia, or shinbone) fractures. The results showed that both treatments, when placed between the unhealed ends of the bone, worked equally well. This was great for the manufacturers of BMP: it looked like BMP could replace bone grafting, which is painful and time-consuming. But patients in both groups also received surgery to refix their fracture; they had their tibia reamed out and had a metal rod inserted to stabilise the bone ends, a recognised treatment for unhealed fractures. This is concomitant treatment, and without a group of patients who did not receive any other intervention (or better still, a group of patients that received placebo BMP), we don’t know if either treatment (the BMP or the graft) made any difference to the healing rate – it could have all been due to the concomitant treatment. Sneaky? I think so, but most people don’t look into it that much: they just see that a scientific experiment was done, it was reported in a journal, and the results of the BMP and the bone graft treatments were similar. It was certainly good enough for the US FDA (Food and Drug Administration), who approved the drug. The drug was a massive hit for a while, but has since fallen out of favour.

The example above highlights the problem of comparative effectiveness research – comparing one treatment to another. When two treatments are shown to be equally effective, nobody considers the possibility that the two treatments are equally ineffective and that the benefit was due to something else, like concomitant treatment. Or time. I expand on this in Chapter 7.

When testing new treatments, the best way to account for things like the natural history of the disease, regression to the mean, concomitant treatment and any other reason people get better is to test it side by side against a placebo. If the only difference between your treatment group and the control group is your treatment, then any improvement in the treatment group over the control group is likely to be a result of the treatment. This difference will represent the specific therapeutic effect.

Now, to address explanation number 2: where the patients did not get better, but we (the observer or doctor) thought they did.

First of all, patients generally want to please their doctor, so if the doctor asks how the patient feels after an operation, the patient is more likely to say that they are a little better (even if they are not) than if an independent assessor asks them.

Improvement can also be manufactured simply by measuring or reporting things differently. We can measure outcomes in many different ways, and then choose to only use (report) the combination that showed improvement. By random chance, even if there was no real change in a patient’s condition, when using multiple scoring tools, surveys and measurements, some would go up and some would go down, because these things aren’t perfectly stable. Just measuring a quality of life score a few days apart can change the score up or down, even if nothing has happened to the patient. Like blood pressure, it is not exactly the same all the time; it fluctuates. Cherry-picking the outcomes that look good is called selective outcome reporting and is one way of generating a biased report.

Selective outcome reporting is common in medical research, but I believe that it is not normally deliberate; it is just human nature to see what you want to see; to sift through the data until you see what you are expecting to find, and then to use the outcome that fits your idea of what the results should be. If you believe your treatment works, you are more likely to believe the favourable results and discard the others, and then find a reason to explain why the unfavourable results might be ‘wrong’. This is called confirmation bias, which is also called ‘believing is seeing’.

Another reason why we might think the patient got better when they didn’t is because we asked the wrong questions. Doctors and patients use different criteria to judge the success of surgery, so outside the confines of a structured research study with validated, predefined outcome tools, what do we use to judge success? One common measure of surgical success, used in many specialties, is the ‘revision rate’. A revision is a second operation – a re-operation, usually required because the first one failed at some stage. In fact, many national surgical registries use revision as their main outcome in order to monitor the quality of surgery performed, often because it is a ‘hard’, objective outcome that can be reliably measured. No one would argue that this isn’t important, and this tool has been used successfully to improve surgical quality and safety, but for some, the revision rate equates to the failure rate of the surgery. Similarly, some may consider a procedure that doesn’t require revision to be a success.

Now, let’s take the patient’s perspective: other factors are also important in rating the ‘success’ of surgery, for example the degree of pain relief and improvement in function. The problem with using the revision rate in isolation as a measure of success is that it does not give the whole picture, from the patient’s perspective.

This can lead to anomalies, for example where the success of knee replacement surgery, based on the need for revision surgery, is over 95 per cent after five years, and around 99 per cent after one year. Yet the rates of ongoing pain and patient dissatisfaction one to two years after this procedure are around 10 to 25 per cent. This can lead to a mismatch in the ratings of success between surgeons or administrators and patients.

Similarly, we previously surveyed patients with limb fractures and their surgeons to measure their satisfaction with the outcome of treatment. Overall, the surgeons rated the success as much higher than the patients, and the surgeons’ ratings depended mainly on whether or not the bone healed. Patient satisfaction, on the other hand, was unrelated to fracture healing or the need for further surgery, and depended on factors such as whether or not they were able to return to work.

In general, surgeons tend to dwell on the technical aspects of surgery (what the X-rays looks like, the amount of tumour removed, the restoration of blood flow and the avoidance of complications, for example). These may be relevant, but they are not necessarily aligned with a measurable clinical benefit for the patient (relief of pain, prolonged survival, etc.). In spine surgery, for example, the success of a spine fusion (to fuse two vertebrae together) may be measured by surgeons according to whether the two bones successfully fuse. To the patient, however, this event may not correlate with their level of pain relief or functional improvement. In fracture surgery, many studies measure the time to see healing on an X-ray – a measure of little concern to the patients and only loosely related to pain or function.

If we are going to measure the results (success rate) of surgery, you can see that we should be using independently measured, patient-relevant, validated measurement tools. Asking a surgeon about their success rate might give you a completely different answer.

That covers the situation where the patient did not get better but we thought they did. Finally, we come to explanation number 3, where the patient did not (really) improve but they think they did.

There are many reasons why patients might think they get better. Firstly, if they expected to get better, they will look for confirming signs to fit their belief. Psychologically, patients will work to overcome the feeling of continued symptoms if they underwent treatment that was expected to result in an improvement. If they expected an improvement and it didn’t arise, they would look for signs that it might have improved some things, and concentrate on those things, much like the researcher concentrating on the favourable findings and discounting the information that doesn’t fit with their expectations. This is supported by research around placebos where greater expectation of success leads to greater success – but this is the topic of the next chapter.

It should be noted that the placebo effect can be strong enough that it can override harmful specific effects of treatment. All of the factors contributing to the perceived benefit of treatment may be strong enough to support treatment that actually causes harm. This makes sense, because the overall perceived effect is really just the addition of any direct (specific) effect and the indirect (placebo) effect. If the placebo effect is sufficiently positive, it can more than make up for small or moderate negative specific effects, so that the sum of both effects is still positive.

Certainly, surgery has some negative effects. It causes pain and exposes patients to other risks and discomforts. If the positive direct effects of a truly effective operation can lead patients to feel an overall benefit, then so can the indirect, placebo effects.

In this chapter we have learned that a placebo has no specific, direct effect on the underlying condition being treated, although it can have effects on the patient’s perception. Treatments that do have a specific (true) effect on the underlying condition can also have a placebo effect.

The placebo effect however, is the perceived or measured effect beyond that of any specific effect.

To recap, there are several reasons for a placebo effect: the patient may have improved anyway (natural history, regression to the mean, concomitant treatment, etc.) or the improvement was only perceived by the patient (through psychological or indirect physiological mechanisms) or perceived by the observer (biased observer, selective reporting, measurement error, etc.).

I will persist with this definition of the placebo effect (any effect that contributes to the total perceived effect, beyond the specific effect of the treatment), even though I have described other reasons (that is, reasons other than the placebo) for the extra effect seen with placebos, such as the natural history of the condition. I have chosen to do so because it is easy to understand, and because that is how many people understand it. I accept that the excess benefit seen is not directly due to the placebo, and this is where confusion can arise between the placebo (which has no effect), and the placebo effect. This is why this excess effect (beyond the true effect) has been labelled a ‘meaning response’ rather than a placebo effect. For a full explanation of this concept, I refer you to Daniel Moerman’s book Meaning, Medicine and the Placebo Effect.

One problem with using the term ‘placebo effect’ to describe an effect that is not necessarily due to the placebo treatment is that treatments are often justified based on this ‘effect’. This is addressed in Chapter 8.

Now that we have a basic understanding of the placebo effect, let’s see how this fits with the science of medicine.

2

THE SCIENCE OF MEDICINE – OR LACK OF IT

WHAT MAKES ‘GOOD’ EVIDENCE?

THE TENDENCY FOR human beings to attribute cause to an effect when they see one thing follow another is hardwired. It is not at all scientific, but it is very human. To be a human trait it does not need to be logical – it needs to help our survival and give us an evolutionary advantage. If we eat a new kind of fruit, and then get sick, we will avoid this fruit in the future. Our brain doesn’t really care if the fruit caused the illness or if it was a coincidence, or if only that particular piece of fruit was bad; if there are alternatives, the brain doesn’t want us to waste our time on any experiments to find out. Maybe if you ran out of food you might try that type of fruit again; otherwise, your brain will tell you to steer clear and stop wasting its time. That might not be scientific, but it is an efficient use of time and resources, and it is low risk. It is also Olympic-grade conclusion jumping.

Humans are very prone to this common logical fallacy, called post hoc, ergo propter hoc: ‘It follows, therefore it is because of ’. And it is very hard to shake. My sister is over fifty years old and has not eaten a doughnut since she was a child, when she fell ill after eating one. Because she can eat cake, and all the ingredients of a doughnut individually, without any problems, her continued avoidance of them makes no sense, and she understands that, but she still doesn’t want to eat one; they make her sick.

So you can see that when people feel better after being treated, they will attribute their improvement to that treatment, despite all of the other reasons that might explain the improvement (see the previous chapter). This jump from an observed association between two events and the perception of causation is human nature. This is the explanation behind the large number of recommended treatments for things like the common cold, or hiccoughs: whatever treatment you give, it will appear to work every time.

As mentioned previously, the way to measure the true (specific) effect of any treatment (let’s call it treatment A) is by comparing it to a control. By having two groups of patients, one group receiving treatment A and another group of similar people being treated identically, except without treatment A, we have a way of allowing for many of the problems caused by patients getting better anyway.

However, unless the patients and the researchers are ‘blinded’ to which group is getting what treatment, other biases (errors that skew the results of a study) can creep in. Without blinding, the active treatment group (those receiving treatment A) in a study can get a boost from the placebo effect (for example, from the expectation of improvement, from both the patient and the doctor), whereas the unblinded control group (who did not receive treatment A) won’t get that boost because they won’t be expecting to get better and they won’t be looking for signs that they are.

The use of a control group in a test of a treatment, the systematic measurement of variables associated with the participants, and the statistical analysis of the results to compare the two groups is called an experiment. It is a scientific way of testing a hypothesis. It reduces the biases (errors) that are present in non-experimental (observational) studies.

Bias is simply a skewing of the results; a deviation away from the truth in one particular direction. Biases will tend to skew the results of a study towards what we expect or want them to be. Biases may affect the results of any study. There are many types of bias and some are more important (more likely to influence the results) than others. Firstly, selection bias can occur when the patients in the active group are different to patients in the control group. For example, one group might contain more smokers, or more men; the patients might be older, or have more severe disease or symptoms than those in the other group. These factors might influence the results, and an imbalance of these factors between the groups might explain some or all of the differences seen, making the treatment seem more (or less) effective than it really is.

Apart from making sure the two groups are similar, you also have to make sure that the patients in each group are actually treated identically; that some aren’t receiving some other treatment as well. And every variable that is measured should be measured without bias, especially the main outcome variable, which should be measured by an independent observer (not, for example, by the surgeon who did the procedure).

Just because we use an experimental design, and compare our active treatment group to a control group, that doesn’t mean we have avoided bias altogether. Experimental studies vary in their bias; there are good studies and not so good studies. There are tools to measure how biased a study might be (such as the Risk of Bias tool used by the Cochrane Collaboration) which may be used as a measure of study quality.

THE BEST WAYS TO MINIMISE BIAS

Placebo control

Using a placebo treatment for the control group gets rid of many potential biases, as the perception of the patient and the researcher are not influenced by what they expect to see. This is particularly important when the outcome is subjective: something like pain or mood. If you are measuring something purely objective, like mortality (death) or something that can be determined via a blood test, it is less important to use a placebo.

Using a placebo is a way of blinding a patient (and those around them) to which group they are in, and, through mimicking the processes of the active treatment (injections, for example), placebos are also a good way of treating the control group exactly the same way as the active group, except for the actual ingredient that you are testing.

There is a concern that many physical treatments cannot be substituted with a placebo, but placebos have been used for surgery, physical therapy, acupuncture and many other physical treatments.

Randomisation

Randomly assigning the patients to the two treatment groups removes any bias that might exist by selecting certain types of patients more frequently in one group compared to the other. It is also important that the randomisation be concealed, so that the researcher doesn’t know what treatment the next patient will get, otherwise they might not enter them onto the study, or use other methods to bias the results, like change the order in which patients are recruited in order to make the active treatment look better.

Randomisation doesn’t always give you perfectly even groups, however, so you need to check this when you look at the characteristics of the patients in each group. Because random allocation might (by chance) result in the two groups being different, other techniques have been used to keep the allocation of patients relatively random (and concealed), while at the same time minimising any important differences between them.

Blinding

If the patient or the person measuring the outcome knows what treatment was given, their own biases creep in to the measurement of the outcome. Where possible, everybody (the patient, their friends, hospital staff, the treating doctor, all the researchers and the person measuring the outcome) should be blinded to the treatment group. The best studies will even blind the statistician until they have finished the analysis. Yes, even statistics is not as black and white as you might think and is open to bias in the assumptions, tests and variables that are used and the way they are reported. See ‘Manufacturing significance’ later in this chapter (page 46) for more on this.

Ideally, the whole study is performed from start to finish and the results are written up before anybody knows which group had which treatment. Good studies also include a test of blinding, where they ask the patients whether they thought they got the real treatment or the placebo. If the patients can’t pick what group they were in, it is a good sign that blinding was successful.

Analysis and reporting

There are many biases that can creep into the analysis of the results, not just in the statistics. Often researchers will measure many different outcomes, but only report the ones that show the treatment to be effective. On a larger scale, many studies might be commissioned, and only the positive ones published. There are many ways to make your study show you what you think it should. It used to be said that you could torture the data (by using different types of statistical tests, under varying assumptions) until it confessed to your version of the truth – but it isn’t like that. All you need to do is subconsciously wish it to be true and you will subconsciously, through the many small decisions you make during the experiment, bias the results towards showing what you expect or wish. This is partly shown by evidence of ‘p-value hacking’ where statistical tests and reporting are skewed to come up with a statistically significant p value (showing that the probability of obtaining the results by chance is very low, and therefore concluding that your treatment caused the results). A good example of this is given in the section ‘Manufacturing significance’, below. First, though, you should understand the principles of what researchers call ‘significance’, which is shorthand for ‘statistical significance’.

STATISTICAL SIGNIFICANCE

In the world of science we test things, and make conclusions based on the results of those tests. From this, knowledge is gained, which informs future developments and tests (experiments).

The things we test are hypotheses, and our decision to accept or reject a hypothesis is based on the likelihood that the results would have occurred by pure chance (if our test treatment had no effect). For example, if an experimental finding (the effect of our treatment) is highly unlikely to have occurred by chance (say there’s a one in 100 000 chance of that), then we would reject the ‘null hypothesis’ (that the treatment is not effective), and attribute the finding to whatever it was we were testing: the treatment, the new drug, the operation or whatever – how else would we explain those improbable results, particularly if we have a good experiment that has controlled for all the other factors that may have influenced the results?

If we are going to make decisions about rejecting hypotheses or not, we need a pre-defined probability cut-off – a point beyond which we will conclude that the probability of the results occurring by chance are too low, and that the results are therefore due to the treatment we are testing. This is usually set at a probability of p = 0.05 (a 5 per cent, or one in twenty, chance). If the results are less than 5 per cent likely to have occurred by chance, we say that they weren’t due to chance – that they were due to our wonder drug (or whatever it is we were testing). This cut-off is the ‘significance’ level, beyond which (less than 0.05) we can claim statistical significance.

This method of decision making is so important that in the academic world, when you use the word ‘significant’, it means statistical significance, usually at a threshold of 0.05. And statistical significance is what we are all after. Finding a ‘p value’ of 0.1 from your statistical test usually leads to disappointment, and a p value of 0.50, or 50 per cent (say) means that you need to get back to the drawing board because your treatment probably doesn’t work (as your results had a 50:50 chance of occurring if your treatment did absolutely nothing). Basically, a p value of less than 0.05 is news.

Furthermore, your paper will not be seen as important, innovative or any kind of discovery, and it is less likely to be published (or even submitted for publication) if your p value is not <0.05. The failure to reach significance is not really a failure, it’s just an objective result, but you can see how some people would consider it to be such.

It should be noted that achieving a p value of less than 0.05 does not necessarily mean that your treatment worked. Even if the treatment has no effect, you will still reach statistical significance 5 per cent of the time (by definition) by chance alone. This is part of both the beauty and the frustration inherent in science: it is never 100 per cent certain and rarely proves things – it is based on probabilities and levels of uncertainty.

Manufacturing significance

What if I could produce an experiment that concluded that listening to an old song could make you younger? Not feel younger, but be younger. Impossible, of course, but the study reported below shows not only how it is possible to show this, but also how easy it is to produce statistically significant, supportive evidence, not by torturing the data until it tells you what you want, but by gently massaging the data into the shape that you want or expect it to form. Manufacturing significance in this ‘gentle’ way is easy, and those who base their decisions on scientific findings need to be aware of this problem.

P-hacking, also known as data-dredging, fishing or significance-chasing, means exploiting the flexibility inherent in any research in order to arrive at a different result (with different p values), and then choosing to report only the significant result and the method you used to achieve that particular result; the rest is swept under the carpet (or subconsciously considered erroneous), and what you present to the world (what you publish) is a neat single analysis of your neat data set, and a significant result with a p value of less than 0.05.

In this study, researchers set up two experiments that they actually performed on students at the University of Pennsylvania.

The study investigated whether listening to a song about older age makes people actually younger. (Note: this is clearly impossible, but that’s what makes it brilliant.)

We asked 20 [students] to listen to either ‘When I’m Sixty-Four’ by The Beatles, or ‘Kalimba’. Then, in an ostensibly unrelated task, they indicated their birth date and their father’s age. We used father’s age to control for baseline age across participants.

According to their birth dates, people were nearly a year-and-a-half younger after listening to ‘When I’m Sixty-Four’ (adjusted mean = 20.1 years) rather than to ‘Kalimba’ (adjusted mean = 21.5 years), p = .04.

Now, bear with me for a moment. Note that they used father’s age to control for age, instead of real age. This is important, and is a reasonable way of working out how old (on average) a group of people are. For example, if the average father’s age of people in group 1 was 40, and that of group 2 was 50, the people in group 2 would ( on average) be about 10 years older than the people in group 1.

Everything they did could be considered reasonable in a scientific study of this type. Their point is that there are too many ‘researcher degrees of freedom’. That means that there are too many ways in which they can influence the outcome. Having so many ‘degrees of freedom’ generates many possible outcomes, and increases the probability of finding the outcome you want (or expect) by chance alone, among so many different analyses. Two of those degrees of freedom (flexibilities) are:

1   ‘Flexible’ sample size: The authors recruited twenty participants, and then ran the tests. They then planned to add another ten participants if the study didn’t show what they expected, and test it again. That doesn’t sound like much, but this is really two separate analyses, two bites at the cherry, increasing the chance of a wrong (false positive) result occurring by chance.

2   Adding variables: The authors actually had the patients listen to a third song (not reported), ‘Hot Potato’. Adding another variable meant there were more ways to analyse the data, this time tripling the chances of getting a ‘false positive’ result.

They also recorded many other variables to determine age (not just father’s age), thereby vastly increasing their chances of getting the result they wanted by chance alone.

The fully reported results are given below. Here, the authors explain what really went on behind the scenes. The original report is now in bold text. The rest is the added information that allows detection of the bias in the methods. This full reporting is what should occur in scientific papers.

We asked 20 34 University of Pennsylvania undergraduates to listen only to either ‘When I’m Sixty-Four’ by The Beatles or ‘Kalimba’ or ‘Hot Potato’ by the Wiggles. We conducted our analyses after every session of approximately 10 participants; we did not decide in advance when to terminate data collection. Then, in an ostensibly unrelated task, they indicated only their birth date (mm/dd/yyyy) and how old they felt, how much they would enjoy eating at a diner, the square root of 100, their agreement with ‘computers are complicated machines,’ their father’s age, their mother’s age, whether they would take advantage of an early-bird special, their political orientation, which of four Canadian quarterbacks they believed won an award, how often they refer to the past as ‘the good old days,’ and their gender. We used father’s age to control for variation in baseline age across participants.

According to their birth dates, people were nearly a year-and-a-half younger after listening to ‘When I’m Sixty-Four’ (adjusted mean = 20.1 years) rather than to ‘Kalimba’ (adjusted mean = 21.5 years), p = .040. Without controlling for father’s age, the age difference was smaller and did not reach significance (means = 20.3 and 21.2, respectively) p = .33.

They ran a simulation of studies to determine the effect of adding a variable, adding a covariate, running three different analyses instead of two, and adding ten more patients to their sample size of twenty. They found that if you did all four of these seemingly harmless things, the chance of getting a p value of less than 0.05 when there is no real effect was about 61 per cent.

Without making up data (which is fraud), just by playing around with the analysis, it is very easy to generate a statistically significant result (something seemingly unlikely to have occurred by chance, and therefore supporting the treatment), even when the treatment had no effect. It would be even easier, if the treatment had a small effect, to make it look more effective than it is. The answer to this problem is to have honest and complete reporting of every variable used, all assumptions made, data excluded and analyses performed. And for scientists to realise their own biases.

LACK OF REPRODUCIBILITY

One of the fundamental principles of science is that the results of any experiment should be reproducible. The kind of ‘sloppy’ science referred to above is a major reason why so many medical studies are not reproducible, and this undermines our ability to rely on scientific findings. The lack of reproducibility in many scientific findings is worrying and has even led to branches of medical research being founded on false study findings that were never reproduced (that is, never checked). This phenomenon has been recognised in studies such as ‘Why most published research findings are false’ by John Ioannidis.

Reproducibility is essential because it means that the results can be relied upon, as they are more likely to be true. Currently, many studies are not repeated and many findings stand alone, without verification from separate, independent researchers. This is a problem because often when studies are replicated, they fail to reproduce the original findings.

To get the replication/reproduction terminology clear from the start, I will refer to replicating or repeating studies (doing the same research again, preferably independently), and whether or not the replicated study reproduces the same results.

From the definitions above, two problems are apparent: firstly, studies are often not being replicated, and secondly, when they are being replicated, they often fail to reproduce the results of the initial study. Follow me so far?

The good and the bad

Reproduction of previous results is a good thing: it is a verification of the findings of previous research, therefore increasing the probability that those findings are true.

Failure of the replication study to reproduce the original results decreases the probability that the original findings were true. This is bad for the original researchers, but it is good for everyone else because it is science’s way of detecting errors – of self-correcting.

Failure to replicate studies (at all) is bad for everyone, because it means that we are less certain that the original results are true, and we could end up holding onto to false beliefs for a long time, and therefore using ineffective treatments.

Falsifiability

According to Karl Popper, it is a basic tenet of science that any finding/statement/theory must be falsifiable. If something cannot be disproved, then, in effect, it cannot be challenged and becomes dogma, not science. A study or theory that stands up to attempts to falsify it is a more robust one.

Reproducibility

Replicating studies goes hand in hand with falsifiability. If nobody is going to repeat a study (and attempt to falsify it), then it doesn’t matter if it is falsifiable or not. Being falsifiable is not enough: theories gain strength from standing up to attempts at falsification, and study findings need to be reproduced if they are to be relied upon. As the theoretical physicist Wolfgang Pauli put it, ‘If they can’t be reproduced, then the conclusions of a study are not only not right, they are not even wrong.’

Some examples

An article in the journal Nature from 2012 reported an attempt by researchers to replicate fifty-three landmark or breakthrough papers in the field of pre-clinical cancer research. Despite multiple attempts at reproducing the findings in their own lab, they could only reproduce the findings of 6 out of the 53 studies. They even went to the extent of contacting the original authors and repeating the studies in slightly different ways.

In one case, when told that despite replicating the original research fifty times, the original findings were not able to be reproduced, the author of the original paper said that he was not surprised, as he had done the experiment six times himself, and only produced the interesting findings once. That means that the original researchers could not even reproduce their own findings in their own labs, yet they only reported the one positive study, not the negative studies. Depending on how they did it, that is either selective reporting bias or publication bias, but either way it is biased.

Worryingly, several of the non-reproducible studies had already spawned new fields of research that were founded on the original findings, yet never validated them through retesting.

Lamenting the declining success rate of clinical trials and a widening gap between discoveries that were ‘interesting’ and those that were ‘feasible’, a team from Bayer replicated sixty-seven published in-house projects and could only reproduce the original findings in about 20–25 per cent.

Both these papers blame sloppy science by the researchers, and the academic system, which rewards interesting findings.

A 2005 review looked at the biggest articles (articles with the highest number of citations) in three major general medical journals and found that most of them were either not replicated (24 per cent) or were replicated, but the results were not reproduced (no effect, 16 per cent; lesser effect, 16 per cent).

In a more recent paper, researchers looked at ten years of publications in one journal and found that when studies were performed on current accepted treatments, they were more likely to show them to be ineffective or inferior to previous treatments than to support their continued use.

In a recent review of medical publications testing standards of care, it was found that such studies were more likely to refute the original findings than reaffirm them. Interestingly, this reproduced the findings of previous research.

Why is there a lack of repeat studies?

Unfortunately, there is a perception that only ‘novel’ science is rewarding. This may be true, as novel science is rewarded with grant money, promotions, doctorates and fame. Who wants to do a study that someone else has already done, and do it exactly the same way? Yet that is the only way we can confirm if those interesting studies that pop up every now and then are true.

THE SOLUTION

Firstly, scientists need to be more scientific; a lot of this is sloppy science. The methodology needs to be better, and studies need to have explicit protocols published prior to the research starting.

Secondly, there need to be more journals that publish completely and with open access, and choose what they publish purely on the basis of scientific merit, not newsworthiness or novelty.

Thirdly, funders (grant funders, industry, universities, governments) need to appropriately prioritise replication research, particularly of important findings that have significant clinical and resource implications, instead of discounting such research as not being ‘innovative’.

MEDIA PERCEPTION OF SCIENCE

The over-representation of good news from medicine is a problem in the scientific literature, but that bias is magnified manifold in the media. I have seen media reports of supposed cures for such things as cancer, dementia and paraplegia. And the more advanced the science seems to be, the more the media love it. In the surgical field, there are many examples; robotic surgery is just one of them.

Our research team searched the highest circulation newspapers in Australia for articles using the words ‘robotic surgery’. We got hundreds of articles and most of them were positive towards the results or the potential results of using robotic surgery. Words like ‘revolutionary’, ‘science fiction’ and ‘advance’ were often used. You can replicate this research yourself if you like.

The media reports stand in contrast to the scientific facts, where study after study, and summaries of those studies, have shown that robotic surgery does not provide any significant improvements for patients over standard surgery. It may be associated with complications and it certainly costs more. Surgeons love it because it is technologically advanced and expensive and holds promise – it just doesn’t actually help anyone.

This media misrepresentation is not necessarily the cause of our overestimation of the effectiveness of surgery, but it is a sign of our love for science and our wish for new breakthroughs in medicine that help people. Science (and medicine in particular) is the good news story of the last few decades, and stories about surgeons wasting time and resources, and charging for things that are not of any benefit, do not sell papers.

Fourthly, the readers of the research need to be aware of the problem, and they need to equip themselves with the tools for determining scientific validity, and start using those tools.

The problem has been brought into the limelight over recent years, and many government and academic groups are attempting to address it. In surgery, however, we have trouble getting the research done in the first place, let alone repeating the studies.

WHERE DOES SURGERY FIT IN?

If highly regulated studies using medicine and lab animals are not reproducible due to biases in conduct and reporting, what are the chances that surgical studies might also be biased? Our research group has looked at the quality of surgical studies, including randomised trials and systematic reviews (of many randomised trials on a particular topic). The good news is that even though the standard is often not high, with studies often failing to meet many quality benchmarks, the overall standard is probably not a whole lot worse than in other (non-surgical) areas of medicine.

In essence, our (and the patients’) enthusiasm to see the treatment work can bias the results in many ways. There have been many articles and research papers written on bias in the medical literature, yet it remains underappreciated by many doctors and possibly most surgeons. We should always take this bias into consideration when we read medical articles, not just because of the methodological biases that I have mentioned, but for many other reasons. For example, you should be sceptical of favourable study results that come from someone who has a reason to be very positive about the treatment (such as the company that sells it or the doctor who invented it). Industry sponsorship of research, for example, has been associated with better results than non-sponsored studies for various treatments, including surgical procedures.

Another bias that tends to make treatments look better is publication bias, where inconclusive or negative studies are not published (often because they are never submitted to a journal) and the exciting and positive studies tend to make it to press. This means that any summary looking at the overall effectiveness of that treatment is not getting the full picture, and the summary estimate of effect will be inflated by the overrepresentation of positive studies.

Potential biases in research are important, so in order to get any new drug on the market, it has to be tested in a rigorous scientific study, preferably against a placebo, but often against the current treatment. These studies are picked apart by scientists in order to make sure that the new treatment is genuinely beneficial. It takes years to get new drugs to market, and a lot of money.

How does surgery fit into this highly regulated and rigorous environment? The answer is that it doesn’t. At the Federal Drug Administration in the US, and in similar bodies worldwide, surgical procedures are left out. There is no need to test a surgical procedure against anything, let alone in an experimental study, before using it. At some stage the procedure comes into fashion and then it becomes mainstream, making it hard to subject patients to a randomised trial, usually on the grounds that it is unethical – as if the introduction of an untested procedure was ethical in the first place!

There is an example I like to use, because the procedure was thought to be so effective that a proponent wrote an article in a scientific journal stating that the (then) proposed trial comparing it to non-operative treatment was not necessary. I like it because he used the parachute analogy, and because he was wrong.

The parachute analogy states that you don’t need to perform a randomised trial to tell you that a parachute works, implying that the treatment under discussion is so obviously effective that a trial is unnecessary. It is an example of ‘argument by analogy’ and also reduction ad absurdum: taking the comparison to an extreme. If there was ever an operation that saved every life, and where everybody treated without the operation died, I would agree – in that case, you wouldn’t need a randomised trial – but this is very rare.

Invoking the parachute analogy

A leading thoracic surgeon published good results in a series of patients who had undergone a new operation for emphysema (a common lung condition), which involved removing 20–30 per cent of each lung (lung volume reduction surgery, or LVRS).

The operation became popular and was being performed fairly widely, but due to persisting doubts regarding effectiveness, a large randomised trial to compare LVRS to medical (non-surgical) therapy (the NETT trial – National Emphysema Treatment Trial) was proposed, and funded by Medicare, the National Institute of Health and the Agency for Healthcare Research and Quality in the US.

The surgeon then used the parachute analogy in an editorial in which he stated that the evidence of benefit from LVRS was so overwhelming and obvious that the NETT trial was not needed.

In fact, great results were still being published from (uncontrolled) case series in the same year that the results of the NETT trial were published in the New England Journal of Medicine. The trial showed no difference in the rate of death between the two groups at two years. The topic has been covered in a Cochrane review of eight studies where they also note that there is no difference in deaths at two years. There was an improvement in lung function and quality of life in the surgical group over that two-year period, but this can be partly explained by the fact that surgery tended to weed out the sicker patients early: the death rate by two years was the same, but the odds of dying early (within ninety days) was more than six times higher with surgery.

Newer is not necessarily better

I have seen many new operations introduced over the years without any good evidence that they are effective, or better than the alternatives. This can often occur on a small scale, like changes to the way we do a procedure, or using different equipment.

Total hip replacement surgery for arthritis is generally considered a very effective operation in achieving pain relief and restoring function, even though it has never been subjected to a randomised trial. Within the practice of hip replacement surgery, however, there is a lot of variation. When I was a junior doctor, the standard (indeed, the only) hip replacement involved cementing the prosthesis (the replacement) into the thigh bone. Since then, because hip replacements aren’t perfect, and they loosen and wear, surgeons have been trying to make a better hip replacement. I have seen this evolve over thirty years and it is still evolving. When I was an intern, ‘uncemented’ implants were introduced in order to tackle the problem of loosening and bone resorption (where the bone is eaten away) – so called ‘cement disease’. The first ‘uncemented’ hip replacements were used for many years, but it took many more years to realise that they were inferior to the previous, cemented hips. It turned out that the problem was not the cement at all – it was the polyethylene particles from the surface of the artificial joint. Surgeons just thought it was the cement, and it became a self-fulfilling prophecy.

Cement is still frequently used in hip and knee replacements today. Back then, though, nobody that I knew thought to compare the new hips to the old ones in a scientific trial; they had their reasons to justify their decision (based on a biologically plausible theory – more on that later), and they went for it. They were surgeons after all, so they surged.

Hip replacements have been around for about fifty years and millions have been implanted. It is a costeffective procedure and many patients have had the pain and stiffness of arthritis relieved by this procedure. The following is just a single case in point of the fallacy of new-is-better; it is the case of a certain metal-on-metal hip.

Widespread uptake of hip replacement surgery began after pioneering work by Sir John Charnley in the UK. After testing several techniques and materials for the bearing surface of the ball and socket joint, he settled on ‘metal on poly’ – a metal ball (and stem) that articulates with a plastic (high density polyethylene – ‘poly’) socket. Although there have been modifications along the way, metal-on-poly is still the gold standard today and by far the most common type of hip replacement used. It is the only type I use.

In 2005, a device manufacturer introduced a new metal-on-metal (MoM) hip replacement.

MoM hips actually pre-date metal-on-poly, but the originals from the 1950s were a failure. Refinements in engineering saw MoM hips relaunched in the 1990s, and this particular one was a ‘me-too’ implant, as another MoM hip had already been released and was gaining popularity. The idea is that MoM hips should last longer, because the poly in metal-on-poly hips eventually wears out (although only by millimetres over decades, and newer types of poly wear out even more slowly). Without any long-term results from headto-head trials, the new MoM hips were approved and introduced. They were mainly used in younger patients, where the benefits of implant longevity were thought to be greatest.

Yet there was never (and has never been) any good evidence supporting this MoM hip over standard metal-on-poly hips; it just sounded better.

The problem with MoM hips was the problem with so many other things in medicine: it sounded good, but was never properly tested in people. When surgeons do things that are not properly supported by comparative studies, they rely on what I call the ‘wobbly tripod’ of evidence (see Chapter 7). The tripod consists of: 1) biological plausibility (in this case, metal is harder than plastic, so it will not wear out as fast); 2) non-clinical evidence (in this case, metal didn’t wear out as fast in the lab – a completely artificial and far-removed substitute for what happens in a live, human hip), and; 3) personal experience (it seemed to work, at least in the short term, which, of course, wasn’t the point).

And so MoM hips were used widely in many countries, on tens of thousands of patients. What happened? Well, they didn’t wear out; there wasn’t time for them to wear out because of all the other things that went wrong with them first. What happened is what often happens with something that sounds good on a superficial level: unintended consequences.

Even the little friction that was present in the design was enough to release metal ions into the body. Unusual reactions to the metal led to pain and implant loosening from a type of immune response. There were also reports of systemic complications. There have been other problems reported from MoM implants. A good summary of the problems with MoM hips and some timelines are provided in a British Medical Journal article from 2012 listed in the references for this chapter.

The failure rate was reported as unacceptably high in some joint replacement registries, like the Australian Orthopaedic Association National Joint Replacement Registry, from as early as 2007. It was withdrawn from the market in Australia by the regulators in 2009 because of the consistently high failure rate, but it continued to be used in the US. The company eventually recalled the implant itself in August 2010. In the meantime, they were paying influential surgeons (‘thought leaders’) millions of dollars. Not surprisingly, these thought leaders were protesting that the hip was fine; surgeons just weren’t using it properly. One surgeon in particular wrote articles supporting the MoM hips, and defended their use at meetings where the audience was not always aware that he had received $3 million from the company that produced the hip.

So how did it happen? A full analysis of the relative roles of industry, regulators, surgeons and patients is beyond the scope of this book, and the legal battles and payouts are still going, but the main reason that this happened is because everybody (industry, regulators and surgeons) thought this implant worked, when there was insufficient evidence that they did.

I have no problem with surgeons trying new things, and many advances have been made by surgeons doing exactly that, but is it really asking too much to insist that the introduction of new technologies be limited until their effectiveness has been established, perhaps by allowing early use, but only within registries or controlled trials?

° ° °

We have seen in this chapter that improving the methodological quality of a scientific experiment (like a clinical trial) increases the likelihood of the result being an accurate (unbiased) estimate of the truth. The pervasiveness of biases and sloppy science has led to a problem with the validity of scientific studies that has led to a general overestimation of the effectiveness of the treatments being tested. Just like randomising patients into comparative treatment groups, and blinding of patients, doctors and statisticians, placebos have an important role in improving the quality (reducing bias) in any scientific test of treatment, particularly if the measured outcome is subjective.

Now that we know how important placebos and ‘controlled’ trials are in science, and how placebos have their effect – by relying on our perception of the effectiveness of the treatment – we can look at what factors influence the placebo effect. In doing so, we can build the ultimate placebo and see how surgery might fit that mould.

3

BUILDING THE PERFECT PLACEBO

WHAT MAKES A GOOD PLACEBO?

For a placebo to work, the patient has to believe that it will (or at least should) work. Being given a tasteless pill and told that it has no effect whatsoever will not make you feel any better, so the first step in building the perfect placebo is to disguise it as something that works. This is why the placebo effect in everyday practice is much greater than the effect seen in clinical trials, where the patient at least suspects that they might be getting a placebo.

There are many examples of treatments that have quite good results in observational (non-experimental) studies but when used in a placebo-controlled trial the effectiveness is much less, or disappears altogether. One famous example is hormone replacement therapy.

Once commonly prescribed for post-menopausal women, hormone replacement therapy (HRT) was thought to decrease the chance of cardiovascular problems like heart attack and stroke. This made sense, because the risk of these conditions in women went up suddenly after menopause, indicating that the naturally circulating hormones may have been providing a ‘protective’ effect. Many large observational studies supported the belief that HRT after menopause lowered the risk of cardiovascular complications. In fact, in a summary of the observational (non-randomised, non-placebo) studies from 1991 it was estimated that HRT halved the risk of cardiovascular disease.

However, large-scale placebo-controlled studies (mainly the Women’s Health Initiative, a large US trial) showed no decrease in heart attacks, but instead an increase in strokes, deep venous thrombosis (clots in the deep veins of the body, usually in the leg) and breast cancer with HRT. The release of this evidence in the early 2000s led to a dramatic decrease in the use of HRT.

It has been suggested that the observational studies may have been confounded (biased) because healthier women tended to be prescribed HRT (so they made the results of the HRT look better), and possibly because physicians were less likely to prescribe HRT to women at high risk of cardiovascular disease (making the non-HRT group look worse).

There is ongoing debate about the role of dosages, types of HRT, and how soon after menopause the treatment is started, in explaining the mismatch between the placebo studies and the observational studies, but the bottom line is that the beneficial effects of HRT were overestimated by the observational studies.

In this case, the differences between the observational studies and the controlled experiments (using placebos) is not due to the placebo effect; it is due to the bias that is inherent in non-controlled studies. However, when this type of bias leads to the apparent effectiveness of a treatment, it is often labelled a placebo effect.

Good clinical trials will test to see whether the blinding worked. The patients are asked, at the end of the study, which treatment they think they received. If their guesses are no better than chance, then good blinding has been achieved. Interestingly, in placebo studies, patients who thought they got the active treatment do a lot better than those that thought they got the placebo, regardless of what they actually received. This provides further evidence that you need the patient to believe that the treatment is effective in order to make it work. Expectations influence outcomes such that belief in effectiveness becomes a self-fulfilling prophecy.

MORE IS BETTER

What about the placebo itself? For a start, a good general rule is that more is better: bigger in size, cost, complexity, invasiveness and patient involvement. Let’s start small and build it up. If you’re giving a placebo pill, coloured pills work better, but the effectiveness of the colour depends on what you are trying to achieve. You also need to give lots of pills – the more you prescribe, the greater the effect. Preferably, the pill will be expensive, or the patient should at least believe that it is expensive. For example, in a study testing two groups of volunteers with the same placebo, they found the most effective placebo (85 per cent effective, versus 61 per cent) was the one used in patients who were led to believe that it cost $2.50 per pill, compared to the group that thought it cost $0.10 per pill.

Size and dose are only part of the story. The name of the pill also influences how effective it is. If you don’t believe that, ask any advertiser.

You can even make the pill more ‘active’. This can be done by, for example, giving the pill a taste, so that the patient thinks that they are getting the real treatment (raising expectations). Active placebos that have some of the side effects (but not the main therapeutic effect) of anti-depressants have been shown to be more effective than ‘inert’ placebos, because they provide effects that are very close to the anti-depressants themselves. They help by making the patient think that they have taken the active drug and by better blinding the patients.

The confidence and language of the administering physician is also important in improving the response to a placebo treatment. Having a confident and enthusiastic doctor with a positive attitude, instead of a ‘detached, observing and thoughtful’ one, improves the outcome of real and placebo treatments. Similarly, studies have shown that providing a definite (positive) diagnosis and ‘overselling’ the effectiveness of the proposed treatment also improves outcomes.

THE DECLINE EFFECT

The positive effect of enthusiasm on outcome is thought to explain the so-called ‘decline effect’, whereby initially strong results of new treatments tend to fade in later studies.

When I was a student and a young doctor, every year or so a new type of anti-inflammatory drug (a nonsteroidal anti-inflammatory drug, or NSAID) was released. There are many such drugs and they are very commonly prescribed. There was always one preferred drug that was perceived to be the best, in that it was thought to be the most effective and to have the fewest side effects (usually gastrointestinal irritation). This preferred drug was seen to be better, and all other NSAIDs were thought to be pretty much the same as each other.

But when a new NSAID was released, it replaced the previously preferred drug, which became just as good as all the others – it wasn’t as good as we first thought it to be.

This went on, drug after drug, until the ‘COX-2 inhibitor’ NSAIDs were released. These drugs became the preferred NSAID, as (yet again) they were thought to be more effective and have fewer gastrointestinal side effects than previous NSAIDs. Those two points have been argued, but what did become clear is that Vioxx, one of these new drugs, really was different to the previous drugs in that it was more likely to result in cardiac side effects and death, and that drug alone has been estimated to be responsible for tens of thousands of deaths in the US alone.

While initially positive findings that are later found to be less positive or even negative has been referred to as the decline effect, it is not really a declining effect. Often, the effect was never there and the positive findings were due to bias in the conduct and reporting of the studies, not to mention selective publication and marketing.

This ties in with the lack of reproducibility in scientific research covered in the last chapter. A good example of this effect was given in an editorial on vertebroplasty (a procedure covered in the next chapter) titled ‘The vertebroplasty affair: the mysterious case of the disappearing effect size’. It’s a good example because it shows how the effectiveness (effect size) appeared to decrease with better and better studies – from observational studies, to non-randomised comparative studies, to non-blinded randomised studies, and eventually to placebo-controlled blinded randomised studies, at which point the effectiveness essentially disappeared.

What happened was not that the effect disappeared, but that our estimate of the true effect was moved closer to the true effect by using better scientific methods; the perceived effectiveness resulting from bias within the poorer studies was gradually removed.

And this is the reason for the ‘decline effect’ in many cases: the initial studies were biased due to a lack of scientific rigour, and due to the prevailing biases and enthusiasm of the researchers, publishers, marketers, the media and the public. The later studies merely used better (scientific) methods to uncover the true effect.

Breast cancer: bone marrow to the rescue

Chemotherapy can provide marginal survival benefits in patients with solid tumours, such as breast cancer. The same goes for radiotherapy. However, the dosage of chemotherapy or radiotherapy is limited by its toxicity, particularly to the bone marrow.

For patients with severe breast cancer, it was thought that better survival would result from very high doses of chemotherapy/radiotherapy, knocking out the bone marrow (doing this would normally kill you), and then injecting previously harvested bone marrow cells in order to regenerate the bone marrow (a bone marrow ‘rescue’ or bone marrow self-transplant).

It was complex, expensive and risky – all of which served to raise expectations.

This heroic treatment was tried, and it was reported that patients did well. Really well. The practice consequently spread in the 1990s, but (as usual) without any scientific experiments (randomised trials) to demonstrate its true effectiveness.

Pressure from doctors, patients and other interest groups grew, demanding funding for this complex and expensive procedure. In one case, a health insurance company settled for US$89 million after being sued for not providing the treatment, even though the patient died soon after receiving the treatment (using money raised by donations). Soon after, the health insurers fell into line, and covered the procedure. After this, the practice spread further, with further reports of good results (one study stating that it was ‘8 times better than conventional treatment’).

What happened next was a bit odd. One randomised study was reported in 1995 showing excellent results with bone marrow rescue, and this supported the observational evidence to date. Interestingly, however, a later inspection could not determine whether the control patients in this study ever existed.

What finally happened (after the practice was established) was that some doctors decided to perform a proper randomised trial to scientifically test the treatment. They had difficulty recruiting for the studies, because people assumed that the treatment worked. They were also criticised as being unethical, because of the assumption that the control group would be denied an effective treatment – highlighting the problems with trying to test treatments after they have become common practice.

Eventually, four randomised studies were completed and these were presented around 1999. The studies showed that the treatment didn’t work. Due to the great cost and risk involved with this procedure, it was quickly stopped and this treatment is not done any more.

THE INCREASED PLACEBO EFFECT OF INVASIVE PROCEDURES

Pills can only go so far in their ability to generate a placebo response. More ‘invasive’ placebos work better than pills. In studies of placebo injections compared to placebo pills, the injections win hands down. In fact, procedures are the way to go when we want to create the best placebo.

In a blinded comparative study of placebo acupuncture (needles) and a placebo pill, the needle worked better, but only for pain and subjective symptoms. There was no difference in more objective outcome measurements such as grip strength. This reinforces the fact that placebos work best for subjective symptoms (pain, headaches, depression, even nausea and dizziness), which, if they work at least partly by psychological means, makes sense.

In a review of the placebo effect in osteoarthritis, similar findings were noted in that the more active the intervention was (like using an injection or acupuncture instead of tablets), the stronger the placebo effect on pain, and the more blinded the patients were, the more effective the placebo.

THE THERAPEUTIC ENVELOPE

There is one more important ingredient to the placebo effect: like a good salad, the secret is in the dressing. In other words, it is not just the placebo itself that needs to be constructed to provide the maximum effect; it is also the environment in which it is given. This is called the therapeutic environment or ‘therapeutic envelope’. It helps the patient believe that they are getting active treatment and reinforces the expectation that the treatment will work. Symbols of science, hospitals, white coats, an authoritative figure, and an enthusiastic care provider all help the placebo effect. This aspect covers everything from the waiting room environment and the degrees hanging on the wall, to the community perception of the treatment. And regarding the room in which the therapy is provided, there can be no ‘theatre’ more capable of providing the expectation of benefit and the perception of applied science and technology than an operating theatre.

° ° °

So, to summarise, in order to get the greatest placebo effect possible, you need to give the most elaborate, painful, costly, invasive and time-consuming placebo possible, give it in an environment filled with authority figures and technology, all administered by an enthusiastic supporter of the treatment. I think it is safe to say that surgery ticks all these boxes on the placebo list. Combine these factors with societal expectations (which are high for surgery), our desire to see things work, and some ‘scientific’ support (usually from observational, potentially biased studies) and you have then built up enough placebo effect to cure cancer. Well, at least that’s what they thought in the 1990s (see above, ‘Breast cancer: bone marrow to the rescue’).

So if surgery fits the theoretical model of the perfect placebo, where is the hard evidence that it has a placebo effect? Fortunately, there are cases where this has been investigated; studies where patients have been assigned to either real surgery or sham surgery, and results compared between the two groups. This is the subject of the next chapter.

4

PUTTING SURGERY TO THE (PLACEBO) TEST

EXAMPLES OF STUDIES USING SHAM SURGERY

IT IS ESTIMATED that in 2006 there were seventy-five randomised trials published in the medical literature every day, and there are now over 20 million medical articles published, yet there have only ever been a handful of published placebo (sham) studies involving surgery. There are ethical and practical objections to performing placebo surgical trials. The practical ones are valid, but are by no means insurmountable. The ethical reasons have been debated at length and are summarised here. Largely, they stem from the fact that a sham procedure involves exposing patients to at least some degree of harm (like an incision or a sedative or anaesthetic) for a procedure that does nothing to directly benefit them.

Giving someone an ineffective (placebo) treatment goes against the medical ethos, particularly if we believe that there is an alternative, effective treatment. It makes no medical sense to expose someone to potential harm, or to deny them known effective treatment. However, if there is any doubt about the effectiveness of the treatment, and you really want to know if it works, using a placebo makes perfect scientific sense.

Scientifically, if you are going to do an experiment to test a hypothesis, you should do it the best way possible. The scientific view can take into account the bigger picture (beyond the individual patient) by considering the downside of continuing to provide a possibly ineffective treatment (possibly harming people unnecessarily), and the need to make sure that everybody gets the right treatment into the future. The potential benefit to society is weighed up against the risk to the individual participants in the trial. Also, those volunteering to participate in the trial get to weigh up these risks and benefits themselves before signing on.

In short, science takes a global, societal perspective in which the risk to the individual is balanced against the potential good to society. The practice of medicine tends to concentrate on the individual, avoiding harm or risk wherever possible.

As you can see, there is conflict between the ethics of research and the ethics of the clinical practice of medicine. Scientific research is concerned with providing a reliable, precise, unbiased estimate of the truth, and will accept some imbalance between benefit and harm at an individual level in order to provide that estimate, because the results can be used to provide a better guide for future patients. As long as those harms are minimised, and the patients are properly informed and agree to participate, the study will be deemed ethical by the approving ethics committee. Medical practice, on the other hand, cannot ethically support the administration of potentially harmful or knowingly ineffective treatment to a patient when an alternative exists.

The problem, however, is that medical practitioners don’t know with any great certainty that any treatment is effective unless we subject it to scientific tests.

Medicine has been getting around this imbalance by assuming effectiveness in the absence of rigorous scientific tests. Once practices become commonplace, it becomes ‘unethical’ to test them scientifically for fear of denying patients the (seemingly) effective treatment. We end up where we are today, with a plethora of treatments, some of which are effective, some of which are not, and no certainty regarding which is which.

When discussing the ethics of placebo surgical trials, it is worth considering the fact that so many of the placebo surgical trials that have been performed have shown surgery to be ineffective, and also that history is dotted with common surgical procedures that were later shown (without placebo studies) to be ineffective and harmful – harm that could have been avoided with an initial placebo surgical trial. Importantly, all of these treatments were considered to be effective when they were in common use.

When people claim that a proposed placebo trial is unethical because they ‘know’ that the treatment is effective, the evidence supporting that claim needs to be examined closely. It is often deficient.

Now let’s look at those placebo surgical trials. The common thread in these studies is that many patients improve after the real operation, just like in real life – it’s not as if nobody gets better. The catch is that a similar proportion of patients improve after the sham operation, indicating that the real operation is no more effective than the sham surgery. This shows that when we see patients get better after we treat them, it is not necessarily due to the specific effect of our treatment. We (the doctors and the patients) perceive effectiveness by attributing a cause and effect relationship to the association we see.

In a recently published systematic review of all placebo trials of surgery it was found that in about half of the fifty-three trials found, surgery was not better than placebo treatment. And in the ones where it was better, the difference wasn’t great.

This may not be big news to some, but this review was important because it highlighted many of the problems with surgery, namely that:

1   placebo studies are needed to determine the true effectiveness of surgical procedures, but …

2   surgery and its associated devices are regulated less strictly than drugs, consequently …

3   surgery is often not subjected to placebo/sham studies, even though …

4   such studies are ethical and practical.

The review was performed partly because of the lack of appreciation and understanding of the placebo and non-specific effects associated with surgical procedures. The publication of the review will increase that understanding and go some way to making such studies culturally and ethically acceptable. And by showing that such trials can be (and have been) done, it is more likely that researchers will consider using placebos in future studies.

It’s disappointing that the studies included mainly tested minor procedures; over half involved either inserting balloons (to stop bleeding) or using endoscopes. Many of the other, more significant procedures are covered in this chapter.

The response to the study – or rather the lack of it – was also disappointing. Nobody cared much, and practice certainly didn’t change. In fact, one of the (very few) responses provided in the British Medical Journal was from Russia, from a reader who lamented that so many outdated, ineffective and harmful surgical procedures (like radical mastectomy, major surgery for stomach ulcers, and lung denervation for asthma) were still being performed routinely in parts of the former Soviet Union.

What follows are examples of studies comparing surgery to sham surgery. They have been chosen for the breadth of surgery covered, for their importance in changing surgical practice, and for specific illustrative points that they carry.

SURGERY FOR ANGINA, ’50S STYLE

The first placebo surgical study dates from 1959, and relates to a surgical procedure for angina (chest pain from lack of blood supply to the heart) that dated from 20 years earlier: internal mammary artery ligation.

The procedure involves blocking (ligating, or ‘tying off ’) an artery that runs inside the chest, near the heart, in order to divert more blood to the heart. The operation had everything going for it: biological plausibility (meaning it made sense, at least on superficial consideration), support from animal experiments, and good results from a series of patients who had the procedure. Already, you have about as much evidence as is behind many of the surgical procedures performed today, and enough evidence to claim that a randomised trial is not necessary or is unethical. And this procedure was not considered experimental; it was performed in many institutions across the US.

The 1959 sham surgery experiment involved surgery on all of the participants, but half of them didn’t have the artery ligated, and the patients were ‘blinded’ to the type of treatment they received (real or sham). Most patients in both groups felt better (in fact, all patients in the study improved their exercise tolerance after the procedure). The catch was, of course, that they were no more likely to improve if they had the real surgery than if they had the sham surgery, showing that the treatment did not have a specific therapeutic effect, only a perceived effect. Basically, the operation didn’t work. The study was small (only seventeen patients enrolled), which might make you think that it was not a powerful enough study to detect the advantage of surgery, but I can counter that with the observation that the patients in the placebo group actually did better than the (real) surgical group for most outcomes. I agree that a larger study may have been more conclusive about a difference between the groups: it might have been able to show us that the surgery was significantly harmful.

The good news is that the operation fell out of favour after publication of the sham study, unlike some of the examples that follow.

SURGERY FOR PARKINSON’S DISEASE

In Parkinson’s disease, there is a lack of dopamine in parts of the brain. This chemical can be replaced in pill form, but with variable effect, and with some side effects. In the 1990s many clinics were transplanting dopamine-producing cells from embryos into the brains of people with Parkinson’s disease. This procedure involved drilling holes in the skull, through which the cells were inserted. Animal studies showed that the cells could survive, and that the procedure could correct some of the movement disorders. Open-label trials (unblinded, without placebo) of these transplants in humans showed that patients improved. Again, there was as much evidence as there is for most surgical procedures performed today: a biologically plausible mechanism, supportive lab studies, and reports of patients getting better after the treatment.

If you search the internet for the trials done on this procedure, you will find more articles written about the ethics of these trials than actual trials published. There were high-profile articles from the authors of one of the trials defending their use of sham surgery, and equally high-profile articles questioning the ethics.

There were two trials done, one in 2001 and one in 2003. In the 2001 trial, published in the New England Journal of Medicine, twenty patients were randomised to each group (fetal cells or sham surgery). The results for the primary outcome (the Global Rating Scale) were very similar between the two groups, with basically no improvement in either group. This is interesting, because it is usual in studies of this type that both groups improve, but by a similar amount.

Interestingly, the authors concluded that ‘Human embryonic dopamine-neuron transplants … result in some clinical benefit in younger but not in older patients.’ They were able to conclude this by performing multiple subgroup analyses for various outcomes until they found one combination for which the patients undergoing real surgery did a little better. In this case, they found that for certain outcomes, in younger patients, when tested in the morning (prior to their medication), the transplant group did better than the sham group. A subgroup analysis like that should not trump the primary outcome on which the study (and the hypothesis) is based. It is like getting every student in a classroom to toss a coin ten times, finding the kid who flipped eight or nine heads out of ten (individually unusual, but likely, given a big enough class) and concluding that heads are more likely to appear than tails in coins tossed by kids like that.

It should also be noted that major adverse events occurred in 42 per cent of the transplant group, compared to 5 per cent in the sham group.

The quality of life outcomes for the same patients (reported in a separate study) showed no significant difference between the surgery and the sham groups, and in that study both groups did improve. Interestingly, patients who thought they got the active treatment did significantly better than those who thought they got the sham, regardless of what they actually received (their guesses were no better than chance, which shows that the study was well blinded). If just thinking they got the treatment made them better, how much improvement would there be if patients knew they got the treatment, as when we report the results of surgery? That might explain why the early observational studies were so favourable, and it casts a shadow over most studies of surgery, which do not use placebo controls, or any controls for that matter, let alone blinding.

The 2003 trial of thirty-one patients in three groups had a few minor differences (general anaesthetic instead of local, and the addition of immunosuppression), but they basically tested the same thing, right down to the sham surgery. The active group did a little better than the sham group, but the difference was not statistically significant. Inevitably, the researchers found a subgroup where the transplant fared better than the sham (ironically, it was the mild cases), but at least they had the scientific integrity to correctly conclude that ‘Fetal nigral transplantation currently cannot be recommended as a therapy for Parkinson’s disease based on these results.’

A side note on subgroup analyses. If a study shows no overall difference in the outcomes between the two treatment groups in your study, it is quite likely that if you break down your patients into various subgroups based on age, gender, disease severity or even star sign, you will find a group that did better with your treatment. But because the overall effect was the same in both groups, it means that for every subgroup that did better, there has to be another subgroup that did worse with your treatment, otherwise the overall average difference would not be zero.

This kind of surgery for Parkinson’s disease is like a lot of surgical treatment: it sounds good superficially, but when you think about it for a while, it doesn’t. To me, putting dopamine-producing cells into the brains of people with Parkinson’s makes as much sense as injecting bone cells into people with osteoporosis. To think that we can correct the vast complexities involved in a disease that we do not fully understand by injecting some cells from an embryo is, at best, a little naïve.

SURGERY FOR MENIERE’S DISEASE

Meniere’s disease is a disorder of balance (dizziness) and hearing (ringing or hearing loss). The underlying cause is not known, the symptoms often fluctuate, there is crossover with other symptoms (vertigo, migraine), and there are many other conditions that cause ‘Meniere’slike’ symptoms. This makes the condition ripe for any treatment to look good if we think it works, due to the subjective nature of the symptoms, symptom reporting that is open to misinterpretation, the fluctuating nature of the condition, and the lack of any objective pathological test. Therefore, for such conditions, reporting good results from a series of patients is not enough; a more scientific (unbiased) assessment is necessary. Fortunately, somebody did just that. Unfortunately, despite the results of that study, surgery (now in many different forms) is still being used for this condition.

Most operations for this condition aim to equalise or lower the pressure in the inner ear or middle ear, despite any good evidence that ‘pressure’ is the problem in the first place. The landmark Danish study of thirty patients from the 1980s reported no difference in outcome in a surgical group versus a sham surgery group, but interestingly about 70 per cent of patients significantly improved in both groups. And everything got better, even the nausea and vomiting.

The authors got the idea of using a placebo because they had previously used lithium (a drug) to treat the disorder (based on some biologically plausible mechanism that they made up) and noticed sustained improvement in 70 per cent of patients. Later placebo studies showed that lithium and placebo both gave sustained improvement in 70 per cent of patients. In fact, the authors noted that all treatments then available for Meniere’s disease (medical and surgical) had good results in 60–80 per cent of patients. (Note that 60–80 per cent is a very common rate of improvement for many studies of treatments that are later shown to be no better than placebo, and for many treatments that have not been rigorously tested).

The results of the surgical sham study three years and nine years later (provided in later reports) were unchanged: there was still good improvement in both groups, with similar rates of improvement in the active and the placebo groups. The high rate of improvement is likely to explain the fact that surgery (in one form or another) is still commonly performed for Meniere’s disease. None of the newer operations have been tested in a similar way, and despite the results of this previous sham trial, surgery will continue to be offered as long as patients seek it, surgeons are allowed to do it, insurance companies pay for it, and, of course, as long as we still believe that it works.

The other study (from 1988 and also from Denmark) compared the same (active) operation to an alternative operation (not a placebo). Largely, there was no difference, except a few people in the alternative group lost their hearing. They would have been better off with a placebo.

SURGERY FOR MIGRAINE

Migraine is common, affecting millions of people worldwide. A patent foramen ovale (PFO – a ‘hole in the heart’ that lets blood cross from the right side of the heart to the left) is also common, present in about 30 per cent of people.

An association between migraine and PFO has been shown in some studies, in that people with a PFO are more likely to have migraines. And when cardiologists started performing procedures to close the PFO (for other reasons), they noticed that patients often reported that their migraines were better. When faced with facts like that, our brains are quick to kick in, jumping straight to the conclusion that the association represents causation. Consequently, doctors started developing theories about how (not ‘if ’) migraines could be caused by a PFO. Maybe something from the right side of the heart (the venous circulation) is getting through the PFO and going to the brain (arterial circulation)? Migraine is associated with brain changes on MRI that might be caused by emboli (particles in the blood that can block blood vessels) getting through the PFO – could that be the proof? Or maybe it is some chemical that is leaking across the PFO?

But migraine is episodic, not constant like blood flow through a PFO. And migraines are usually well localised to one part of the head, whereas emboli are scattered throughout the brain. And PFO leakage gets worse with age, whereas migraine decreases with age. And many people with migraine do not have PFO, and vice versa. To me, this means that the people developing these causal theories hadn’t thought it through.

But that didn’t stop people from treating migraine by inserting devices in the heart to close the PFO holes. And in ‘observational’ studies, they saw just what they expected to see: the migraines got better. Was this a case of ‘believing is seeing’?

Later, a blinded placebo (sham) trial was done comparing PFO closure (using a device inserted through the groin) to sham closure (just an incision over the groin). The results showed that patients who had their PFO closed had fairly good improvements in their migraine measures, just as in the previous observational studies. Unfortunately, the improvement seen was not much better than that seen in the sham group.

The authors tried to make the procedure appear effective by doing a secondary analysis that excluded patients in the PFO closure group that did very badly (had lots of migraines). Once these patients were excluded, they noticed that the PFO closure group did a little better than the sham group. Yes, that’s right: if you remove the really bad patients from one treatment group, and then recalculate the scores on the remaining patients, that treatment suddenly looks a lot better. I wish I could do that with my surgical results: maybe next time I present my surgical results, I’ll first remove the patients that fared poorly.

An accompanying editorial noted something interesting. When the results of the sham study were initially presented to a major cardiology conference (prior to publication) they were positive, showing a significant reduction in one particular outcome (the number of days with migraine) in the group that had their PFO closed (although the primary outcome and the overall cure rate were still not better). So why did the published study show no significant difference? Maybe the researchers got excited when they stumbled on some positive results and only later realised that they had forgotten something (like including the patients with bad results)?

The real test of a trial is the primary endpoint – the outcome that all the bets ride on. The researchers expected 40 per cent of the PFO closure group to have no more migraines, compared to 15 per cent in the sham group. They based these expectations on the results seen in the observational studies. In the end, only 4 per cent had no migraines in the follow-up period – exactly the same in both groups. It’s a great example of how surgery appears less effective the more scientifically you look at it.

And, as usual, things didn’t go perfectly – just as in life. Some patients never had much of a hole to start with, and some hearts still leaked after the closure was performed; but even allowing for that, the procedure still didn’t make any difference to the migraines.

I think the theory of a causal connection is still alive – those types of theories are hard to kill because they’re what we all want to hear. Hopefully, not many people are having this procedure done for their migraines. Not just because it probably doesn’t work and is expensive, but because the placebo study also showed a higher than expected rate of complications in the group that had the device inserted to close the PFO. Things like getting the device stuck in wrong part of the heart, having it float off into the lungs, cardiac tamponade (bleeding in the sac around the heart), and pericardial effusion – complications that the authors referred to as ‘transient’.

KNEE ARTHROSCOPY FOR ARTHRITIS

An arthroscopy (keyhole surgery) on the knee joint is one of the most common procedures in orthopaedics, and one of the most common surgical procedures overall, with over one million performed in the US each year.

In 2002, researchers from the US published the results of a placebo-controlled (sham surgery) study of arthroscopy in patients with knee pain and osteoarthritis. They were middle-aged and older patients, mostly with mechanical symptoms. One hundred and eighty study participants were randomised to one of three treatment groups: an arthroscopy with removal of loose bodies, torn cartilage and menisci; an arthroscopy and wash-out only; and a placebo only (just the incisions). All patients had similar scars, and they were blinded to which treatment they received. Even the researchers doing the follow-up didn’t know what treatment group the participants were in, eliminating any bias when assessing the outcome.

Over two years, there was no difference between the groups, in knee pain or function. As usual, most patients in all groups got better; they just got better by the same amount. Actually, the active group did a little worse, but the difference was not great.

Understandably, the study was criticised by surgeons who felt that the results did not fit with their experience. It has been supported by other (non-sham) randomised trials since, and there is some evidence that the rates of knee arthroscopy for osteoarthritis fell slightly after this study was published, but there are still many being performed, and the rates in many countries are increasing. Why? Probably a combination of failure to accept the evidence, patient and referrer expectations, financial incentives, the desire to do something when nothing else is effective, and also because it ‘works’. It just doesn’t work any better than a placebo.

KNEE ARTHROSCOPY FOR A TORN MENISCUS

One of the criticisms of the papers that tested arthroscopy for osteoarthritis of the knee was that the treatment wasn’t directed at those specifically with a meniscus tear: the most common reason for arthroscopic surgery. In 2013, a placebo-controlled trial was published comparing surgical excision (via arthroscopy) to sham surgery for patients with signs and symptoms of a medial meniscus tear, with a proven meniscus tear on MRI, and without any significant arthritis in the knee.

This study was high quality. Not only did the researchers follow the usual steps in reducing bias by not letting anyone know in advance which group they would be in and keeping nearly all the patients right to the end of the study, they also made sure that not only were the patients and researchers blinded, the statisticians were blinded. They even went to the extreme of writing the paper before revealing (to themselves) which group was the sham. They also checked that the blinding was successful (it was) by asking patients whether they thought they got the sham treatment.

The results showed that there was no statistically significant or clinically important difference between the real surgery and the sham surgery for any of the primary outcomes (like knee scores, knee pain after exercise, and general health) at any of the time points. And, of course, most patients showed considerable improvement after the treatment – it just didn’t matter whether or not the torn meniscus was removed.

Even in very rigorous studies, however, we can only extrapolate to patients in similar circumstances. The study did not look at lateral meniscus tears, only medial (there are two menisci in the knee), and did not include patients with acute traumatic tears or locked knees, so we cannot generalise to that group. Most patients who undergo knee arthroscopy, however, are those with knee pain consistent with a tear and with an MRI scan showing a tear – exactly the type of patient picked for this study.

It should be noted, though, that most people over forty have a meniscus tear, nearly everyone with osteoarthritis has a meniscus tear, and of all the people in the community that have a meniscus tear, most do not have knee pain. The link between the presence of a meniscus tear and knee pain is not strong, and the link between taking it out and relieving pain is even more tenuous, but we continue to do this procedure in record numbers. You have to admit, we surgeons are a dogged bunch.

NOT SUCH A GREAT IDET

IDET (intradiscal electrothermal therapy) is the perfect example for this book: it has biological plausibility, hightech equipment, high cost, conflicts of interest, great lab results, encouraging results from early clinical studies, and no advantage over placebo.

The idea behind IDET is to reduce back pain by inserting a probe into the painful disc (the whole idea of the disc causing pain in the first place is another story …), and then heating it up to ‘shrink’ the disc, or ‘seal’ the disc, or kill the nerve endings, or whatever. Trust me, you don’t have to kill that many animals to be able to show that stuff like this does something in lab experiments.

The inventors of IDET wrote some reports about how patients got better with this treatment. Interestingly, about 70 per cent of them got better. Seventy per cent is looking like the magic number for placebo treatments, so when I see reports of any series of patients that show that around 70 per cent improved, I am immediately suspicious, and then I start looking for the real evidence: blinded randomised trials.

But the inventors knew that reports of case series weren’t going to be enough, so they wrote a review article. This article summarised their previous reports, thereby appearing to build up the evidence base. It used unscientific terms that raise my suspicion of ineffectiveness, things like ‘very promising’, and ‘an attractive alternative’. Apparently, that was all that the FDA needed to approve it. That approval, along with the appeal of a new, high-tech treatment with some kind of biological plausibility, and some positive publications (regardless of how weak), is all it takes for new treatments to flourish.

Then some researchers did a blinded placebo study where the patients and the people doing the evaluations didn’t know who got the active treatment and who got the placebo (sham IDET). The results of the first study? Absolutely no difference between the two groups, of course.

Interestingly, there was another placebo study published a year earlier which showed important pain improvements in more patients in the active group than in the sham group (56 per cent versus 38 per cent). When studies disagree, it can be hard to work out where the truth lies, but the initially favourable results have failed the basic test of replicability. And that raises suspicion.

Is it too much to ask for these studies to be required before devices are approved and released?

Yet IDET is still being used widely. Many more case series (without any comparison or control group, let alone a placebo) have been published showing that patients still get better after this treatment, about 70 per cent of the time. But this kind of evidence is no better than the evidence for a lot of other things that don’t work, because the supporters fail to realise that back pain will improve in about 70 per cent of people after almost any treatment, as long as it is given in a supportive and credible way, like any good placebo.

You’re probably thinking that if this thing works in 70 per cent of patients, what’s my problem? Firstly, I don’t want to pay for it (whether in taxes, health insurance premiums, workers’ compensation premiums, or in the opportunity cost for doctors and patients due to the resources wasted on this ineffective treatment), and secondly, because it can be harmful, as demonstrated by reports of massive disc rupture, dead vertebral bone and loss of nerve function as a result of IDET. I expand on my objections to using the placebo effect in Chapter 8.

And the punchline? The guys who developed the technology with a start-up company in 1995 (and wrote the supportive articles) sold their company three years later for $300 million. This makes the conflict of interest statement in one of their papers – ‘One or more of the author(s) has/have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript’ – one of the great understatements of all time.

TENNIS ELBOW SURGERY, ANYONE?

For decades, surgeons have been reporting good results with surgery for tennis elbow (lateral epicondylitis). In a classic article from 1961, the late, great British surgeon RS Garden reported that the results of surgery for tennis elbow were such that ‘no patient failed to benefit in some way from the operation’. Fifty years later, in a review of eighty patients undergoing surgery for tennis elbow, seventy-eight were reported to have improved. There are plenty of non-surgical treatments out there for tennis elbow, all of them reported as having good results, yet none of them, when tested, are any better than placebo. Why then, did it take so long for a randomised trial to be done comparing real surgery with sham surgery?

The study, of course, showed no advantage to real surgery over sham surgery. And, of course, patients in both groups got better. There was, however, one difference in outcome between the sham and real surgical patients; the surgical patients had more pain at two weeks.

Patients improve after any treatment for tennis elbow, just not because of the treatment. Take steroid injections, ultrasound (shock wave) therapy, orthotics and acupuncture – they are all perceived to ‘work’ (in that patients usually feel better at some time afterwards), but they all fail when put up against a well-blinded placebo.

The article by Garden from 1961 is worth a read, if only to see the standard of surgical research at that time. It is actually a comprehensive case series, but it contains many logical and methodological flaws that are largely hidden to the reader (and probably the author). Most telling is Garden’s attitude: ‘no patient failed to benefit in some way from the operation’. It was clear to him that the operation was successful, and in a sense he was right; it’s just that the patients didn’t get better because of the surgery, and his study did not prove that they did.

Garden also said that surgery was usually not necessary because the results of steroid injections were so good. Yet at best, steroid injections only give short-term relief. I reckon that if you didn’t mix the steroids with local anaesthetic, you wouldn’t even get the short-term relief. In fact, a recent study showed that all of the common treatments (and there are a lot of them) for tennis elbow are not much better than placebo on observation alone, over the intermediate to long term.

Many operations currently being performed for subjective complaints (usually pain) have not been tested against placebo and are performed for the very reason that Garden performed surgery on tennis elbow: because the patients seem to get better afterwards.

VERTEBROPLASTY

Vertebroplasty is a procedure involving injecting bone cement (an acrylic) into the vertebral body to ease the pain of a crush fracture – usually the result of osteoporosis. The fracture causes acute pain that normally resolves, so if anything needs a placebo trial, it is vertebroplasty.

In Chapter 3, I described the ‘decline effect’, where the initial enthusiastic results from the proponents is not reproduced in later studies, as the scientific validity of the studies improves over time. Studies with better scientific methods will, by definition, have less bias (causes of error) and therefore the results will provide a better estimation of the truth. Vertebroplasty (injecting osteoporotic vertebral fractures with cement) is a case in point.

The decline in effectiveness of this procedure was documented in an editorial in The Spine Journal. Initial reports of vertebroplasty, without controls (comparison patients), were very positive. Some comparative studies were also positive (but less so). There was still some apparent benefit when some non-placebo randomised clinical trials (RCTs) were done. But by the time the two blinded placebo-controlled RCTs were done, the effect was gone.

The RCTs were scrutinised in a published report by the North American Spine Society – and so they should be, as there is no such thing as a perfect study. That is what science is all about: putting your findings out there for scrutiny. The authors addressed the criticisms, and even went to the extent of publishing a systematic review in the British Medical Journal, combining their data in order to answer the criticism about not having enough acute (fresh) fractures. It is a disappointing fact that many doctors are dismissive of these RCTs, but are less critical of the unblinded, uncontrolled or non-placebo controlled studies that confirm their beliefs.

To quote the lead author of one of the sham trials: ‘Vertebroplasty appears to confer no benefit over placebo but poses some risk … The onus is on the proponents of the procedure to perform further high-quality randomized placebo-controlled trials.’

This is also my answer to critics of such studies: if you don’t like this one, then show me the sham study that proves that the treatment is effective. Why, if you don’t like the study, would you assume that the opposite is true?

And what about the risks? These are mainly due to the potential for leakage of the cement around the nerves or into blood vessels, causing nerve damage or an embolism. Not bad for a placebo.

SURGERY FOR HIGH BLOOD PRESSURE

One of the most recent casualties of the sham surgery trial is a procedure called renal denervation (cutting the nerves to the kidney). Years of good results reported in scientific publications were contradicted by a blinded sham-controlled trial that showed no significant benefit over placebo.

Renal denervation is a procedure that involves damaging the nerves to the kidney (an organ that has some role in controlling blood pressure). It is usually done in patients with high blood pressure who do not respond to medications. It is approved for use in many countries and thousands have been (and probably still are) performed worldwide.

Previous reports (without blinded control groups) showed that the blood pressure falls after this treatment, dramatically. It should be noted that the blood pressure (on average) also fell quite a bit (14 mm Hg) in those receiving renal denervation in this sham study. The point is that the blood pressure also fell in the sham group (12 mm Hg), either from natural history, other treatments or behaviours, regression to the mean, or what we have decided to loosely refer to as the placebo effect. The fact that both groups improved by a similar degree (there was no significant difference) means that the surgery had no specific effect (of its own).

This study differs from the previous examples because it measured something objective (blood pressure), not pain or patient-reported improvement. It is known that the placebo effect mainly works for subjective outcomes (like pain and headache). The fact that this study showed that a surgical procedure provided improvements in an objectively measured outcome, and that the improvement was similar to that seen in the sham group, means that we need to rethink the effectiveness of so many other procedures that we are currently performing (and not testing). It reinforces the model of the properly controlled, blinded, placebo study as the best way to find out what really works, not just what we think works. It is the scientific method that allows us to tease out causation from the tangled knot of associations that we see.

THE PATIENT’S PERSPECTIVE:

‘WELL IF I HAVE TO HAVE IT,

THEN WE SHOULD GO AHEAD’

Often phrased as a question, this comment always provokes this response from me: ‘Nobody has to have surgery.’ Surgery is rarely life saving, even for cancer, and in my field of orthopaedics it almost never is. And when I hear this comment, the patient is usually referring to a hip replacement or some other elective procedure. The definition of elective surgery is that the patient ‘elects’ to undergo the procedure; that is, they don’t have to have it. I usually explain to patients that rather than surgery being necessary, it is an option, and, like all their options, there are risks and benefits that need to be weighed up.

The comment stems from the faith that many people have in a doctor’s decision. I understand that the doctor has the qualifications and experience in the relevant field, but that doesn’t mean that they must make the decisions. Doctors should advise, and then let the patient make the decision. That advice, however, should be objective and not biased in favour of surgery. Unfortunately, many surgeons ‘see’ surgery to be more effective than it really is, and patients will tend to follow their lead.

So you can see some common threads from these examples. For fluctuating, vague, subjective complaints, a lot of treatments are associated with improvement in the majority of patients, but when compared to placebo, there is no difference. The patients improved (or thought they did) because of the reasons described in Chapter 1.

The other common thread in these examples is that these treatments were all in common practice before the placebo study was done, and several remain in common practice despite the results of the studies. This is because the drivers of surgical treatment are not restricted to the clinical studies. These drivers include tradition, biological plausibility, related studies (like lab studies), and financial incentives.

But most of all, I believe that surgery is driven by successful ‘results’. When surgeons feel that patients improve after their treatment, when causation is assumed in the face of only association, it becomes a belief that is pretty hard to shake, even if you were inclined to try. After all, assuming cause and effect is how we are wired; it is often the quickest and easiest explanation; and it often coincides with what we were expecting and what we wish to be true.

5

THE SURGICAL SCRAP HEAP

OPERATIONS THAT HAVE FADED AWAY DUE TO A LACK OF EFFECTIVENESS

THIS CHAPTER CONTAINS only a selection of the procedures that have been discarded over the years; there are many others. These procedures were not tested against a placebo, but were shown to be ineffective or unnecessary in other ways. I have chosen the examples in this chapter because of their relevance to surgery, and because of the lessons we can learn from them. I have also tried to stick to treatments that were commonplace in their time, which indicates that they were perceived to be effective, at least by the surgeons who recommended them.

BLOODLETTING

Bloodletting would be the first, but it has already been covered in the introduction to this book. Bloodletting is an important example because it contributed to the rise of the surgeon practitioner, and was probably the longest-running placebo treatment in history. Because its use was so widespread, it probably killed more people than any other medical treatment in history. To learn more, see ‘Bloodletting, the 3000-year-old placebo’ on page 7.

RADICAL MASTECTOMY

When I did my surgical training I assisted in many mastectomies, including radical mastectomies. The hundred years of surgery leading up to that time involved a race for the most radical operation for breast cancer. The theory made sense: cancer invaded your body starting from the breast, so the more you excised – the ‘wider’ and more radical the excision – the less likely it was that there would be any cancer left behind to spread.

The theory was wrong, but the lack of any comparative trials meant that the theory was accepted based on its simplicity, the fact that it represented common practice, and the lack of any evidence to prove otherwise.

A randomised trial comparing lumpectomy (removing just the tumour) combined with local radiotherapy to a more radical mastectomy showed that the results of the two treatments were similar, even though at that time there were questions about the effectiveness of radiotherapy.

More questions have since been raised – questions about whether breast cancer is a localised disease, amenable to local control, or a ‘systemic’ disease. And questions about the effectiveness of local excision influencing the course of the disease outside the breast.

For a complete mastectomy, the long-term survival rate is the same as for having a lumpectomy, with or without radiotherapy. When excising breast cancer, you are no less likely to have a local recurrence if your margin of excision is 5 millimetres compared to 1 millimetre. Furthermore, if you leave some tumour behind (an incomplete excision), it does not alter your long-term survival. And, like surgery, more radiotherapy is not necessarily better: extra radiation (a higher dose) may change the local recurrence rate, but it doesn’t improve the survival rate.

All of these results fly in the face of the seemingly logical theory behind radical or total mastectomy, but the results of clinical research trump any theory, and consequently radical mastectomy is no longer routine treatment for breast cancer. Although there is evidence that local treatment (surgery and radiotherapy) can influence the rate of local recurrence, it has little or no bearing on overall survival.

Recently, a large-scale, long-term follow-up study on the lowest grade of cancer, ductal carcinoma in situ (DCIS), showed that the chance of dying from breast cancer up to twenty years after treatment is just as good with lumpectomy alone, and that there is no advantage to a full mastectomy or radiotherapy. Again, local recurrence was higher with lumpectomy alone, but the overall chance of dying from breast cancer was the same.

How many women could have been spared the physical and psychological harms of radical mastectomies over many decades if proper trials had been done earlier? This is another reason why I disagree with those who claim that such surgical trials are ‘unethical’. I believe it is unethical to perform new treatments without such proof of effectiveness.

Please note that I am talking about mastectomy to treat cancer, not to prevent it – prophylactic mastectomy is a whole different question and the evidence around this is still being developed.

LOBOTOMY

In the 1940s and ’50s (tapering into the ’70s and ’80s) tens of thousands of prefrontal lobotomies were performed in Europe and North America for many types of mental conditions. It was done because doctors at that time believed that it worked, and they didn’t have many effective alternatives. However, it didn’t work: it made people worse and it even killed a few, despite a Nobel prize being awarded to one of the developers of the procedure.

Prefrontal lobotomy is a medical procedure that disconnects the frontal lobes of the brain from the rest of the brain (think Jack Nicholson in the final scene of One Flew Over the Cuckoo’s Nest). The role of the frontal lobe is complicated; it is involved in many higher brain functions.

A 1942 article titled ‘Prefrontal lobotomy: the surgical relief of mental pain’ (love that title!) was an influential paper written by two major proponents of lobotomy and it started a wave of lobotomies across the US. The paper is full of biased statements stemming from the authors’ belief that the procedure works, which colours their interpretation of the results that they witnessed. This aspect makes interesting reading (see the quotes below). The authors don’t deny that the procedure changes patient personality, but they believe that the patient’s ‘overall personality’ (whatever that means) improves. So what happens after a lobotomy? According to the authors, ‘after incision … the patient becomes unresponsive, disoriented, confused and is freed completely from his anxieties.’

Of course, it was all thought to be scientific. The operation was based on observations in animal studies and from patients with brain injuries and tumours. Yes, animal studies … for human psychiatric conditions. This quote is from one of the animal researchers who started it all, observing the effect of a lobotomy on a chimpanzee: ‘If the animal made a mistake, it showed no evidence of emotional disturbance … It was as if the animal had joined a “happiness cult …” and had placed its burdens on the Lord!’

Outstanding scientific reporting, not. The early reports supporting lobotomy were bad science. There were no comparisons provided, let alone a controlled trial. There were no objective independent tests and no patient-reported outcomes, beyond those filtered through the treating doctors, who fitted what they observed into their belief that the procedure worked. One claim was that many patients became easier to manage – calmer. That part, at least, may be true. But as one critic put it: ‘[although] it makes the custodial care of many patients easier, [let] me remark in passing that killing them makes their custodial care still easier’.

The performance of lobotomy simply to make patients easier to manage probably did take place, as lobotomy was performed on patients in mental institutions and people with behaviours and conditions considered undesirable, like schizophrenia, neurosis, depression and chronic back pain, as well as children with behavioural disorders and homosexuals.

However, the decision-makers at the time were probably just acting on their (erroneous) beliefs, rather than through any malice. This is an important point, because the harm done by practices like this is often attributed to ill intent, and this is unusual in my experience; it may be due to ignorance, poor science, perverse incentives, herd mentality, laziness and other aspects of human nature, but not usually a desire to harm.

But in this case, the lack of desire to harm was not enough to prevent the harm from occurring. Many (including many famous people) died from lobotomies (from arteries being severed in the process). Even if they survived, the personality changes were often severe. A lobotomy removed higher function and made the patients placid. They might have lost their anxieties and behavioural issues (or at least their ability to express them), but they lost a lot of what made them human in the process: their frontal lobes.

In order to avoid having to use a general anaesthetic, or an operating theatre, and drilling holes in the head, one of the proponents developed a technique where an ice pick was passed into the brain through the eye socket and – well, here’s a good description:

a patient would be rendered unconscious by electroshock. Freeman would then take a sharp ice pick-like instrument, insert it above the patient’s eyeball through the orbit of the eye, into the frontal lobes of the brain, moving the instrument back and forth. Then he would do the same thing on the other side of the face.

One of the pioneers of lobotomy was a Portuguese neurologist named António Egas Moniz, who developed the procedure for humans in the 1930s. He was awarded a Nobel Prize for this work in 1949 – coincidentally the same year he was shot in the spine and paralysed by one of his patients.

Lobotomy was a common procedure that was based on a biologically plausible mechanism (which was rubbish) and was thought to be effective, based on biased and unreliable observational evidence. In reality, it killed some people and in those who survived, their behaviour and personality were changed, unrelated to their initial complaint – they just complained less.

EXTRACRANIAL TO INTRACRANIAL BYPASS SURGERY

Strokes are due to a blockage in the blood supply to the brain. They can be transient or permanent, mild or severe, and can be fatal. The idea of diverting blood from an artery outside the brain (extracranial) to bring extra blood to a blocked artery inside the brain (intracranial), like most treatments in this section, seemed logical. It was considered a no-brainer, and that is how it worked out – although literally rather than figuratively.

The idea is appealing: if an intracranial (inside the skull) artery to the brain is clogged and causing strokes, then bringing in blood from a good blood vessel (extracranial – outside the skull) to the brain artery to bypass the narrowing will prevent future problems. Extracranial to intracranial (ECIC) bypass was first done in the 1960s and became an established procedure based on the observation of success, not on any randomised trials comparing the procedure to non-operative treatment.

The randomised controlled trial (RCT) published in 1985 showed that surgery did a little worse than non-operative treatment. The trial started in 1977 and was of a surprisingly high standard, particularly for that time. For example, it used concealed randomisation, a predetermined calculation of the number of participants required, clinically important outcomes, a large number of participants (for a surgical study), 100 per cent follow-up, only about 2 per cent crossover (meaning that the patients generally got the treatment they were supposed to get), and long-term follow up (average five years). And importantly, the surgical procedure worked, technically – the surgical complication rate was low and they had a 96 per cent graft patency rate, so the poor results were not due to a failure to achieve the goal of bypass surgery.

The results, however, showed that fatal and nonfatal strokes occurred more frequently and earlier in the surgical group. The results were enough to reject the hypothesis that surgery improved the outcomes.

The authors couldn’t resist the temptation to play around with the analyses, adding and subtracting ineligible patients, looking at severe strokes only, type of strokes, strokes per person, size of the treating hospital, the artery involved, etc. In every analysis, there was no benefit to surgery. They even did an analysis excluding patients who had strokes prior to surgery (a best-case scenario, biased to make surgery look good), and there was still no benefit.

So how do we explain the previous ‘successes’? Simply, the previous studies were biased. They used surrogate endpoints, like cerebral blood flow, cerebral metabolism and EEG (electroencephalogram) tracings; the RCT used clinically important endpoints (stroke and death). The previous studies did not have an adequate (concurrent, randomised) control group – they used ‘historical’ controls (from other studies). They also relied on variations in the natural history, using outcomes like transient ischaemic attacks (TIAs) instead of strokes. For example, one previous (uncontrolled) study showed an 86 per cent benefit from surgery. The RCT showed a similar high rate of reduction in TIAs of 77 per cent, but the reduction was 80 per cent in the non-operative group – which highlights the need for a control group.

Basically, the randomised trial was a more objective, less biased test and therefore more likely to provide an estimate of the effect that was closer to the true effect. The previous studies were more likely to show a positive effect, even when there wasn’t one. This is partly because it was what the researchers wanted to and expected to find, and this influenced their choice of methods and their interpretation of the data.

The ECIC bypass story is a great example of how much bias is out there in medical studies; bias that leads us to overestimate the effectiveness of the treatment. But it is also a good example of how a more rigorous application of scientific principles leads us to a better estimate of the truth, and consequently to better treatment.

PLICA SYNDROME

Keyhole surgery has been a boon for surgeons. By lowering the risk associated with the procedure, we can justify so much more. And when we first looked into the knee joint all those years ago, we started doing what humans do: we linked whatever it was we saw to the patients’ symptoms. Then we started doing what surgeons do: we devised operations to start treating our made-up conditions. Plica syndrome is an example of one of those conditions.

The existence of plicae (the plural of plica, meaning a fold in the lining of the joint) was known for some time, but the ‘syndrome’ really took off from about 1980. That’s when surgeons started doing arthroscopies. Every knee they looked into was sore, and they could see the plicae, which looked a little funny, and weren’t usually included in the anatomy textbooks, so they simply put two and two together, and as usual got five, and a new diagnosis was born: the plica syndrome.

As with so many conditions, if a patient has a complaint, and the doctor can see something that looks funny on any image taken near the sore part (an arthroscopy, an MRI, whatever), they go into basic human mode and assume cause and effect between the two, in this case without even establishing an association, let alone a causal one.

Luckily, or conveniently, plica syndrome was about the easiest condition in the world to treat: you just cut it. Patients appeared to get better, and that is about as much proof as we ever need. When I was training junior doctors, I saw plicae get cut all day.

Some surgeons reckoned they could tell who had plica syndrome by examining them. They then did an arthroscopy and found that they were right about 90 per cent of the time, and published the findings. This is not a good way to test the diagnostic accuracy of your physical exam. Firstly, the initial diagnosis could have influenced their decision to label someone with plica syndrome during arthroscopy. Secondly, how many people have a plica in their knee anyway? According to one study, it is around 90 per cent. A random number generator could guess the diagnosis just as effectively. Another study tested the accuracy of examination. Unsurprisingly, they were also right about 90 per cent of the time. That’s about as clever as holding a coin up to your forehead (in order to use your mind to read the probabilities contained within the coin) and then predicting that it will land on heads 50 per cent of the time.

Another study looked at pre-operative MRI scans of patients treated arthroscopically and couldn’t relate any of the findings on the scan to whether or not the surgeon took out a plica.

The ‘success’ of surgical treatment for plica syndrome varies from about 50 per cent to 100 per cent, like the success rate for just about any treatment for just about any condition. But without ever validating the diagnosis or doing any comparative trials of treatment, we have no idea of whether this is a real condition or not, let alone whether the treatment really does anything. But there is no incentive to do such a trial, as long as the public keeps trusting surgeons to ‘diagnose’ it, and pays them to treat it; and as long as some of them say they feel better afterwards, there is no need to rock the boat.

° ° °

The common themes of placebo surgery have again been shown in this chapter: commonplace operations, assumed to be effective based on a plausible theory and the observation that some people got better after these procedures. No other scientific endeavour, from manufacturing widgets to putting humans on the moon, would tolerate such sloppy practice. But in surgery it is no big deal to do a harmful procedure without good scientific evidence that the patient is any better off than if you had not done the procedure, simply because nobody has compared the two alternatives head to head, often on the basis that it is ‘unethical’.

The objection that studies comparing surgery to non-operative treatment or sham surgery are unethical could not be further from the truth; what is unethical is operating on someone without good evidence, as in the examples listed above. This is not to say that current surgical procedures without such evidence are not effective. Some procedures are likely to be effective and some are likely to be ineffective, but in the cases where highquality comparative studies have not been performed, we simply don’t have a reliable way of knowing the difference.

6

TODAY’S PLACEBO SURGERIES

CURRENT SURGICAL PROCEDURES UNDER QUESTION

MANY OPERATIONS performed today do not have the support of high-quality evidence that compares them to placebo surgery or to non-operative treatments. For example, our research unit reviewed all orthopaedic surgical procedures performed in three large public hospitals in our local area and found that of about 9000 procedures performed, only about half of the operations performed had been compared to non-operative treatment in randomised trials. That figure was not very surprising and is not at all unusual for surgery, but what did surprise us was that of the procedures being performed that had been subjected to comparative studies, about half of the studies showed that the procedure was not better than the non-operative alternative.

The first problem, that only half of the procedures had been tested in a randomised trial, is called an evidence gap – missing evidence due to untested procedures. For those procedures, we lack reliable evidence. The second problem, where procedures that were shown to be ineffective are still being done, is called an evidence – practice gap: we have the evidence, it just hasn’t been translated into practice. Both of these gaps are large.

For many surgical procedures performed today, there is either a lack of good-quality evidence regarding effectiveness, or the evidence that does exist is conflicting. When this happens, we find that the likelihood of the procedure being performed is based on availability, and on the perceptions of the surgeon and the patient regarding the likely effectiveness.

If there is no good evidence available for a certain procedure, or if the evidence is conflicting, I cannot say with any confidence that the procedure is not effective. Similarly, the proponents should not be able to conclude that the procedure is effective. However, they do, based on their perception: they see people get better and conclude that their improvement is a result of the procedure. I have covered the problems with making such a conclusion before: for example, the patient may have improved anyway, there might be a placebo effect, and we might not be seeing the patients who do not improve (who go elsewhere).

We can get some clues about which procedures do not have good supporting evidence, because when the decision to operate is dependent on surgeon preference, there will be practice variation – that is, there will be differences in the numbers of procedures being performed in different regions and by different surgeons.

Practice variation may be a legitimate reflection of different patients or of different degrees of access to services between populations, but when practice variation persists after allowing for possible legitimate reasons, we have what is termed unwarranted clinical variation. This has been studied fairly extensively and various health maps have been produced to show the variation. As expected, the variation is highest for procedures that do not have clear evidence behind them.

When studying unwarranted clinical variation, the procedures that often show up as having the greatest unwarranted variation between geographic regions are spine fusion and hysterectomy. These are good places to start on our search for possible placebo operations amongst procedures performed today.

Please note, I am not saying that each of these procedures is a placebo, or is ineffective, because often we don’t have good evidence either way. Sometimes there is evidence that is unfavourable towards the procedure, but either way, these are the procedures that are probably being overdone in some way. The term ‘inappropriate’ care, or unnecessary care, is likely to be applicable to these procedures in many cases – meaning that the procedure is unlikely to consistently provide a benefit that outweighs the risks involved.

BACK FUSION SURGERY

Spine fusion (getting two neighbouring vertebral bodies to heal together) can be done for many reasons, but the most common reason is degenerative conditions (wear and tear, arthritis, spondylosis) in the lumbar spine. Yet there is very little evidence that spine fusion surgery for back pain is effective. It is very expensive (the implants alone are often tens of thousands of dollars per case), often leads to complications, often requires further surgery, is associated with increased mortality, and often does not even result in the spine being fused. That last one is not a big deal, because the results of the surgery are not well correlated with whether or not the spine fuses. Nor are the results related to how you fuse the spine (from the front, the back or sideways), or whether or not you use implants (screws, rods and cages), except that ‘instrumented’ fusions (using implants, which is now routine) are associated with more complications than old fashioned ‘uninstrumented’ fusions.

The rate of spine fusion surgery is increasing and has been increasing for many years. The rate in the US has gone way past the rate of one spine fusion per 1000 population per year. It has overtaken hip replacement surgery and continues to rise. The rates of surgery vary widely across the US, where back fusion is associated with a high degree of practice variation. In my state, New South Wales, back fusion just beats prostatectomy as the procedure with the most regional variation. The US rates are far higher than in most other countries, but the rates in many of those other countries are increasing too.

Several reasonably decent randomised clinical trials have been published comparing surgery to non-operative treatment for back pain. There have been no sham surgery trials, but the evidence from these trials indicate that this surgery might achieve its results through the placebo effect.

Two of the studies put spine fusion surgery up against structured non-operative treatment alternatives: cognitive behavioural therapy in one study, and intensive physical rehabilitation in another. These studies found no significant differences in the outcomes between the operative and non-operative groups (except that the complication rate in the surgical group was higher). As usual, both groups showed improvement. The point is that roughly the same proportion of patients in each group improved, by roughly the same amount.

A third study concluded that the surgical group did better. Interestingly, the surgical group didn’t do any better than in the other studies; the difference was that the non-operative group didn’t get better at all. This is because the non-operative treatment was not dressed up as something that might work (that is, it wasn’t a good placebo). The authors state that the non-operative treatment ‘could vary within broad but commonly used limits reflecting the nonsurgical treatment policy in the society’. Patients were basically given more of the treatment that they had received before – the treatment that had previously failed and that led them into the study. Faced with more of the treatment that had already failed, this group was unlikely to get better, because it is unlikely that they expected to get better.

If back fusion is as good as exercise, how good is exercise? Interestingly, in the rare cases that physical therapies have been compared to sham treatments, there is no consistent difference in the results between real and sham exercise.

One could reasonably conclude that if you do something (anything) that looks like it might work for back pain, is structured and has plausibility, about two thirds of the patients will get better, as for many of the placebo treatments already discussed. With spine injections many patients improve afterwards, but when compared to placebo injections in properly blinded studies, the results are no better.

Surgery for back pain has the exact effect I would expect it to have if it was a placebo. If it was a placebo, it would also explain why it doesn’t matter what surgical approach you use, whether or not you put any implants in, and whether or not the spine fuses.

I once attended a course by an internationally renowned spine surgeon (yes, I used to be a spine surgeon, and I used to do spine fusions) who explained that nearly all treatments for back pain result in improvements in about two thirds of the patients. I asked him why he did spine fusions for back pain, if it was no more effective than the alternatives. He said, ‘Because it works in about two thirds of the patients.’

The other thing about spine fusion surgery is that even the case series aren’t that great. Re-operation rates of 20 per cent or more after only a few years are common, persistent pain is common, and ongoing need for treatment such as physical therapy and opioids is common. The failure of spine surgery is so common that it has been given a name: failed back syndrome (FBS). One study showed that the most common cause of death after spine fusion surgery is opioid overdose.

Spine surgery is not just a sugar pill; it is a much more elaborate placebo than that, and it is much more dangerous. The onus is on doctors to prove that spine fusion surgery for back pain is better than placebo before subjecting so many people to the risks of such major surgery. Millions of people have had spine fusions for back pain and I am not at all convinced that the benefits of this surgery outweigh the considerable harms. Also, with a back-of-the-envelope calculation multiplying 500 000 spine fusions per year in the US (including neck fusions) at an average cost of $100 000 each, I am certainly not convinced that it is worth $50 billion per year. Somebody is winning here, and it isn’t the patients.

SURGERY FOR MS

Multiple sclerosis (MS) is a debilitating, progressive degenerative neurological condition that varies greatly between patients, in severity and in the types of symptoms and signs. For such a condition, it can be difficult to measure changes or improvements; people may feel better and describe improvements that are not easily measured objectively. Also, the condition fluctuates over time. All of these factors mean that any treatments need to be tested in an objective way, and preferably with the patients blinded.

The story of surgery for MS has the common themes of many other procedures in this chapter, and it may be considered the most representative of what is wrong with surgery, and of why I wrote this book. It has a pioneering surgeon championing the treatment, a theory out of left field that is attractive on superficial examination, positive results from case series, individual and patient advocate support, laboratory evidence, widespread uptake prior to any controlled trials, lots of money changing hands, and finally a single, small comparative study, which showed no benefit and possible harm from the procedure. And to top it all off, the operation continues to be used.

An Italian vascular surgeon suggested that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI), which is a narrowing in the veins that drain blood from the brain to the heart. He developed this theory after identifying CCSVI in patients with MS. The theory goes that increased pressure in the veins (from the narrowing) leads to blood cells leaking through the blood–brain barrier, which leads to iron deposits in the brain, which leads to something else, which leads to MS. The biological theory is of little importance to me, because the correlation between any biological plausible mechanism and whether a treatment works or not is loose, at best. The proof of the pudding is in the eating.

A study from 2009 reported the outcomes of an open label case series that showed good improvement in MS in cases of relapsing remitting (RR) MS and secondary progressive (SP) MS, but not in primary progressive (PP) MS. He reported improvements in the clinical condition and the MRI findings.

Other studies, including a larger case series of over 250 patients from 2012, also showed that most patients improved after treatment of CCSVI, again with less improvement in the PP type.

The fact that good results were seen in the fluctuating form of the disease (RR) is a sign that the results may be – how shall I put it? – open to interpretation. Few would deny that for this treatment, given the claims of success, the uncertain mechanism and the mismatch between this theory and previous theories of the disease, a blinded randomised trial was called for. As Carl Sagan said, ‘Extraordinary claims require extraordinary evidence.’

But before doing the randomised trials, some researchers attempted to establish whether CCSVI is even ‘a thing’. What is normal venous pressure? What are the criteria for a diagnosis? Is CCSVI really more common in MS? One study published in The Lancet in 2014 showed that if you used the gold standard (injecting dye in the veins), you were more likely to see CCSVI than just doing an ultrasound, but the presence of CCSVI was not more common in MS patients than in their unaffected siblings or in other unaffected individuals. An earlier, larger study of nearly 2000 people from 2013 found that CCSVI was no more common in MS compared to other neurodegenerative disorders or unaffected individuals.

The author of the Lancet paper is doing a randomised controlled trial in Canada that is still to report. To his credit, the surgeon who developed the theory and the treatment is also doing a large randomised trial comparing the treatment to sham. An earlier attempt at such a trial had difficulty recruiting patients (a problem for sham surgery trials), but they published their results of nineteen patients (ten with real treatment and nine with sham) in 2014. They found that the clinical results were not better with the treatment. In fact, they were a little worse, and the MRI scans showed more lesions in the active group. They concluded that the treatment is not effective and may exacerbate the underlying disease.

Given the evidence so far, and my scepticism and knowledge of how easily the current evidence can be influenced by bias, I predict that the Canadian study comparing CCSVI treatment to sham will not show a significant benefit from the procedure. I am basing this prediction on the unconvincing evidence of effectiveness so far, and on the likelihood that CCSVI is not even associated with MS in the first place.

In the meantime, hopeful and desperate people with a debilitating disease are travelling around the world and paying thousands of dollars to have this procedure performed. Many feel better afterwards, but objective evidence of improvement in their underlying condition, and any evidence of long-term benefit, is lacking.

HYSTERECTOMY

Hysterectomy is the removal of the uterus, a common procedure, with hundreds of thousands performed each year in the US. There are several indications (reasons) for the surgery; commonly it is done for gynaecological problems like endometriosis, excessive bleeding, uterine prolapse and fibroids, although the contribution of these conditions to pain varies and sometimes it is done simply for pelvic pain when other treatments have failed. It is also performed to remove (ovarian) cancer, but this is much less common.

Because hysterectomy is (usually) an elective procedure and not a life-saving procedure, it is probably understandable that there is some variation in the rates of surgery between regions. It is expected that there will be some variation in doctor and patient preferences, for this condition. But this is not a minor procedure, and a threeto fourfold variation in the rates between and within countries, adjusting for gender and age, is a little worrying. So are studies that show it is more commonly done by male gynaecologists than female, and that it is more often done within certain social classes. And although it is more commonly performed in richer countries, there is still considerable variation, with rates in the US being high and those in Norway being low (less than a quarter of the US rate).

There has been considerable debate about the necessity of hysterectomy for these benign conditions, but unlike some other procedures that are rising, the rate of hysterectomy is falling, particularly for those common, benign indications. One study noted that from a peak in 2002 to 2010, the rate of hysterectomy for the conditions listed above fell by over 40 per cent.

I can’t say why the rate has fallen, or whether it came from the doctors, the payers or the patients. The improvement in alternative (non-operative) treatments probably played a part, but I think that this might also be a case where the surgeons were changing practice to fit the evidence. Given the persistent variation, however, there is still a way to go.

But hysterectomy is only part of the problem. Most pre-menopausal women who have a hysterectomy also have their ovaries removed, in case they are causing problems or might in the future (like ovarian cancer). Unfortunately, there are unintended consequences of removing a woman’s ovaries — things like heart disease, stroke, Parkinson’s disease, dementia and fractures (from osteoporosis). There is also some evidence that removing the ovaries, while decreasing your chance of dying from ovarian cancer (an uncommon cause of death), increases your overall chance of dying (probably from much more common conditions like cardiovascular disease). Although there is debate about whether removing the ovaries increases the chance of these complications, particularly if hormone replacement is used, I am not sure I would want to have this done if I were a woman. Yet hundreds of thousands are done each year, without good evidence of a benefit.

CAESAREAN SECTION

More common than hysterectomy is the caesarean section (C-section), which often beats hysterectomy for regional practice variation. The variation in C-section rates during childbirth is well documented, between hospitals, states and countries. There is also variation based on socioeconomic status and financial incentive. The rates also vary over time, but here the pattern is at least consistent: unlike hysterectomy, the rate is increasing. So what? Sure, there are complications, but isn’t that worth it if we are saving lives? As usual, it turns out that we have been overestimating the benefits and underestimating the harms of C-sections, which may explain the overuse of this treatment.

In 1985, the World Health Organisation said that countries with the best neonatal mortality rates had C-section rates of about 10 per cent and suggested that the C-section rate should not be more than 10–15 per cent. That was challenged by the obstetricians and has since been withdrawn. The rate in developed countries is now around 30 per cent (higher in the US and Australia) and around 50 per cent in China and Brazil. Rates have roughly doubled in the last twenty years. The US rate in 1970 was 5 per cent.

Let’s first look at how the benefits are overestimated. The reasons given by obstetricians for the increasing C-section rates are as follows.

Increasing obesity in mothers

Obesity is associated with increased complications during childbirth, and C-sections are more likely to be done if the woman is obese. But C-sections in obese women are also associated with higher complication rates, such as infection. Obesity on its own should not be a reason for a C-section.

Increasing maternal age

C-section rates increase with increasing maternal age, but often because the woman chooses the procedure, rather than because it is necessary.

Breech presentation

Again, vaginal breech births are associated with increased complications, but that doesn’t mean that the current situation of performing a C-section on women with breech presentation is necessary. Firstly, the improved outcomes from breech presentation that have been recorded are not necessarily due to increased C-section rates. Secondly, C-section can often be avoided by manually repositioning the baby before labour. One study from 2002 in women with breech presentation compared C-section to a trial of labour. It showed better outcomes for the baby with C-section, but guidelines published since, based on further evidence, have concluded that a trial of labour is reasonable and safe. The use of C-section as the default has meant that midwives and doctors have become deskilled and have lost confidence regarding handling vaginal breech deliveries.

Induction

Induction is associated with increased C-section rates but, again, we need to ask the question: why are the induction rates so high? Induction may be overdone for many reasons, as the benefits only apply when the birth is well overdue (after 41 weeks), not at 38 and 39 weeks, and certainly not to make it convenient or in some way easier for the women or the doctors. In fact, one half to two thirds of inductions are done for non-recognised conditions.

Fetal heart rate monitoring

CTG (cardiotocography, or electronic fetal monitoring) is one of those things that sounds like a no-brainer: why wouldn’t you monitor the baby’s heartbeat during labour? Fortunately, we have the answer to that question: because it does not lead to an improvement in survival of the fetus in uncomplicated cases. It does, however, increase the rate of medical intervention (such as C-section and instrumented birth – forceps, etc.). This is yet another reason for the high C-section rates that doesn’t stack up.

Failure to progress

The failure of labour to adequately progress is not a very objective measure. Several studies have shown that the diagnosis of ‘failure to progress’ is increasing, and is responsible for some of the increase in C-section rates.

Previous C-section

This is the main reason for having a C-section. Talk about making business for yourself! If you do a C-section on first-timers, you will be doing one on everyone. It is uncommon and challenging to have a vaginal birth after a C-section, due to the fear of uterine rupture. This is partly driven by defensive medicine and partly left over from when C-sections were done with a vertical incision (increasing the likelihood of later rupture). Now, the risk of uterine rupture with a trial vaginal birth after a prior C-section is one in 500, and of those, the risk of perinatal death is less than one in 1000. That’s roughly a one in 500 000 risk of death with a trial of normal birth. Despite recommendations from government bodies suggesting a trial of (normal) vaginal birth, and good evidence that this is likely to be successful and safe, the rate of C-section following previous C-section is proving hard to budge.

Now we will turn our attention to the underestimated harms.

Immediate harms

The direct, early harms are well documented and are much less than they were a hundred years ago (maternal mortality is now as low as two in 100 000). It’s not perfect, but it’s pretty safe. It’s still an operation, so it is prone to well-known but rare complications and the occasional complication out of left field. Complications that may occur include excessive bleeding, anaesthetic complications, wound infection, endometritis (inflammation of the lining of the uterus), urinary tract infection, damage to surrounding structures (for example, causing urinary incontinence), blood clots, hysterectomy and wound breakdown.

Later harms

This is what everybody misses. After mum and baby have gone home and no longer need to see the doctor, problems can and do occur. Firstly, the scarring that results from the C-section can lead to serious complications in over 2 per cent of later pregnancies due to uterine rupture, placenta previa (low-lying placenta) and placenta accreta (where the placenta grows into the uterine scar and doesn’t peel away after the baby is born, causing bleeding and often requiring surgery). These scarring issues make each subsequent C-section surgery more difficult, more prolonged and more prone to complications.

Secondly, many complications to the baby have been reported, including problems from abnormal intestinal bacteria, depressed immune function, obesity, respiratory compromise, poor maternal–infant bonding and breastfeeding issues.

Thirdly, there are other complications such as persistent pain at the site of surgery, endometriosis (where endometrial tissue that normally lines the uterus grows outside the uterus, elsewhere in the pelvis), adenomyosis (where endometrial tissue grows in surrounding muscles), bowel adhesions and obstructions, abnormal periods and numbness around the scar.

Fourthly, there is a cost involved. C-sections are more expensive than normal births. That money could be spent on, say, providing more midwives in order to prevent more C-sections.

What can be done?

1   Not using an obstetrician for an uncomplicated birth. Obstetricians are more likely to get women started on the cascade of interventions (monitoring, scanning, inducing, etc.) that culminate in C-section. A study from Australia showed that the caesarean section rate (and the epidural rate, and the episiotomy rate, and the use of neonatal intensive care) can be reduced in low-risk women by using a midwife instead of an obstetrician.

2   Change the culture in the maternity unit by providing training on vaginal breech birthing techniques; provide increased midwife support (one to one); and provide a multidisciplinary review of C-section cases to see what can be learned and if future cases can be avoided.

3   Change the culture of the community by providing information to the public about the relative risks of management options for pregnant women, and providing data on clinical outcomes for each maternity unit.

A Cochrane review of interventions to reduce the unnecessary C-section rate, such as getting a second opinion, providing women with more information, reviewing practice and trialling labour, shows that the C-section rate can be significantly reduced.

In my opinion, the overuse of C-section highlights problems that are representative of much of modern medicine. There is a distorted perception of risk that leads to a tendency towards more interventions, and leads us to go for the knife when there is doubt. This is reinforced by the knowledge that you are less likely to get sued for doing a C-section than for recommending a normal birth.

KNEE ARTHROSCOPY

Although covered in the previous chapter, this falls within the list of procedures still currently being performed, commonly. In the last chapter, I covered the sham surgery evidence, which showed no benefit for arthroscopy in arthritic knees, and no benefit in removing a torn meniscus in knees without arthritis. In this section I will look at whether we are at a tipping point for knee arthroscopy.

A colleague from Finland published an article about knee arthroscopy, stating that due to the weight of evidence against arthroscopy, it was now time to ‘abandon ship’. There are other surgeons who have been saying the same thing, and I think it makes a difference to surgeons when another surgeon tells them something. Surgeons are used to being criticised by non-surgeons, so they tend not to pay too much attention to them. Somehow, there is greater acceptance (among surgeons) of your message if you are a surgeon – you have street cred.

There are many surgeons who have spent years performing arthroscopy (and seeing patients improve) who have difficulty in letting go of their beliefs and tend to look for ways around the evidence when faced with it. But I also know many surgeons who, faced with similar patients, feel that arthroscopic surgery is not helpful. Interestingly, these surgeons often come to the conclusion that arthroscopy is ineffective through their own observation, not through the evidence from sham studies. One of these groups of surgeons must be wrong.

I think that arthroscopy might be going the way of hysterectomy: it won’t disappear, but the rates will drastically fall. There have been several reports noting that the rate of arthroscopy has not fallen since the first sham study from 2002. But there are other studies showing that it has plateaued, and, given the rising population, particularly of older patients with degenerative knees, this means that the rate per person is probably falling.

Some local data has led me to think that the tipping point may have come. I recently gathered statistics from my state (population about 7.5 million) to look at the arthroscopy rates in the different health regions. I wanted to see if the rate in my local health area had declined since 2011, when we started to change our practice in some hospitals. I was pleased to see that the rates of knee arthroscopy in patients aged over fifty in my health district have fallen since 2011 – by about 50 per cent in three years. I was surprised, however, to see that they were also falling in most of the other health districts, with a 15 per cent fall across the state over the same period.

They say that it takes about ten years for evidence to make it into practice. Of course, that will vary depending on so many factors, but in this case that prediction may prove correct.

For knee arthroscopy, the bottom line is that if you have pain and degenerative changes in your knee (like mild arthritis or an undisplaced meniscus tear), then regardless of the kind of symptoms you have (‘mechanical’ or not), regardless of what your X-rays look like, regardless of where the arthritis is, regardless of how bad your pain is, and regardless of whether or not the MRI scans show your meniscus to be torn, and of whether or not you have an MRI at all, having an arthroscopy will not increase your chances of getting better, compared to a sham surgery. Nor will it arrest or reverse the degenerative changes in your knee. Believe me, I would love for arthroscopy to work (it is a great operation and pays well) but for arthritis and degenerative tears in the meniscus (which is most patients with knee pain) it doesn’t.

THE PATIENT’S PERSPECTIVE:

‘WHATEVER YOU SAY, DOC’

This is a variation on the common attitude of ‘But the surgeon said I needed it.’ They both signify complete trust in the doctor’s decision. This is lazy on the part of the patient, and this attitude makes the doctor’s decision making equally lazy; if no one is going to question them, then it doesn’t matter what they do.

An extreme but common example of this is the patient who gets better on the waiting list – a common occurrence for patients waiting for knee arthroscopy. When I started practice, I did knee arthroscopies for sore knees, because that is what I was taught, and it seemed to kind of work. Often, I would see patients just before their operation, after they’d been on the waiting list for a few months, and when I asked them how their knee was feeling they’d say, ‘Pretty good – no real problems.’ ‘Then why are you here?’ I would say (maybe a little more indirectly) and the answer was very telling: ‘Because you said I needed it’ or ‘I thought I’d get it done anyway, just in case.’ The belief in surgery is so powerful that people believe it is needed even when there is nothing wrong with them.

APPENDICITIS

There is one particular thing (out of a list of many) that makes me disappointed in a surgical trainee; it comes after they describe a new case to me and offer their preferred surgical treatment. I ask them for the evidence supporting their recommendation. They sometimes say, ‘Well, I saw a guy do one once.’ This short statement says so much. Firstly, it shows how much we are influenced by what we see, particularly when somebody considered to be senior or authoritative does it. It also shows how readily we recommend treatments without good knowledge of the outcomes of that treatment, or of the alternatives. It is easier just to think, ‘If this guy did it, then it must be OK.’

This is one reason why so many procedures like appendicectomy are so commonly done. Randomised trials have told us that removing the appendix is not necessary on first presentation, and is associated with a worse long-term outcome. Yet if you present to any of my hospitals with suspected appendicitis, you are unlikely to be leaving hospital with your appendix.

A review published in the British Medical Journalsummarised the randomised trials that compared immediate appendicectomy to antibiotics and observation for patients presenting with uncomplicated appendicitis (not a ‘burst’ appendix, for example). They concluded that the overall complication rate was significantly lower in the group initially treated non-operatively. It seems that we may have been overestimating the benefits of having an appendix removed straight away, and we might also have been underestimating the harms from the surgery (such as infections and adhesive bowel obstructions). What a surprise.

The fact that many patients in these studies later had an appendicectomy does not alter the results of initially treating them non-operatively. The bottom line is that most appendicectomies can be avoided, resulting in an overall reduction in the complication rate.

On questioning surgical colleagues, I come up against unscientific, emotive responses like ‘What if it was your child?’ The answer, of course, is that I would want them to have antibiotics and observation rather than an immediate appendicectomy.

As an aside, I have never understood that line of reasoning. When I recommend non-operative treatment, I am often asked what I would do if it was me, or my mother, or whatever. I usually remind them that my recommendation is based on the best available evidence, that non-operative treatment has a greater probability of a good result, and that the degree of separation between the patient and me, personally, does not change that.

For things like appendicectomy, it often boils down to comments like ‘But this is what we do here’ from the surgeons. That is the attitude that kept venesection (bloodletting) going for a few thousand years, and for another hundred years after it was shown to be ineffective. It is time for tradition to take a back seat to scientific evidence. Shouldn’t we at least be informing the patients of the possibility of non-operative treatment, and getting their input?

CORONARY STENTING

The idea behind ‘revascularising’ coronary arteries is very appealing: ‘My blood vessels were blocked and the doctor unblocked them.’ Like so many things addressed in this book, this sounds good and seems hard to argue with, unless you look at it scientifically and ask the right questions.

The debate between the cardiothoracic surgeons (on the side of coronary artery bypass grafts or CAGs, in which blood vessels from elsewhere, like leg veins, are used to bypass obstructed arteries in the heart) and the interventional cardiologists (on the side of angioplasty/ stenting, in which tubes are placed inside the blocked heart arteries to open them back up) continues. There are dozens of clinical studies comparing these two treatments for heart disease. Everybody wants to know which one is best, but I am more interested in whether either of them is better than not doing them.

The best evidence tells us that there is no difference between these two methods when it comes to the chance of dying, and not much difference for anything else, except that you are more likely to need another ‘revascularisation’ with stenting. That would only be important, however, if revascularisation was important in the first place. The fact that the stents block up a lot more than the CAGs didn’t seem to affect the comparison that much. Even the newer, more expensive drug-eluting stents (which contain drugs to reduce later blockages) don’t confer any advantage over the old ones when it comes to keeping you alive or preventing a future heart attack, and yet they are much less likely to block up within the first year. If the blockage is the problem in the first place, why doesn’t it matter if your revascularisation blocks up or not?

As a pragmatist, if I had a blocked artery I would like to know if revascularising my blocked blood vessels actually changes my chance of dying. I could spend some time explaining how my heart has compensated for the blocked vessel, as witnessed by my continued existence, or I could ask why the high blockage rates in these stents don’t actually seem to confer any disadvantage, but that is just stacking biological explanations up against opposing explanations, a theoretical game that can go on forever. The arguments about what treatment is best and how it works distract us from asking the most important question: ‘Am I less likely to die if I have this procedure, compared to if I don’t?’

So what is the evidence? For ‘stable’ heart disease (not an acute heart attack), the largest and best known study comparing stenting to not doing a stent showed no advantage to stenting in any of the outcomes measured: mortality, heart attack or hospitalisation. And the most recent review of this topic came to the same conclusion.

Even for ‘acute coronary syndrome’ (like a heart attack), a review of the randomised trials shows that there is no significant advantage in overall survival over five years for patients having routine invasive angiography/ stenting.

There are differences in many other things, but not the big one – the chance of dying.

Recently, the American College of Cardiology put stenting on its list of the top five tests and procedures whose necessity should be questioned. So even they agree that you should question your doctor if he or she wants you to have your arteries unblocked – it is not as simple as it sounds.

Why does the procedure persist? One study detailed why cardiologists choose to stent patients, even when they know there is no clinical benefit. The reasons were: just in case, medicolegal, theoretical benefit, to relieve anxiety, avoid regrets, etc. This shows up the desire to intervene when we are in doubt, a topic covered in Chapter 7.

VENOUS CLOT FILTERS

It seems I will never run out of examples of treatments that sound obviously effective in theory, fall into common use based on the strength of a proposed biological mechanism, but fail to show a significant benefit when put to the test. The story of the IVC filter is another one of these.

Deep venous thrombosis (DVTs, clots) in the leg can dislodge, travelling up through the main vein in the pelvis and abdomen (inferior vena cava, IVC), through the heart and then embolise in the lungs as a pulmonary embolus (PE), sometimes causing rapid death. An IVC filter is a cage placed in the IVC that snares clots that have broken free from the leg veins, trapping them before they can travel to the lungs. The device has been used for decades, but without much evidence of benefit, as two recent reviews have revealed.

The main randomised trial that was performed on IVC filters did show a reduction in the rate of PEs (extending over eight years), but this did not translate into a mortality benefit, and the rate of DVTs was higher in the IVC filter group. The study has been criticised, but these criticisms do not mean that the filters work. Like the unblocking of arteries, it is another example of chasing the wrong outcome. IVC filters are meant to prevent death; whether or not they reduce PE rates (the proposed mechanism by which they save lives) is the surrogate, not the main outcome we are trying to prevent. People still look at things that way: they concentrate on the mechanism and on surrogate measures, not on whether the treatment achieves what it set out to achieve – in this case, to saves lives.

The article also noted that the regulatory approval of these devices is less than ideal. The first IVC filter was approved by the FDA in 1976, and all the subsequent devices were approved on the basis of being similar to the first one. None had evidence of effectiveness; after all, they are not drugs, they are only devices that are permanently implanted into the main vein in the body.

IVC filters are also associated with significant risks of harm, such as infection, dislodgement, migration, misplacement, blockage of the IVC, and need for removal.

As mentioned previously, when the evidence is not clear for a particular treatment, we often find that the use of that treatment varies a lot between hospitals or groups of doctors. Although tens of thousands of these devices are inserted each year in the US alone, there is significant geographic variation in the rate of usage. They may have some place in the rare patient who cannot take anticoagulants, but even in that case, the benefit is still theoretical, based on the same, admittedly attractive, biological mechanism.

The story of the IVC filter provides a good example of something that makes sense in theory, but fails the acid test, and for which there is an evidence–practice mismatch. It is another medical treatment whose benefit has been overestimated and harm underestimated. If you disagree with me and consider the device to be effective in some cases, please do a study to prove it.

SHOULDER SURGERY FOR IMPINGEMENT

When you raise your arm, the top of your humerus (the long bone in your upper arm), where the rotator cuff tendons attach, ‘impinges’ against your acromion, the outer end of the scapula (shoulder blade), in the shoulder joint. When this hurts, it is called impingement syndrome. ‘Decompressing’ the joint by taking some bone off the acromion (an ‘acromioplasty’) makes sense, and seems to work well. The operation has been around for a long time, and there have been many studies looking at different ways of doing this operation, but very few studies looking at whether or not it works better than not operating. Interestingly, all of the studies that have been done conclude that this operation adds nothing.

I did a lot of these operations in my training and got quite good at it. When I later saw patients with impingement, I knew what to do – operate. Fortunately for me, there were no randomised trials on acromioplasty when I started practice, so I could carry on doing what everyone else was doing. Fortunately for the patients, somebody questioned the role of acromioplasty and did the studies needed to determine the effectiveness of the procedure.

The role of acromioplasty for patients with impingement (with or without a rotator cuff tear) was examined in a Cochrane review published in 2008, covering the literature up to March 2006. Of the fourteen trials included, three specifically compared acromioplasty to nonoperative treatment in patients with impingement and one trial looked at the effect of adding acromioplasty to surgical repair of a rotator cuff tear. There was no significant improvement in pain relief or shoulder function from acromioplasty in any of the studies. Some patients randomised to non-operative treatment ended up undergoing surgery because of poor results, but they had poor results with surgery too.

It should be noted that one study used a placebo group, and that the placebo group did not do as well as the non-operative (physiotherapy) or operative groups, but the placebo group involved placebo physiotherapy, not placebo surgery.

Many studies have been published since that review, comparing acromioplasty to no acromioplasty in many different situations. The studies vary in several details, but not in their conclusions that acromioplasty offers little, if anything.

I should note that although the studies are unanimous in their finding that there is no advantage in performing an acromioplasty, there was usually a small benefit in the acromioplasty group compared to the non-operative group, just not a statistically significant benefit (that is, the difference observed may have been due to chance). Because of differences in the studies, the authors of the Cochrane review couldn’t combine the results (meta-analysis). It should also be noted that the methodology in these studies is generally poor, meaning that there is a risk of bias, which usually favours the intervention. So we don’t know if the small benefits seen were due to a real advantage of acromioplasty, due to chance, or due to bias.

A sham surgery trial is currently underway for acromioplasty. If it shows no advantage to acromioplasty, it might be time to put that one to bed, move on, and spend our research dollar on something else. Why are they doing the sham study if so many studies have already shown little or no effect? Because the procedure is still being performed, that’s why.

Sometimes, the acromioplasty accompanies a common shoulder procedure – repair of the rotator cuff tendons. Such tears are common, are usually degenerative (from wearing out) and get more common as you age. Often they are not painful. They are commonly treated with surgical repair, yet there is limited evidence of its effectiveness, with one recent study comparing it to acromioplasty alone and also to non-operative treatment that showed no advantage to repairing the tear, or doing the acromioplasty. More trials are underway. This is good news, not because I expect it to also show the surgery to be ineffective but because we are finally getting an accurate assessment of the comparative effectiveness of this operation, after half a century and millions of operations (about 300 000 per year in the US). I have been in the game for a long time, but it still staggers me when I see how long an operation can be in common practice before someone gets around to doing a proper comparative study to tell us whether the operation actually works.

FLOATING KIDNEY

I initially included this in the previous chapter, as part of the surgical scrap heap, mainly because floating kidney (or ‘nephroptosis’) was big in the late 19th century, but also because I thought that the condition was no longer taken seriously. In researching this however, I found that surgery for this condition is having a resurgence thanks to laparoscopic (keyhole) surgery.

Floating kidney was once very common (well, commonly diagnosed anyway), and there have been nearly 200 different operations described since the late 1800s, including removal of the kidney, but with most of them being forms of nephropexy (tying down the kidney). At the end of the 19th century, surgery for floating kidney was the most common procedure performed by urologists.

Floating kidney has been associated with multiple causes, and blamed for a wide variety of symptoms, including symptoms from damage to surrounding organs, nervous weakness, urinary tract infections, depression and irritability. The condition has been described as being present in up to 20 per cent of people without symptoms. Recent reports have also attributed high blood pressure and kidney stones to a floating kidney.

Floating kidney was initially diagnosed by feeling the abdomen, but with more modern imaging, movement of the kidney has been detected by dye injections, CT scans, ultrasound imaging and bone scans. The diagnostic criteria have been tightened (more than 5 centimetres of movement of the kidney between lying down and sitting), as have the classification of the condition and the indications for surgery. The diagnostic criteria have been set without any reference to how much a kidney normally moves, and without any correlation with symptoms.

Surgery for floating kidney (nephropexy) has always been controversial, with one early critic commenting that the biggest complication of having nephroptosis (floating kidney) is surgery. Even at its peak, there were sceptical urologists who denied the condition existed. Surgery was not the only treatment though, with good relief being demonstrated with the use of various corsets.

Controversy (and the high complication rate from surgery) led to a decline in the diagnosis and treatment of this condition after the 1920s. Since the 1990s, however, there have been many reports of nephropexy being done laparoscopically.

Recent reviews note the reappearance of the diagnosis of nephroptosis, and suggests that better diagnostic criteria, along with minimally invasive techniques, allows surgical correction to be performed in ‘selected’ patients. Some authors note that despite a lack of comparative studies and a lack of standardisation of the surgery, laparoscopic (keyhole) nephropexy ‘will remain the standard therapy’. A 2008 review (along with another review from 2004, and other recent reports, including one using robots) describe ‘clearly’ favourable results from surgery. I don’t buy it, for two reasons.

1   The diagnosis has never been established. I hear about movement, impaired kidney function, blocked flow, blood in the urine, and a myriad of ‘classical’ symptoms, but nothing has been produced that reliably attributes any symptoms to a kidney that moves more than 5 centimetres. We need to see a study showing that symptoms (whichever ones we choose) are more common in people whose kidneys move more than 5 centimetres, compared to those whose kidneys move less than 5 centimetres.

2   The treatment has never been validated. I’m not even talking about placebo studies; any comparative study would satisfy me for this particular topic. Compare it to psychological counselling or chiropractic for all I care, but compare it to something, otherwise we don’t know if the patients got better as a result of the surgery. And what about the abnormal kidney function? That made it sound serious, but in the study that quoted this, they didn’t even test kidney function post-operatively, so we don’t know if there was any improvement with treatment. Most of the time, we don’t even know if the kidney stopped ‘floating’ after the treatment. Doing a handful of cases and saying that most of the patients felt better afterwards just doesn’t cut it science-wise (although it is good enough for many surgeons).

So how do I explain the (roughly) 90 per cent favourable results with surgery? Firstly, I don’t even know how ‘favourable’ is defined or what is being measured, but either way, the answer is the same: most people (particularly those with vague symptoms and no clear diagnosis) get better after any treatment: just ask the homeopaths. The only way to reliably determine if the improvement was due to the treatment is to do an unbiased comparative study.

It is quite possible that patients with non-specific low back pain and lumbar pain are being diagnosed with this condition by virtue of the fact that they are sitting in the urologist’s office at the time. The same patient in a spine surgeon’s office might have been given a spinal diagnosis. This phenomenon of specialists tending to diagnose conditions that lie within their field is well known, and is covered in the following chapter under ‘The need to label’ (see page 212).

This is a great example of how the myths spread through a supposedly scientific community. Once a procedure has been done enough times and published, it is accepted as reasonable. Then all you need to do is keep changing the criteria for diagnosis and treatment (to explain any bad results from applying the previous criteria), and keep reporting ‘favourable’ results from patients in non-comparative studies. Easy. It appears that if there is no requirement or demand for high-quality evidence, no one rushes to get it.

TENDON RUPTURES

The collagen in our body degenerates over time; that is why we have wrinkles. It is also why we get tendon ruptures, like those to Achilles’ tendons, quadriceps tendons, biceps tendons and rotator cuff tendons, and why these ruptures are rare in young people.

Achilles’ tendon ruptures typically occur in people in their thirties and forties who may have some degeneration (weakness) in the tendon, and who play vigorous, high-acceleration sports. And when it tears, it tears with a loud snap and sudden pain, so much so that nearly every patient I have seen says that they turned around to see who hit them across the back of the heel and are surprised when they see that there is no one there.

For many years, the treatment of choice has been to repair the tendon surgically. This reflects our thinking in the non-medical world: if something is torn, we repair it. As usual, this superficial appeal, along with the observation that the patients seemed to recover pretty well, meant that we carried on fixing them and nobody asked the hard questions, like ‘Are the results better with surgery than with non-operative treatment?’ Fortunately, over the last decade or two this question has been asked, and answered.

Non-operative treatment with full weight-bearing in a boot with a raised heel results in similar functional outcomes to surgical treatment. The only difference between surgical and non-surgical treatment is that surgical treatment is associated with more complications (wound-healing problems, infection, nerve damage and adhesions) and more cost. Some studies have shown a slightly higher re-rupture rate with this type of nonoperative treatment, but some have not, and all the studies show a much higher complication rate with surgery. Either way, you can see that the decision between surgery and non-operative treatment is not as clear-cut as one would think.

When I started treating these non-operatively I was surprised at how well the tendon healed without surgery. Now I, and many colleagues, treat Achilles’ tendon ruptures non-operatively. What still surprises me is that many surgeons do not accept that non-operative treatment is a reasonable option. What surprises me less is that many patients do not accept that non-operative treatment is a reasonable option – such is the prevailing bias towards surgery as the answer to our physical breakdowns.

LAPAROSCOPY FOR BOWEL ADHESIONS

Laparoscopy is keyhole surgery of the abdomen in which a camera and instruments are inserted through holes in the skin, into the abdomen to see the structures within ( diagnostic laparoscopy) and to correct pathology where possible (therapeutic laparoscopy). In patients who have had previous pathology or surgery to the abdomen, adhesions can develop whereby loops of bowel can get caught up in scar tissue. If this causes an obstruction of the bowel, it can be very serious, but often people just have abdominal pain and this pain may coexist with adhesions without being caused by them.

Adhesions are common, and so is abdominal pain. Many doctors think that the adhesions cause pain, and recommend laparoscopic surgery to look around the abdomen and to ‘divide’ or unpick the scarred-down loops of bowel (the adhesions). Sounds reasonable enough, and some case series have shown improvement in over 80 per cent of patients undergoing laparoscopic division of adhesions.

Some doctors from the Netherlands suspected that the benefit might lie in the placebo effect, and the reassurance that the diagnostic part of the laparoscopy provided (if nothing serious was found), and that the adhesions (in the absence of a bowel obstruction) might not be the cause of the pain.

They conducted a study of 100 patients with adhesions and abdominal pain who underwent a diagnostic laparoscopy in which they excluded any other causes of pain. They then randomised them to having the adhesions divided (laparoscopically, at the same time) or doing nothing (only the diagnostic laparoscopy, leaving the adhesions alone). They followed the patients for twelve months and noted that there was no difference in the improvements in pain or quality of life between the groups. In other words, having the adhesions divided made no difference to whether or not the patients’ symptoms improved.

By this stage you can probably guess the difference that they did find. The group that had the adhesions divided were more likely to have a serious complication, including perforation of the bowel, an abscess, bleeding, and a fistula (look it up). None of the patients in the diagnostic group developed complications.

Although this example is in many ways similar to the others, it is worth summarising what this means. It means that well-intentioned, honest surgeons who do this procedure because they have seen previous patients improve afterwards, because it is a recognised procedure, because they believe it might help and is at least worth a try, and because they want to offer the patient ‘active’ treatment rather than reassurance, are, on average, harming patients and providing no benefit.

FRACTURE SURGERY

This one might be the hardest to swallow, and it is the hardest for me to write, because this is what I do – I am basically a fracture surgeon. The idea of fracture surgery (operating on bones to realign and stabilise them) makes so much sense on a superficial level that it is often difficult to talk people out of having surgery for their fractures. The appeal of putting broken bones back together was one of the reasons why I took it up as a specialty.

There is a common saying that ‘If it ain’t broke, don’t fix it.’ I use this phrase when patients come to me requesting surgery for something that they have seen on a scan, but without any physical signs or symptoms. But this phrase implies that the opposite is true: ‘If it’s broke, fix it.’ As with tendon ruptures, this kind of thinking works well in the physical world, but doesn’t necessarily translate into a biological organism. If your bicycle chain is broken, it will never work again unless you fix it. If your bone is broken, however, it is a completely different story.

Firstly, I will let you in on a little secret: we (fracture surgeons) don’t heal bones – your bones heal themselves. I liken it to a cut in your skin. Stitching it together doesn’t heal it – it just puts the skin closer together so that when your body heals the cut (which it would have done without the stitches), the scar will be smaller. For bones, we can influence the position in which your bones will heal, but all we are really doing is holding them in that position while the body does its own healing.

‘How’s it gonna heal without surgery?’

This question often arises when I’m talking to patients with broken bones and torn tendons and ligaments. The question comes from the rule-of-thumb that broken things generally need to be fixed, mixed with a general overestimation of the effectiveness of, and need for, surgery to fix our physical problems.

Normally the conversation takes place with a patient in my consulting room with a recent fracture, and an X-ray on the board showing the two ends of the bone in less than perfect alignment.

I might start addressing this by (hypothetically) directing them to the nearest natural history museum, where they can see dinosaur skeletons with healed fractures in the bones (I also have a nice slide of this that I use in talks). This illustrates the fact that fractures have been healing since before there were any humans. I also point out that sometimes, by operating on fractures (and removing the blood clot that will later turn into bone) we can even decrease the chance of it healing.

I then explain that the main reason we operate is to adjust and hold the alignment, not to make it heal. Again, though, there is an expectation that the alignment should be perfect (like a jigsaw puzzle). A lot of doctors feel the same way, but unless the alignment is absolutely crucial to the eventual function of the bone (like when fractures involve the surfaces of joints) then we only need to get them into rough alignment. As long as the final result will not lead to any loss of function, there is no need to operate and expose the patient to the risks and costs of surgery – what we refer to as ‘treating the X-ray, not the patient’.

This is a particular problem in children with fractures, where you have a combination of concerned parents, and a patient who can actually remodel (reshape) their bone such that quite marked deformities can reshape back to normal over the course of a year or so. Surgery is often not required in children’s fractures and far greater deformities can be tolerated with excellent functional and cosmetic results, which is a bit paradoxical because you would think that we would be more aggressive in getting children’s fractures aligned.

But at the heart of this question is a reflection of society’s overreliance on surgery as the preferred way of fixing the physical breakdowns that occur in our body – we look at the body like a car in need of a mechanic. And I must admit that it still surprises me when I discover that treating the body like a machine, by removing torn cartilages, repairing torn tendons, unblocking arteries and veins and catching clots in a net, patching holes in the heart, either doesn’t work, or doesn’t work any better than leaving it to the body to sort it out.

So what fractures don’t need treating? Lots of them. Some are treated because that is what is often done, and nobody has done the comparative trial to see if it is necessary (an evidence gap), and some are treated even when evidence exists that there is no significant benefit from surgery (an evidence–practice gap). I have chosen a few examples, but only ones that have been subject to trials comparing them to non-operative treatment. I won’t comment on fractures that have never been subjected to such trials, except to say that it is an indictment on the medical community that the trials have not been done.

Shoulder fractures

Fractures that occur at the upper end of the humerus near the shoulder (called humeral neck fractures) are common. They are often treated with surgery, despite a lack of supporting evidence for this, particularly in older, osteoporotic patients. According to a recent study, it is possible that most of these fractures don’t need surgery, even in young patients. This was big news, but it really only provides more evidence to support the previous studies. And being big news doesn’t mean that this research will jump the gap from research into practice and influence the decision making of the end users – the patients and their surgeons.

Humeral neck fractures are one of the most common fractures in the elderly, but they can occur from falls or accidents at any age. They come in many shapes and sizes. The ones that are not very displaced (not very far from their original position) do not need surgery. The ones that are associated with dislocations of the shoulder joint are usually treated surgically. However, for all the ones in between – the displaced fractures – the decision making is not so clear.

Like a lot of other fractures, we know that we can make the X-ray look better if we operate to put the broken pieces back in alignment, or if we replace the broken bits with an artificial shoulder joint. This is what is commonly done for displaced fractures, but are we just treating the X-ray and not the patient?

There has always been some debate about the advisability of surgery in older patients. The advantages of realigning the bones have to be balanced against the risk of failure due to the screws coming loose in the soft bone, infection, further fracturing, dislocation of the joint, and other general surgical complications, all of which are a little more common in older patients.

There have been several randomised trials comparing surgery to non-operative treatment for displaced fractures, going back to the 1980s. In a review of these studies, it was shown that there is very little evidence that our attempts to fix things up with surgery make any difference to the patients in terms of their pain or shoulder function. In fact, the only difference is that surgery tends to lead to more complications and more secondary surgery than non-operative treatment. These studies were mainly on older patients. They are a little dated and they are small studies, and they have not really influenced practice.

There has always been considerable practice variation, with some surgeons treating many of these with surgery, and other surgeons treating most of them without surgery. And the decision making for each type of surgeon was not based on solid science – more of a feel. Over the years I have seen young surgeons who were very keen to fix these fractures surgically, thinking that they will make the patient better by making the X-ray better, and then I have seen these surgeons reverse their practice after a few unfavourable cases and go on to treat most of them non-operatively later in their career.

Despite evidence showing a lack of benefit with surgery, practice still varies between surgeons and as long as newer implants are being introduced, there is always someone who believes that the new implant will be the answer to this problem. The introduction of ‘fixed-angle’ or ‘locking’ screws in plates was an example of this. It was widely taken up but has failed to deliver (proven) benefits to patients.

Even though the studies up until recently (that show surgery to be of no benefit) have not been without flaws, that shouldn’t allow us to assume that the results from these studies are all wrong. There are still no good studies supporting surgery.

The recent study came out in 2015 and provided good evidence that surgery is not necessary for most of these displaced fractures. There are two things about this study that I would like to highlight. Firstly, it is a good study that is likely to be generalisable to practice in most developed countries. This is because it is a ‘pragmatic’ study (my favourite type), because it took all comers and left it to the surgeons as to what operation they thought would be best (in the group that was randomised to surgery), therefore reflecting real life. Secondly, unlike the previous studies, it recruited patients aged sixteen and over, not just older patients. I thought this was a big call, because the assumption has always been (admittedly in the absence of evidence) that surgery was beneficial for younger patients, in whom there was a lower likelihood of the implants coming loose.

They recruited 250 patients from thirty-two centres across the UK with fractures that the surgeons thought would benefit from surgery, and then randomised them to having surgery or non-operative treatment. They had good follow-up and measured the results up to two years, and they only excluded very bad fractures (dislocations of the joint or cases where the bone was pushing under the skin). The upshot? There were no meaningful differences between the groups in the outcomes measured (pain, shoulder function, quality of life, etc.), including in the younger patients, where, if anything (and surprisingly), the non-operative group did slightly better.

The lure of newer implants, of making bones line up and of actively doing something has led doctors to treat many of these common fractures with surgery, despite a lack of evidence of any benefit, and some evidence of a lack of benefit. Now there is high-quality evidence that surgery is of no benefit for most of these fractures. I am interested to see if this will change the way people treat these fractures. I think it will, but these things take time.

Ankle fractures

Our research unit did a survey of orthopaedic surgeons in Australia, to look at how they would treat a series of common fractures. We provided what we thought were typical X-rays of common fractures and asked if they would prefer to treat them with surgery or without, and if they chose surgery, what operation they would choose. We found considerable practice variation, with, on average, about half of the surgeons treating the fractures with surgery and half without. The factors that influenced the decision making were surgeon age and sub-specialty training, such that the hand specialists were more likely to treat the hand and wrist fractures with surgery, the shoulder surgeons were more likely to treat the shoulder fractures with surgery, and so on. With respect to age, older surgeons were more likely to treat the fractures nonoperatively. Interestingly, the older surgeons said that the young surgeons were too aggressive and would learn, whereas the young surgeons said that the older surgeons were out of touch and too cautious.

The ankle fracture case that we showed was the most common type of ankle fracture, which involves a fracture of the little bone of the lower leg (the fibula), with some displacement of the bone, but without displacement of the ankle joint. The results of the survey led us in the orthopaedic community to design and conduct a multicentre randomised trial comparing surgery to nonoperative treatment (full weight bearing in a walking boot).

Unsurprisingly (at this stage in the book anyway), surgery did not lead to any benefit regarding pain or function in the ankle, but (again, unsurprisingly) it did lead to more complications (wound healing, infection and extra surgery). Surprisingly, thousands of these fractures have been treated with surgery for decades, and still are, at enormous cost and some risk, but it is only lately that anyone has done any quality research to find out if the operation is effective or necessary. Not a good advertisement for the science of medicine. It is, though, a good example of the double standard that doctors display when they criticise alternative medicine as not being effective because of a lack of proper randomised trials, yet assume that what they do as doctors is effective, without the same randomised trials that they demand of others.

Spine fractures

One of the most common spine fractures is a so-called ‘burst’ fracture. This usually occurs in the lower-middle part of the back and is due to a fall from a height, like jumping off a balcony. The vertebra flattens like a pancake and expands out (bursts). This may make the spine less stable and there is often pressure on the surrounding nerves. This makes everybody scared, and when they are scared, they tend to go to surgery to make themselves feel safe. I spent a lot of time in my training operating on these fractures – putting in rods and screws to stabilise the vertebrae above and below the fracture. Many people have created criteria for deciding on which fractures need surgery, but (again) often without testing whether or not patients do better with surgery. The criteria are based on theoretical concepts of stability and possible nerve damage.

One of our students reviewed the randomised trials on this subject and found that when surgery was tested against no surgery, the results are nowhere near what most people expect. Firstly, the risk of neurological damage is no greater without surgery. And as for so many of the examples in this book, the risk of complications, the need for future surgery and the cost are all higher with surgery. The overall pain and function are no better with surgery, although there are some differences here between separate studies. However, the most surprising finding is that the deformity is barely different between surgical and nonoperative treatment. These fractures often cause the spine to bend or collapse forwards (a deformity called kyphosis), and one of the indications for surgery is to correct that deformity and to prevent it from getting worse. Yet, according to systematic reviews of the topic, the difference in kyphosis between surgical and non-surgical treatment is only about 5 degrees (probably not a visible difference), and furthermore, there is no correlation between the degree of kyphosis and the level of pain or function that the patient has.

The reviews on this subject have been restricted to cases where there has been no nerve damage (there may be compression of the nerves, but they are still working). This is because the presence of nerve damage is often a criteria for surgery, supposedly to decompress the nerve. Superficially, this sounds reasonable. However, surgery to undo nerve damage in spine trauma is not really a thing; there is a reasonable argument that the nerve damage is due to the initial injury, rather than any ongoing compression. This fits with the facts that surgery for paraplegia does not resolve the paraplegia; that there is very little correlation between the degree of residual nerve compression and the extent of any nerve damage; and that the compression (usually measured as narrowing of the spinal canal) resolves (the canal widens) over time anyway, even with non-operative treatment.

In short, surgery to stabilise the common burst fracture in the area of the spine between the chest and the abdomen (the thoracolumbar spine) increases the risk of complications, the cost, and the chance of having further surgery. It straightens the spine slightly more than non-operative treatment, but that doesn’t correlate with better pain or function outcomes. And the assumed benefit of surgery in cases with nerve damage is based on little more than theory and is untested against nonoperative treatment in a direct head-to-head trial. This type of surgery is an example of ‘When in doubt, operate’ – the reason behind much of the unnecessary surgery done today.

WHAT ELSE IS THERE?

I had to draw a line somewhere when writing this chapter. I did that by trying to stick to surgical procedures that probably have a strong placebo effect, rather than drifting into the world of unnecessary surgery, although that line is not clear. For those who think I’ve been a little hard on the orthopaedic surgeons, as I said before, it is because that is what I know best. I could have listed many more orthopaedic procedures that are ineffective, but if I dug any deeper into orthopaedics I would soon be getting into the kinds of procedures that I currently perform (see the breakout below, ‘A confession’).

I actually think that orthopaedic surgeons are doing more to correct this problem (by performing the studies that fill the evidence gaps) than any other surgical specialty – but more on the solutions in Chapter 9.

A CONFESSION

I perform surgery that doesn’t work. I state this in case any readers were thinking that I considered myself blameless in all of this. Having said that, I currently perform much less ineffective surgery than I used to. Like many of my colleagues, I had to see a few patients treated successfully without surgery and make a few mistakes along the way before I got better at picking when to operate. There is a saying in surgery: any surgeon can operate; a good surgeon knows when to operate, but the best surgeons know when not to operate.

In my career, I have done surgery for ‘ununited’ fractures that had already healed, removed implants that were not causing a problem, fused sore backs and ’scoped sore knees. I have even re-operated on people with ineffective procedures after the first ineffective procedure was, well, ineffective.

I will go one further: I have operated on people that didn’t have anything wrong with them in the first place. This happens because if a patient complains enough to a surgeon, one of the easiest ways of satisfying them is to operate. You can convince yourself that there must be something wrong for them to complain so much, even if the tests are normal. I have learned that there are many unhappy people out there with severe symptoms who have nothing physically wrong with them (nothing that is causing the symptoms anyway) – they don’t prepare you for that in medical school. These patients are not malingerers (those are easy to spot, and rare), but people who are caught in complicated compensation and legal systems, who have been wronged, or have other psychosocial factors that are manifesting with physical symptoms. For example, the biggest predictor of reporting back pain at work is job satisfaction. And you wonder why surgery doesn’t work for back pain.

And if you are wondering how doctors can treat people with no identifiable pathology, they do this by first labelling the patient with a condition, a topic covered on page 212.

INVASION OF THE ROBOTS

Surgeons are very keen on robotic surgery. I could say they are doing it for the reputation and the referrals, but this would be cynical rather than sceptical, so I will simply say that they are not necessarily doing it to benefit the patients. They may think they are, but I am not aware of any evidence that patient-reported outcomes are better with robotic surgery. I am, however, aware of empirical evidence that robots cost a lot, because I have seen the bill.

Robotic surgery involves a large integrated unit consisting of cameras and robotic arms that the surgeon controls remotely from a console. The surgeon can see what the camera sees, and can control the arms to cut through tissue, cauterise blood vessels and suture tissues together. This allows finer movements in confined spaces, and hopefully less ‘exposure’ or cutting to get into the place you need to be.

It turns out that robotic surgery is yet another example of something that sounds good, with some research showing improvements in some aspects, but with the whole thing falling down when it comes to improving patient health.

Systematic reviews of the clinical research on robotic surgery are plentiful (although not nearly as plentiful as websites promoting robotic surgery), so I looked at the most recent reviews for the most common applications.

•   For bariatric surgery (for obesity), a recent review showed that there was no clinical benefit from robotic surgery.

•   A recent review on robots in urological surgery, like prostatectomy, showed some improvement with certain outcomes (length of stay and blood loss), but not with patient health. And the best news I can get out of a review of robotic prostatectomy from highvolume centres is that it is ‘safe’.

•   A 2011 review on robotics for gynaecology showed no clinical benefit, and a Cochrane review on the same topic didn’t help the cause either.

•   Three papers, all from 2012, only showed that robotic surgery was feasible for colorectal surgery, but with no clinical benefit.

•   For cholecystectomy (removing the gall bladder), a rigorous Cochrane review showed that having a robot do your operation ‘appears safe but does not offer any advantage’.

It is amazing how awestruck we are when we see high-tech wizardry, and how we assume that it must be better than whatever it is that we are doing now. I suggest that you ask for the evidence before paying any premium for robotic surgery.

An example of the bias towards robots was highlighted by a fellow blogger, the Skeptical Scalpel, who commented on a popular YouTube video of a surgical robot folding a paper plane. Amazing, right? Well, yes, and many agreed, but the robot takes forever to do it, makes a few mistakes along the way and, most importantly, makes a plane that heads straight for the ground. Again, people are impressed by the idea and the potential; they are ready to believe that it is better, and tend to ignore important evidence in plain sight (the crashing plane) that is contrary to their expectations. We should be seeing the robot in that video for what it is – error prone, slow and harmful – not for what it could be.

PRACTICE VARIATION

By looking through reports of practice variation in surgical procedures worldwide, we can get an idea of what procedures might be done unnecessarily, and by looking at variation in any new technology (like robotic surgery), we normally find strong uptake of new procedures that seems to run ahead of any supporting evidence. For practice variation, the procedures that often pop up with high rates of variation are prostate surgery and even the ubiquitous hernia repair. I have no doubt that some hernias are painful or uncomfortable and benefit from surgery, but I see a lot of generally unhappy patients with non-specific pain and no lump who have been told they need a hernia repair.

Why is the rate of caesarean section nearly 50 per cent in Brazil, but less than 20 per cent in Scandinavia, Japan and France? Why are there nearly 400 000 (one in 1000 population) spine fusions done in the US every year, but only one tenth of that rate in the UK? Some of the variation may be due to differences in the people themselves, but not much of it.

When we see big variations that cannot be explained by differences in the local populations or underlying rates of diseases, it means somebody is wrong. Either the rates in one place are too high or the rates in the other place are too low. Or both – but it still means that somebody is wrong. For example, it is likely that the caesarean section rate in many countries is too high, but in some countries (there are many with rates less than 10 per cent), the rate may be too low.

The history of practice variation goes back a long way, to a surgeon named James Alison Glover in the UK, who, in the 1930s, noticed considerable variation in the rates of tonsillectomy between schools. He could not attribute this to any social disadvantage or differences in the rates of disease (tonsillitis), and suggested that the difference was due to surgeon preference.

An interesting aside, still on the topic of tonsillectomy, also comes from the 1930s, but from the other side of the Atlantic. In New York at that time, tonsillectomy was considered a public good, so the American Child Health Association devised a program to make sure that no child was overlooked. They sampled 1000 school children, noting that 60 per cent had already had a tonsillectomy. They sent the other 40 per cent to a doctor to see if they needed the procedure. The doctor suggested that 45 per cent of those needed a tonsillectomy. Just to make sure, they sent the remaining children (who were not recommended tonsillectomy) to a second round of doctors, who suggested tonsillectomy in 40 per cent. Still not satisfied, they sent the handful of children left with their tonsils intact to a third group of doctors, who suggested tonsillectomy in 44 per cent. After that, there were only 65 children left (out of the 1000) who had not had tonsillectomy recommended. Perhaps they should have been sent to a fourth group of doctors? I can guess what would have happened. Unwittingly, this program showed up the practice variation and poor science behind patient selection around tonsillectomy.

More recently, others have taken up the task of measuring and explaining practice variation, most notably in the US, at Dartmouth University. Their website has variation ‘maps’ that visualise variations in clinical practice. The OECD has also done some work on practice variation for common procedures, which can be viewed on their website.

Are these placebo procedures, or just unnecessary or ineffective operations? The answer is that it all starts to blur into one if you accept that the reason for doing these ineffective procedures is because of their perceived (placebo) effect. Whether this is due to a true placebo effect or not can only be determined by comparing the procedures to placebos, and whether or not you define this as a placebo effect, as a meaning response, or attribute it to things like natural history is beside the point. The point is that surgery is being done that is either not effective or is less effective than we suppose. It is surgical decision making that is not based on the true effectiveness of the procedure, and when we are talking about something as costly and potentially risky as surgery, that is not good enough.

7

WHY DO WE STILL DO IT?

REASONS BEHIND THE PERSISTENCE OF SURGERY THAT IS NOT EFFECTIVE

THERE ARE MANY reasons why we use ineffective treatments. Many have already been touched on, but I cover all of the reasons in this chapter. Although I have divided the chapter into subheadings, those subheadings are arbitrary, and there is considerable crossover between them. Many of the reasons are related to human nature, covered in the first section, and the boundaries between these are blurred. The reasons include the desire to treat (rather than not treat, which was touched on at the end of the last chapter), bad science, legal considerations, financial incentives, the resistance to placebo surgical trials, and the ethical environment in which all of this takes place.

HUMAN NATURE

One reason why we still do procedures without good evidence (or even with good evidence that it doesn’t work) is because we are humans. It is easy to be human and assume cause and effect when we see an association, and to pick out the observations that confirm our beliefs. Being a scientist is a lot harder. One single logical fallacy – post hoc, ergo propter hoc (it follows, therefore it is because of) – is responsible for the perpetuation of most healing crafts, including medicine. It is also largely responsible for many superstitions, customs and religious practices.

It is also human nature to believe what we wish to be true. If we expect a treatment to work, it is more likely to be perceived as working – we look for confirmation of our beliefs and expectations and when we see some (any), we use it as ‘evidence’ of the causal association we assumed in the first place. Similarly, we tend to disregard, or explain away, findings that do not fit our preconceived idea. In this way, treatments can become self-fulfilling prophecies. As one of the greatest medical sceptics, Ivan Illich, once said about medicine being akin to magic: ‘Magic works if and when the intent of patient and magician coincides.’

We are also gullible and will make up plausible causes when one is not available – preferably one that also fits our scientific knowledge. This is why I have distrust of biological explanations for treatment effects – what we call a biologically plausible mechanism. A biologically plausible mechanism is one of the requirements for causation; if you don’t have one, you’re in trouble. But that is not the problem; the problem is that there are too many of them, and they are too easy to manufacture. So many apparent treatment effects have been observed, assumed to be true, and then explained by a biologically plausible mechanism. When the treatment is later shown to be ineffective, the mechanism is discarded. Not having a plausible mechanism may be a problem, but assuming that the mechanism is true without proper testing is a bigger problem. Biological mechanisms are a bit like the ‘diagnostic’ labels covered in the section ‘The need to label’ later in this chapter (see page 212): easy to make up, based on what the labeller knows, and scientific-sounding, but not reliable.

Another human trait is to be influenced by recent experiences. For example, obstetricians who attend a birth with complications are significantly more likely to recommend and perform a Caesarean section in their next fifty cases, showing how we are influenced by recent experience and how we tend to practise defensively.

Patients are human too, and they usually absorb the overestimation of benefit that prevails in the medical community. They assume that doctors help, they don’t harm; that receiving medical treatment is better than not receiving treatment. This might account for our apparent disinterest in reports of harm from medicine. There have been several such studies from the US, Canada, Australia and New Zealand, each reporting considerable harms from medical interventions, but they have not caused the reaction that I would consider proportional to the harm. If any other industry or political group had caused such harm, we would never hear the end of it.

The reports of medical harm have been criticised, and there is certainly some degree of uncertainty around the numbers, but the numbers are so large that even accounting for some margin of error, you would have to prove, by performing another (better) study, that the numbers are false before rejecting them. The results should be debated; they should not be dismissed. This is covered further in Chapter 9.

Maybe the public cannot be blamed for overestimating the benefits and underestimating the harms of medicine; they are only responding to what the media and the medical community is feeding them. But I expect more from the doctors, and part of the problem is that the doctors themselves rely on human nature, not science, to make decisions.

SURGEON VERSUS

PATIENT PERCEPTION

In a study of over 330 patients undergoing hip or knee replacement surgery for arthritis in four different hospitals (two public and two private), our researchers rated the outcomes of the surgery by asking the patients, and asking their surgeons. At twelve months after the surgery, overall satisfaction rates were high, but there was a clear difference between the surgeon ratings and the patient ratings. The surgeons considered the operations to be successful about 95 per cent of the time, whereas the patients had 90 per cent satisfaction rates using the same questionnaire.

We have done similar research after leg fractures. Patients rated their satisfaction with progress at six months as 75 per cent; surgeons rated it as 88 per cent. At the same time, patients rated their overall recovery as 44 per cent; surgeons as 67 per cent. It appears that the ratings were influenced by different things. The surgeons considered the surgery to have failed if the fracture had not healed. Patient satisfaction was linked to non-fracture factors, like gender, and blaming someone else for the accident.

Similar research has shown that doctors tend to overestimate the results of their treatment compared to the patients receiving the treatment. The problem I have with this is that the decision making in surgery is often done by the surgeon, based on their perception of the success rate of the operation, not on the patient’s perception of success.

The lack of reliance on science by doctors is at least partly due to a lack of understanding of the scientific method in the medical community. There is some criticism of medical (and particularly surgical) training that it is too much of an apprenticeship – observing and doing what your teachers do – and that there is a lack of teaching of things like critical thinking. Consequently, doctors fall into the same logical traps as the public, and overestimate the benefits from medicine, and, in particular, surgery.

And sure, the science is often wrong, but it does tend to correct itself: cumulative research and the new knowledge that comes from it moves our estimate of what is going on gradually closer to the truth, without necessarily reaching it. Our ability to estimate the true effect of any treatment is related to the scientific quality of the research – this is why simple case series might make something look good, but randomised, blinded testing against placebo might reveal a different result. Therefore, one of the main obstacles to our pursuit of the truth is the lack of high-quality scientific research in the field of surgery. This is the previously mentioned ‘evidence gap’, and unfortunately there are many procedures being performed today that fall into that gap. A common statement used by surgeons in response to an evidence gap is to say that a lack of evidence does not equate to evidence of a lack of effectiveness. In other words, if there is no evidence out there, then we don’t know that it doesn’t work. I address this comment in more detail in the breakout below.

When there is an evidence gap (a lack of rigorous comparative trials) there is often still some evidence, but evidence of lower quality: case series, case reports, opinion pieces. These tend to be biased towards the treatment, and this is another reason why treatments continue.

A LACK OF EVIDENCE OF EFFECTIVENESS IS

NOT EVIDENCE OF LACK OF EFFECTIVENESS

This phrase is commonly used to justify surgery. It means that just because a certain procedure hasn’t been subjected to a rigorous comparative test (‘lack of evidence’), it doesn’t mean that it doesn’t work (‘lack of effectiveness’). However, this phrase is often used incorrectly, for several reasons.

Firstly, while it is true that a lack of evidence does not mean that the treatment is not effective, it very often means exactly that. How many times (in this book alone) have we seen procedures that were assumed to be effective, only to be shown to be ineffective on proper testing? It is a reflection of the prevailing bias towards the effectiveness of surgery that we can get away with assuming effectiveness when we have never put the treatment to a proper test. We wouldn’t let an alternative medicine practitioner get away with that kind of reasoning. As scientists, we shouldn’t let ourselves get away with it. No other field of science would allow such an assumption.

Secondly, while it is true that a lack of evidence does not allow us to assume a procedure to be ineffective, the opposite is also true: it does not allow us to assume that it is effective – which is usually what the person using this phrase is implying.

There is often a mistrust of the evidence (when it is there), sometimes due to a lack of understanding of the scientific principles, but also because the findings of the study don’t fit in with the surgeon’s particular mindset, his or her view of the world. There are ways of rationalising this, of dealing with this cognitive dissonance. One way is to criticise the validity of the research; the other way is to criticise the applicability of the research to the surgeon’s practice.

COGNITIVE DISSONANCE

Cognitive dissonance refers to the mental discomfort one feels when confronted with evidence that contradicts a previously held belief. It is entirely understandable, but what is interesting is how people deal with this discomfort – how they attempt to reduce the conflict. Some people can simply ignore or not seek out this new information; some can dismiss it on spurious grounds, perhaps by attacking the person who delivered it, or by making fun of it, or by concluding that the information is wrong or not applicable to them.

What we should do when faced with such a situation is to go through all of the evidence in an objective, rational way to determine (using science, logic and rational thinking) what our best estimate of the truth really is. But to do this, one needs to have knowledge and training of critical thinking and the scientific method, and to accept that we may be biased in the first place.

Think about how hard it is to convince an alternative medicine practitioner or religious person that a particular belief cannot be true, based on scientific evidence. It’s not much different with medical practitioners. Just think about the doctors who were faced with evidence against bloodletting all those years ago – they didn’t accept it.

The evidence had to be wrong; it was flawed.

A surgeon may criticise the validity of the study by picking any aspect of the study that might be prone to bias. As there is no perfect study, this is fairly easy: the study was too small, they didn’t measure things properly, their follow-up rate was not very good, etc. But we need to be careful when doing this; if a methodological flaw is all that is needed to completely dismiss the findings of a study, we would have nothing to rely on. The question should be: how would that potential flaw have affected the study, and did the authors look at this? For example, studies are often criticised for not recruiting many participants from the potential pool of patients. But if we look at the patients that were selected, and decide that they are representative of the pool, then that might not be important. And anyway, this type of selection bias does not affect the internal validity of the study, of what the researchers did and what they found with that group of patients.

Another way to criticise research is to point to the applicability (or lack of it) to one’s practice. Criticisms like ‘Those guys are not as good at that procedure as me’, ‘They do a funny variation of that procedure’, ‘My technique is better’, ‘Their patients are not as bad as mine’, ‘In my patients this procedure works much better.’ This is also the kind of thinking behind the observation that, on average, most people rate themselves as being above average. Doctors are not immune to this: there is one study showing that doctors who made a diagnosis with 88 per cent confidence were right only 20 per cent of the time.

Apart from pointing out that most surgeons think that they are better than most other surgeons, the only answer I have for those who criticise the research in this way is for the surgeon to do a study themselves. Pointing out the flaws in a study that shows a certain procedure to be ineffective does not allow us to assume that it is effective in someone else’s hands. That somebody needs to prove it by doing their own study.

INERTIA, AND THE NEED TO ACT

There is something called inertia – the tendency for things to go in the same direction unless acted upon by an external force. This has also been termed ‘status quo bias’ – our tendency to believe that what we are doing now is best. This is a strong barrier to change in medicine, particularly in the field of surgery, which is traditionally very, well, traditional. It is one of the reasons why practice does not change, even in the face of good evidence that a treatment is ineffective.

The need to act is a strong driver of overtreatment in medicine. There is an impetus to treat, rather than not treat, any patient who presents to us with a problem. The desire to treat is innate (we want to help, and be seen to be helping) and this is separate from (but additional to) other biases, such as our overestimation of the effectiveness of the treatment we use, safety in sticking with common practice, and reliance on tradition.

Not treating someone is interpreted as doing nothing, but calling it ‘nothing’ is misleading because it can mean using some other form of (non-operative) treatment, closely monitoring the patient, and providing reassurance and education – which isn’t really the same as doing nothing.

Unfortunately, the bias to treat (over not treating) is pervasive within society and therefore extends to the law (a reflection of society’s values). If a patient has a bad outcome, a surgeon is less likely to be found negligent if surgery was provided for the condition, than if he or she advised against surgery. It is the difference between saying ‘at least they tried’ and saying ‘they didn’t do anything’. There is also legal safety in doing what is expected; what everyone else is doing.

In my medico-legal work I have seen many cases where surgeons have been sued for not operating. That’s reasonable if the evidence says that they should have operated, but often it is one of those areas where there is no good evidence either way, or conflicting evidence. This is where the testimony of the expert who always operates stacks the odds against the surgeon. Sadly, though, I have also seen cases where surgeons have been sued for not operating when the evidence is clear that there is no benefit from surgery. It is a reflection of the strength of the bias towards surgery in society that a surgeon could be sued for not operating when high-quality scientific evidence supports that decision. This is a bias that I am attempting to ‘straighten’ in this book.

My medico-legal practice has also taught me that the legal system has little room for science, possibly because they are not trained in the scientific method and therefore rely on expert opinion. Expert opinion is the lowest level of evidence in science.

Language is also partly responsible for some of the overtreatment in medicine. The term ‘conservative treatment’ used to mean mainstream treatment; now it means old-fashioned or overcautious treatment, and it can be used to imply reluctance, fear or lack of competence in the face of new or high-risk interventions.

Experienced surgeons can easily make an operation seem desirable with their use of language; surgery is an ‘easy sell’. Consider this example: a young man presents to a surgeon after a fall with a displaced fracture of the clavicle (collarbone). If I (the surgeon) wanted to sell the surgery, I would not be lying if I said: ‘We have two treatment alternatives: we can fix the fracture or we can leave it.’ I use the term ‘fix’ to mean surgically setting and stabilising; the patient understands ‘fixing’ to mean ‘making good again’. To the patient, ‘leaving it’ means not treating it, thereby not ‘fixing’ the problem. I could inform the patient of the relative risks and benefits of ‘fixing the fracture’ (surgery) and ‘leaving it’ (non-operative management), but who wouldn’t choose the former when put to them in such a way?

The lottery mindset is another driver of action over inaction. ‘I know the chance is slim, Doc, but let’s go for it’, is how one author (Nortin Hadler) has put it. People will go for the aggressive treatment with the one in 1000 chance of pulling off something great (a chance that might be closer to one in a million, or zero in a thousand), and accept all the associated risks, rather than leaving the condition to the vagaries of nature. Doctors play on that mindset. For spine fusion surgery in patients with back pain, the doctor could spell out the fact that studies have shown no difference between surgical and non-operative treatment, and that only a proportion of patients improve. And then go on to point out that they won’t know if the patient will improve until after the surgery. People want to win the lottery – that’s why they buy tickets with almost no chance of winning. People want surgery to work – that’s why they take the risk. If the outlay (risk) is small, like a lottery ticket, this might be considered reasonable, but in surgery, the outlay (risk and cost) is great.

Currently, doctors appear more likely to be acting in the best interest of the patient if they act; even more so if they act aggressively. It also appears to be an admission of failure or weakness if the doctor does not (or cannot) diagnose or treat a patient, regardless of whether or not it is in the patient’s best interest. This drives one of the most irksome paradigms: that of the ‘surgeon-as-hero’, in which aggressive surgeons are held up as heroic, and cautious, conservative surgeons are considered cowardly.

‘At least we tried’, is what the family will say after their relative died undergoing ‘heroic’ surgery. Some surgeons are famous for being aggressive and doing operations that most other surgeons wouldn’t touch. This is thought to be because the other surgeons are not brave enough, and only this surgeon has the courage to push the envelope. This is rubbish, and if you look beyond the superficial you often find that the heroic surgeon will have bad results, or, more often, their results will not even be published, let alone compared to less heroic treatments in a proper trial. The reason why no other surgeons are doing the heroic procedure is often because they think it is a bad procedure.

I would argue the opposite: that it is harder, and possibly more courageous, to treat patients without surgery, particularly when surgery is thought to be helpful and many others are doing it. My practice would be easier if I simply operated on patients in which there was some doubt about the effectiveness of surgery. I would not get criticised (because others are doing it, and ‘at least I tried’); I might be less likely to be sued; I wouldn’t have to spend so much time explaining myself; and, of course, I would be paid a lot more.

For health workers, there is a need to be useful; they need to matter. Telling a patient that treatment is not effective is not supporting your practice or that of your colleagues. For some practitioners, like general practitioners, there may be many alternatives. For surgeons, there is surgery. All specialists tend to recommend the treatments that they know best, and even to diagnose complaints as conditions with which they are familiar. An overview of this tendency is provided in the box below.

It is also easier for specialists, like surgeons, to provide treatment because that is what is expected of them. It takes less time, and provides more income, to book a patient for an arthroscopy of the knee than to counsel them on the likely ineffectiveness of the treatment, and tell them to continue taking the pills. Particularly if they were referred from a regularly referring local doctor specifically for the procedure, and if the patient wants it done.

THE PATIENT’S PERSPECTIVE:

‘AM I EXPECTED TO LIVE WITH IT?’

This is one of the hardest questions for a treating doctor to deal with, and often the easiest way out is to do something, regardless of its effectiveness. If you are a surgeon, that usually means to operate. The question is often raised in relation to pain, but the link between pain and hard, physical signs (like findings on physical examination and on imaging studies – the kinds of things we target with surgery) is weak, at best.

Surgeons often operate because they feel they have little alternative – there is a perceived need to treat, to intervene, and limited alternatives. But not operating on someone does not mean you are not treating them; sometimes the best way to treat them is to not treat them. However, that doesn’t exclude educating or reassuring them.

It should also be pointed out that although there are many non-operative treatments for pain, their effectiveness varies and sometimes they reinforce the underlying problems, and often reassurance and education are bypassed in the enthusiasm to start the treatment.

There is no simple answer to the question above, but there is a hard answer. Firstly, it is the wrong question. The question to ask a doctor is, ‘I have this problem. Is there anything you can offer me to improve my situation?’ If the answer to that question is ‘No’, the original question usually follows.

The patient needs to be reassured that the pain will not necessarily get worse, to understand that it can be relieved (at least partially) with mild painkillers and other methods, and that their perception of the pain can be adjusted upwards or downwards by their psychological state. It is important that the patient understands their role in managing their condition. Worrying about pain, and often not so much about the pain but about what it might mean, what it means for one’s future, one’s job, etc., can lead to an oversensitisation – to amplification of the pain.

I am constantly surprised by the difference in pain perception between individuals with similar injuries or diagnoses. I understand that there are things that trigger the sensation of pain, but I am also convinced that the amount of suffering that a person has is related more to their perception and reaction to the pain than to the stimulus that started it off.

In a way, some patients do have to live with the pain, but it is possible to live with pain while suffering less.

Relatives and patients also want something to be done, rather than ‘nothing’ (which is how they perceive non-operative treatment). They are also subject to the overestimation of the effectiveness of common treatments. And they are inundated with stories of medical miracles and the expectation of normality provided by the medical profession, aided and abetted by the media and the medical industry.

THE NEED TO LABEL

What happens to people who do not have an identifiable disease, but still feel unwell or ‘out of sorts’? When the tests do not reveal any pathology, but they still have symptoms? They get a label, that’s what, because doctors cannot bring themselves to say: ‘Your tests are normal and you do not have any evidence of an underlying disease process. Further opinions and investigations are unlikely to help, may worry you and reinforce your illness behaviour, and may lead to unnecessary and potentially harmful treatments.’

I don’t have time for a discourse on medicalisation, but I wanted to point out that the label these people get depends on the specialty training of the doctor who sees them. To me, this means that the labels are likely to be wrong.

Most specialties have a diagnosis that can be used to label people who have vague, non-specific symptoms without clear underlying pathology. If patients complain of bloating, muscle pains, weakness, fatigue, headaches, dizziness, sore spots, chest tightness, shortness of breath, etc., the diagnosis they get will depend on who they see. The following are the diagnoses you get from various specialists.

•   gastroenterologist: irritable bowel syndrome or dyspepsia

•   gynaecologist: chronic pelvic pain or premenstrual syndrome

•   cardiologist: atypical chest pain

•   rheumatologist: fibromyalgia

•   respiratory physician: hyperventilation syndrome

•   infectious diseases: chronic (post-viral) fatigue syndrome

•   neurologist: tension headache, migraine, restless leg syndrome

•   dentist: temporomandibular joint dysfunction

•   ear, nose and throat: globus syndrome

•   allergist: multiple chemical sensitivity

•   urologist: interstitial cystitis, painful bladder syndrome

•   psychiatrist, GP: depression, anxiety disorder, somatoform disorder

•   sports physician: [INSERT NEAREST BODY PART HERE] dysfunction.

The names for these conditions change over time, and new ones get thrown into the mix. This list is not exhaustive: the psychiatrists have a lot more diagnoses at their disposal that can easily be retrofitted to any vague set of symptoms. Even the labels are vague. A syndrome just means a pattern of symptoms, and ‘dysfunction’ (my personal favourite) basically means ‘not working properly’ or ‘something is wrong’.

So, do these ‘diagnoses’ (I use the term loosely) overlap? They sure do. A study from The Lancet in 1999 found considerable overlap in the diagnostic criteria for these conditions. This is because the diagnostic criteria rely so much on subjective complaints from the patient, rather than the findings from blood tests or X-rays. Not only was there significant overlap between the diagnostic criteria, but the same kinds of patients got these conditions, and they were often treated the same way (antidepressant medication and psychological therapies). There is a more accurate label, but it is rarely used (for obvious reasons): medically unexplained symptoms.

These conditions used to be called functional somatic syndromes, but the group label changes. Central sensitivity syndromes is a recent label used to explain (and group) the syndromes listed above. Basically the theory is that these people have nervous systems that are more ‘sensitive’, so that patients are more likely to complain of pain. I think that this label is, at best, poorly supported, and at worst, simplistic, unproven and a backward step in understanding the real reasons for the existence of these syndromes (which is that they are psychological and social constructions, and are likely to be the bodily manifestations of psychosocial influences). I shouldn’t worry, it looks like that label will soon be replaced by bodily distress syndrome (I am not kidding).

A full discussion of the reasons for people to seek medical care when they are ‘out of sorts’ or unhappy with their current situation is beyond the scope of this book. The expression of dissatisfaction, unhappiness and distress through common, socially accepted and socially expected symptoms is well known, as is the validation of their condition and the release from responsibility that occurs with the provision of a label.

The reason why doctors from different fields use different labels is because they see things through their own lenses, based on their (extensive) knowledge of one particular system. They reach for the closest, most familiar labels: the ones they were taught, and the ones for which they can provide treatment. The same goes for every other alternative medicine provider.

One of the reasons why doctors label unknown conditions in the first place is that it is virtually inconceivable for doctors to say to a patient, ‘I cannot find an underlying physical cause for your pain. Be reassured that there is no evidence of any serious underlying condition that may cause you harm. There may be psychological and social reasons for your symptoms, and I would be happy to explore that with you, but I do not feel that it would be in your best interests to continue to investigate your symptoms with more tests, or refer you for any more opinions or treatments.’ Instead the patients get more tests and, worst of all, they get treatments. Injections, TENS machines, physiotherapy, hydrotherapy, opioid analgesics, spinal cord stimulators and the biggest treatment of them all, surgery. I wish it was acceptable for us to say to a patient complaining of back pain that they have a diagnosis of ‘unexplained back pain that they cannot currently cope with’, rather than a ‘ruptured disc’ or whatever other finding we lift from the MRI report (there is always something on the MRI report). The former diagnosis would be more accurate, and less harmful than the latter.

The problem is a result of the age-old disease–illness paradigm, whereby every symptom has a clearly identifiable physical cause; identify that cause and address it, and you can cure the patient. We should only be treating patients with clear, correctible pathology – those who are sick – particularly when ‘treating’ involves performing surgery. Those who have no disease but have symptoms may be made sick by medical intervention, and they should not be forced into the disease–illness paradigm. Alternative management strategies should be employed for such patients. Often, talking to the patient and reassuring them that they do not have a serious disease and are unlikely to get worse can be enough. More often it is much harder to undo the psychological and social processes that have led to the current complaints.

FINANCIAL INTERESTS

The influence of industry (one of the financial interests) over the practice of medicine has been widely covered in other books such as Bad Pharma by Ben Goldacre, The Truth About the Drug Companies by former New England Journal of Medicine Editor Marcia Angell, and many articles and books (such as Selling Sickness) by Ray Moynihan. For anyone not convinced that industry influence exists, read any one of those books.

While it is in the interests of industry to have patients treated, it is also in the interests of health workers, insurers, patients and their relatives. It appears to help no one if no treatment is provided.

Insurance companies don’t like paying out money, yet they cover so many treatments, even ones that clearly don’t work. I used to wonder why health insurers offered rebates for useless alternative medical treatments and other fringe treatments. I got the answer from an economist: insurers just want to expand their business, because every new treatment covered and every new policy gives them another opportunity to make a profit – the more they cover, the better.

What about the direct financial interests of the surgeon? This is commonly raised as a reason for surgeons to resist change and to continue operating in the face of evidence to the contrary. While I am not naïve enough to believe that surgeon decision making is not influenced in some way by financial incentives, I don’t see this as a big factor in the resistance to change. In Australia, where I live, surgeons are among the highest paid people in the country; they don’t have to do unnecessary surgery, and most of them don’t want to do unnecessary surgery. I think that a lack of awareness and a lack of understanding of the evidence, suspicion of the evidence, confirmation bias, tradition, and simply seeing people get better and assuming cause and effect have more to do with surgeon resistance to change than purely financial incentives. But maybe I am biased; after all, I make a lot of money from operating. More than I make from researching the effectiveness of surgery. Or writing books about it.

THE RELUCTANCE TO SUBJECT SURGICAL TREATMENTS TO THE PLACEBO TEST

I have provided an example in Chapter 2 on lung volume reduction surgery (LVRS), where the surgery was introduced and then, when a comparative study was suggested, it was deemed unethical to withhold surgery, which had by then become common practice. The test went ahead anyway, and surgery failed.

The LVRS example did not even involve placebo (sham) surgery, which would have been even harder to sell. The cries of ‘unethical’ for surgical trials is partly due to confusion between the ethics of clinical practice and the ethics of scientific research. This was touched on earlier, but is explored in more detail in ‘Ethical double standards’, below (see page 224).

Apart from ethical objections, one of the reasons for objecting to sham surgery trials is a lack of understanding of their underlying nature – of the scientific power that such trials hold in overcoming bias and providing us with a better estimate of the true effectiveness of a procedure. This lack of understanding is revealed regularly in debates, meetings and writings about evidence-based medicine. One example is from a journal editorial commenting on the sham surgery studies of knee arthroscopy, in which the author suggests that patients who agree to participate in sham trials are not of sound mind, and that the results are therefore not generalisable to ‘mentally healthy patients’. The name of the journal? Arthroscopy.

THE ‘WOBBLY TRIPOD’ OF SURGICAL EVIDENCE

If surgeons think that placebo controlled trials, or any type of randomised trial, are rarely necessary, on what do they base their clinical decisions? Mostly, their decision making is based on the ‘wobbly tripod’ of surgical evidence. There are three arms (legs?) to the tripod, and it is wobbly because each leg is weak, and often collapses under the weight of stronger evidence. The three legs of the tripod are:

1   The biologically plausible mechanism: Biological plausibility is a requirement for any treatment, but it does not supply its own proof of causality; it merely provides a possible explanation (which may direct future research). Therefore, it is more important in its absence than its presence. The problem I have with the biological mechanism is not (usually) related to the mechanism itself – the problem is that people tend to take a biologically plausible mechanism as evidence of effectiveness, and that it ain’t.

2   Related evidence from laboratory and animal studies: Part of the problem with this is the presumed accuracy of such data. There is an assumption that experiments from a laboratory are free from the biases often associated with clinical studies; that they are somehow more precise. Anyone who has done these sorts of studies knows that this is not the case. Also, they are a surrogate outcome for what we’re really interested in (the problems with using surrogate outcomes could be the subject of another book) and for lab studies, the differences between the testing environment and the complexities of real life are large. When people talk about getting the findings of lab studies into clinical use, they use the phrase ‘bench to bedside’, but in my experience the path from ‘bench’ to ‘bedside’ is a long and difficult journey that is rarely completed.

3   Personal observation: Assigning cause-and-effect to an observed association has driven human decision making since there were humans. It is a very strong driver of behaviour and is probably the main reason why we have difficulty changing a practice that already fits our world view. The problem with personal observation is that it is unreliable: it is highly susceptible to bias, yet we seem to trust it greatly.

Critics of placebo surgery studies tend to underestimate the societal and future benefits that can result from showing a surgical procedure to be ineffective. There is concern about the risks of placebo surgery in trial subjects but, ethically, the risks of the sham surgery need to be weighed against the potential benefits of the research. There needs to be greater consideration given to the harmful effects of real but ineffective operations that continue to be performed, and to the potential financial and health benefits of removing such procedures. And if the placebo study shows the surgery to be effective, then great: you now have the evidence you need to justify using this procedure, and it would be hard for funders to argue with you.

The need for placebo-controlled trials in surgery is great. Many state that in order to demonstrate the effectiveness of a surgical procedure, you only need to compare it to any non-operative therapy (not a placebo), because this will demonstrate any net therapeutic benefit of surgery. However, this net therapeutic advantage may be due to the placebo effect of surgery. It is not a good measure of the specific (true) therapeutic effect of the intervention, only the perceived therapeutic effect.

I am not suggesting that placebo surgery trials are necessary for all procedures. It depends on many factors but, basically, you need placebo surgery when you expect a placebo effect. For example, you don’t need a placebo surgery trial for ‘hard’ objective outcomes like death, because the placebo effect is unlikely to affect one’s risk of dying. You do, however, need a placebo trial when the outcomes are ‘soft’ (subjective outcomes, like pain). Tests of surgical procedures for back pain, knee pain, headaches, neuralgia, tennis elbow, etc., cannot properly adjust for the placebo effect of surgery unless they are compared to placebo surgery.

THE IMPORTANCE OF PLACEBO SURGERY TRIALS

Whether or not it is on ethical grounds, there is a reluctance to perform placebo controlled trials in surgery. Let me illustrate the importance of doing so with an example.

Currently, every year more than one spine fusion is being performed in the United States for every thousand people living there. Many of these fusions are being done for pain and for degenerative conditions.

A well-conducted placebo trial of spine fusion surgery can be done ethically, but would need to recruit several hundred patients. For the sake of argument, and to allow for multiple trials, let’s say 1000 people are recruited, 500 of whom will have placebo surgery.

One possible outcome of the trial is that the procedure is shown to be effective. If so, the placebo group will be disadvantaged, but will be allowed to have the procedure performed at the end of the study if their symptoms are still present. The benefit of this outcome is that we can treat future patients using spine fusion surgery with more confidence.

The other possible outcome is that the procedure is no more effective than placebo (a plausible outcome, based on current evidence). In this case, the cost and complications of millions of future operations would be avoided. The benefits to society and to patients would be enormous. If such a trial had been done thirty years ago, even more costs and complications might have been avoided.

ETHICAL DOUBLE STANDARDS

The current ethical environment is one that holds back research into the effectiveness of surgical treatments, but does little to reduce the rate of ineffective treatments currently performed. Ethics committees (institutional review boards: IRBs in the US) are now firmly entrenched in the research environment such that clinical research can only be performed with their approval. Clinical practice, however, is not subject to such approval, yet in many cases the risk of harm (individually and to society) from clinical practice is greater. Therefore, researchers are being held to a higher standard than clinicians, and our focus on ethical standards for clinical research has led to an ethical blind spot for clinical practice.

Rightly, ethics committees have considerable control over research. Their role is to minimise the risk of harm from clinical research. Examples of such harms exist, and these examples (including World War II atrocities) led to the development of ethical standards for research. However, the committees only have control over what is submitted to them, and they tend not to concern themselves with clinical practice at their institution. The requirement for drugs to be approved prior to clinical use is that they need to be shown to be safe and at least equivalent to current treatments. For implants and devices, the requirements are lower: placebo trials are not necessary, nor are large-scale comparative trials. Mostly, devices only require theoretical and laboratory support to show that they perform as intended. For techniques that do not involve devices or drugs, like new surgical techniques, you just need to try it out a few times, and there is no requirement for oversight or reporting.

For research, however, the standards are different. For example, if you’re doing a procedure that has not been subjected to a trial, or if there are practice variations with an intervention, ethics committee approval is not required to perform the procedure, but such approval is required to measure the outcomes (if any patient contact is required and publication is expected). Let me rephrase that: there are no ethical restrictions on what type of procedure you perform, but if you want to measure the results of that procedure, you need approval.

Rather than researchers asking for ethics approval to follow up patients, shouldn’t it be the other way around? Shouldn’t those in charge of ethical standards be demanding that we measure our outcomes? To me, not measuring the outcomes is unethical. And shouldn’t those in charge of ethical standards for an institution cover all clinical activity, not just research?

In fact, I would argue the exact opposite of the current situation should be the case: that ethical approval should be required before performing a new procedure, and that it should not be required to measure and report the outcome of that procedure.

As mentioned earlier, there is a difference between the ethics of research and the ethics of clinical practice, but it does not explain the double standard. In fact, the ethical standards for clinical practice are stricter than those for research, yet it is clinical practice that is not covered by ethics committees. For clinical practice, the guiding principle covering new or untested techniques is to ‘do no harm’. In other words, if you aren’t sure about the treatment, don’t go there. The ethics for research says: if you aren’t sure about the treatment, go there: do the research and measure the outcomes. The ethics for research does not say to ‘do no harm’, but to ‘balance the (individual) harms against any (societal) benefits’.

This might be better explained with a real-life example. A new surgical approach to hip replacement surgery has recently become popular. The ‘approach’ refers to how the surgeon gains access to the joint – where the incisions are placed and what muscles they go between or through. A direct anterior approach is considered to involve less cutting and damage to other tissues, but it is difficult, and there is a learning curve. Many surgeons do not do it, but many have tried it, and some use it commonly.

If a surgeon wanted to do a study comparing the direct anterior approach to the standard approach and to publish the research, the surgeon would need the approval of an ethics committee in order to ensure that the research satisfied the criteria for privacy, safety, consent, etc. This is very hard to do, so most surgeons don’t do such studies or report their outcomes using this approach.

What happens instead is that the surgeon simply starts using the new approach, often after appropriate training, but without reporting the results of the surgery. There is no restriction on what surgical approach a surgeon uses to do an operation, so what we have is a situation where it is deemed unethical to find out the results of a new procedure and publish them (without prior approval), but it is deemed ethical to do the procedure and not report the results.

What should happen is that clinicians should not be performing any treatments until they have been tested. What is happening is that clinicians are performing many treatments that have not been adequately tested, and researchers are being hampered from evaluating those treatments.

One of the concerns is that if we raise the barriers to clinical practice, we might delay the introduction of beneficial treatments. This is true; however, what often happens is the opposite: treatments become entrenched, so that it then becomes ‘unethical’ to do a controlled trial. This is how we end up with the current problem of overtreatment due to ineffective and harmful procedures. I would rather have a few delays than the mess we have now, with so many procedures being performed without good supporting evidence.

The ethical hurdle for research is higher than for clinical practice. To correct this, we need to lower the ethical requirements for clinical research (particularly for things like patient follow-up and surveys), and raise the ethical requirements for clinical practice. Otherwise, we have the current situation, where telemarketers can call my patients whenever they want and ask them anything, but I can’t even call them to find out how they’re going, if I call it research.

BIAS IN THE SCIENCE

When surgeons attempt to base their practice on the available science, they can still come up with the wrong answer. This is because scientific studies vary in their quality. High-quality studies (which have a lower risk of bias) provide us with a better estimate of the true effect, but the lower-quality studies are not only further from the truth, they tend to be further from the truth in one particular direction (in other words, they are biased). The direction in which they are biased is towards the treatment being effective. So when there are only low-quality studies, we often come up with the wrong answer.

But even the high-quality studies are not that good, or are misleading. In surgical trials, our unit has reported on the quality of randomised trials and systematic reviews, which are supposedly at the top of the quality pyramid. We chose a random sample of surgical randomised trials and found that the scientific quality was less than perfect. Less than half of the studies reported the method of randomisation, whether randomisation was concealed, what the primary outcome was, or even calculated how many patients they needed. Only 37 per cent attempted any form of blinding (while it is difficult to blind the surgeons and patients, it is usually not so hard to blind the people assessing the outcome).

There is empirical evidence that skipping some of these important steps will lead to bias in the results. The other problem with not specifying things upfront in such trials is that it leaves the door open to ‘flexibility’ in the interpretation of the findings. In another review of surgical randomised trials, we found that many of the outcomes that were measured were not reported. This is not just ‘incompleteness’, it is bias – we showed that of the many outcomes in each study, those that were statistically significant were much more likely to be fully reported.

We also looked at studies that summarised the trials in a particular area – so called ‘systematic reviews’. We found that the surgical systematic reviews, on average, provided evidence of compliance with less than half of the criteria for a widely accepted quality standard.

The upshot of the poor methods in surgical studies is that anyone who calculates the effectiveness of surgery using published studies is getting biased information that is likely to make surgery appear more effective than it really is.

There are other problems with the research that is presented. Take comparative effectiveness studies as an example. We often jump to the wrong conclusion when we read studies comparing treatment A to treatment B. When studies compare a treatment to nothing, or to a placebo, it is easy to understand the results. Studies that compare two different treatments are harder to interpret. They will either show one treatment to be superior (say, treatment A over treatment B), or that there is no (significant) difference between them. But what does that mean?

In the first case, where treatment A is superior, we conclude that people should use treatment A, because it is better than treatment B. We do not consider the possibility that both treatments are bad, possibly even worse than doing nothing, or worse than some other treatment. Even if both treatments are harmful, but treatment B is more harmful than treatment A, we would still get the same results (that is, that treatment A is ‘better’ than treatment B). The example I will use for this presumed effectiveness involves spinal cord stimulators for back pain.

Spinal cord stimulators are devices implanted in the spine and are commonly used for chronic back-related pain. Despite some risks, widespread use and high costs, these devices have never been compared to placebo. One study, however, compared the device to repeat spine surgery in patients who had continued or recurrent leg pain after spine surgery. The study concluded that the spinal cord stimulator worked better than repeat surgery.

The interpretation of this study, for most people, is that spinal cord stimulators make people better. However, repeat spine surgery for failed back surgery is notoriously unreliable and can often be ineffective or make people worse. There is an old saying that if the first operation didn’t work, operating a second time is unlikely to help, and a third operation will only make things worse.

The study does not tell us that the spinal cord stimulator had a direct effect on the patients (beyond any placebo effect), and it is also possible that the stimulator is simply ‘less harmful’ than repeat surgery.

In the second case, where both treatments are similar, we assume that they are equally effective, and that we can treat patients with either of these two treatments. We do not consider the possibility that both treatments are equally ineffective, or even equally harmful. The example I use for this is a recent article that compared two treatments for leg pain from sciatica (due to a pinched nerve in the back).

The study, which was blinded, randomised and used sham treatments, showed that gabapentin, a new and very popular drug for ‘nerve pain’, was just as effective as epidural steroid injections. The conclusion was that both treatments were effective. However, given that high-quality studies of epidural steroid injections show little or no meaningful or lasting benefit over placebo, the possibility that both treatments are equally ineffective should be seriously considered. As for gabapentin, it had never been tested against placebo for sciatica. Surely that study should have been done first. We have now done that study, but the results will not be published until after the release of this book. (I have included a reference to the protocol in the references for this chapter, so the study can easily be found once it is published.)

You can see how comparative studies can be misleading or, more likely, how they can be misinterpreted.

The persistence of ineffective or unproven (possibly ineffective) surgical treatments is driven by our human nature (our inherent biases and our wish to believe), the converging interests of all the players, and also the simple fact that it is often easier to go with the flow. The persistence is also driven by the bias that exists within society that medicine is, unless proven otherwise, beneficial. New treatments are introduced on this basis, and unseating them is difficult for the same reason. Even relying on the scientific evidence means relying on something that is inherently biased. There needs to be more acceptance of a doctor who says ‘I’m not sure that you’ll be better with surgery, so it would be better if we avoided it.’ A doctor should be able to say that without being accused of neglect, incompetence or a lack of bravery.

8

SURGERY HAS A PLACEBO EFFECT – SO WHAT?

THE CASE AGAINST USING THE PLACEBO EFFECT

WHY EXPOSE THE myth, particularly when everyone benefits from it (patients, surgeons, hospitals, insurers)? Believe it or not, this is a commonly used argument: if people are getting better after surgery anyway, that’s great – the fact that the placebo group also got better is no reason to stop doing the surgery. I have even had surgeons tell me that the sham studies on arthroscopy (that show no difference between surgery and placebo) are great news because they show how ‘effective’ surgery is, in that so many patients get better afterwards, and it means that we should be doing more arthroscopic surgery, not less.

These surgeons are basically saying that we should harvest the placebo effect to the patient’s advantage (and, coincidentally, theirs). Well, apart from being a misrepresentation of the term ‘effective’, this kind of thinking highlights a problem (which I am guilty of perpetuating) regarding the use of the term ‘placebo effect’. This is covered in Chapter 1, but I think I need to clarify this problem further.

I have three specific objections to surgeons performing surgery that is no more effective than placebo, despite how ‘effective’ the surgery may seem. I have listed those objections below, but my main, overall objection is that despite what I have told you, there is no placebo effect. The very definition of a placebo excludes any effect. I have used the term ‘placebo effect’ to explain some of the improvements in patients that occur after treatment; however, much of that improvement is not really due to any direct effect of the placebo, but due to more mundane things. For example, many conditions improve anyway (like the common cold) and many tend to fluctuate in severity, like osteoarthritis, migraine and multiple sclerosis. If, for example, we performed an arthroscopy on a patient with osteoarthritis of the knee every time the symptoms were at their worst, the surgery would appear to work every time because after every severe exacerbation of osteoarthritis is a period of relatively lower symptom severity: an improvement.

I have already discussed the reasons for improvement that we often attribute to the placebo effect; things like natural history, regression to the mean, concomitant treatments and bad (biased) science (distorted measurements and definitions that make treatments appear effective). If a surgeon is relying on these things to ‘harvest’ the placebo effect, they are not really making the patient better: they are either amusing the patient while their condition improves, or deceiving them. Or both.

But even accounting for all of those reasons why a condition may improve after treatment, sometimes there is still some perceived improvement – what’s wrong with playing on that? Well, firstly, if the perception of improvement is on the part of the doctor, it is not doing the patient much good. If it is the patient’s perception of improvement, then I can see a point in the argument, but I find that such improvement, if present at all, is often mild and short-lived. And again, this perceived improvement is not really the effect of the placebo – it is a product of the therapeutic envelope: how the placebo is dressed. Anyone in advertising knows how placebos work: it is not the product, it is the presentation. And anyone in advertising or politics knows about the importance of perception over reality.

For surgeons playing on the placebo effect, it is a case of using the operating theatre as a theatre was originally intended: as a place of illusion. Surgeons need to decide if they are scientists or marketers; whether they deal in facts or fictions; and whether they are true healers or faith healers.

Regarding the validity of using placebos, there has been some interesting research on the use of ‘open label’ placebos, showing that they can provide some perceived benefit based on adjusting patient expectations and other psychological factors. However, although patients are told the treatment is a placebo, they are usually told that ‘this treatment has been shown to be effective in some patients’, so the problem remains, because you are still telling them that the placebo is effective. The only difference is that you are using the word ‘placebo’ out loud; it still works because the patients believe (and expect) that the treatment is effective (possibly through a misunderstanding of what the doctor is saying, because deep down patients believe that doctors do things that help them – that is their default position).

If you are thinking that this is just a hypothetical argument, you are wrong. Many doctors deliberately provide treatments that they know to be ineffective, just for their placebo effect (not just to get the patient out the door). In a survey of general practitioners in the UK, it was shown that most (77 per cent) use placebos on a weekly basis.

WHERE’S THE HARM?

But even if we accept that there is a placebo effect from surgery (outside of the perceived effect resulting from improvements that would have occurred anyway), I still have objections to placebo treatment being used. There are three main problems with the attitude of ‘Where’s the harm from capitalising on the placebo effect? Everybody else is doing it.’

Objection number 1: it’s unscientific

Using a placebo to treat someone is to say something is effective when it is not. This is not truthful, and this makes it unscientific, and it puts us in the same league as non-science-based medicine.

Using a placebo involves deceit at some level. It means that doctors are either deceiving the patients (when they knowingly give patients a placebo), or that the doctors are deceiving themselves. Even though many doctors admit to using the placebo effect, I believe that they are more commonly deceiving themselves by doing what they have been taught without challenge, and by not taking a sceptical (scientific) approach to treatments. This attitude often pays better, and it is also easier, particularly if everybody else is doing the same thing.

The ‘unscientific’ aspect of using the placebo effect is interesting. It can lead to a situation where a doctor will admit to using the placebo effect to treat patients, yet that same doctor will criticise the use of alternative medicine on the grounds that alternative medicine is not scientific. The difference between alternative medicine and mainstream medicine is that mainstream medicine is based on scientific principles. However, too often those scientific principles are not followed in mainstream medicine.

When an ‘alternative’ medical treatment is proven to be effective in a rigorous scientific test, it is no longer ‘alternative’ and may then be used by mainstream medicine. It is a shame that the opposite is not true – that when mainstream medical treatment are not tested, or are tested and shown to be no better than placebo, they are not relegated to the status of alternative medicine. Doctors like to hang on to their treatments, especially when they are perceived as being effective, and as long as people keep paying for them.

In short, to use a placebo to treat patients in mainstream medicine is to remove the barrier between mainstream and alternative medicine. It uses deceit by falsely attributing effectiveness and by raising expectations. It is the craft of the faith healer, the homeopath and the magician, not the surgeon scientist.

Objection number 2: the cost

There are two costs to consider when using the placebo effect to treat people: the direct financial cost and the opportunity cost.

The financial cost is not confined to the cost of the pill or the procedure, and we should look beyond the number of dollars that the patient parted with. Most treatments involve costs for government and insurers, who often contribute to treatment costs. There are also costs of transport, costs imposed on carers, and loss of income from time off work.

We tend not to look behind the superficial, visible costs of treatment. It is common in my country, for example, to say that surgical treatment in public hospitals is ‘free’. An economist will tell you that nothing is free. We are all paying for it, if not directly, then through insurance premiums and state and federal taxes.

For a placebo pill, the direct financial cost might not add up to much. For antibiotics, the costs might be a little higher. For surgery, however, we are looking at big costs, no matter how you add it up. Surgery usually involves all of the possible costs for patients, carers and society (insurers, employers and government): things like consulting fees, investigations, hospital fees, theatre costs, implant costs, affiliated treatments (like rehabilitation), time off work and carer costs.

Opportunity cost refers to the opportunity lost by committing to the placebo treatment. In simple terms, how much (truly) effective treatment could have been provided if we didn’t waste time and money on the placebo surgery? Like direct financial cost, opportunity cost impacts not only on the patient, but on carers and on society. It is particularly relevant for insurers and governments, who are faced with escalating medical costs and increasing demand for medical services. Medical services compete with each other for funding, but they also compete for funding with education, welfare and law and order.

For those responsible for working out how to best allocate the money, my suggestion is that placebo surgery is not a good investment.

Objection number 3: the harm caused

Lastly, if our operations are not having a direct benefit, they are certainly causing a direct harm.

The global volume of major surgery in 2004 was approximately 250 million cases per year – about one operation for every twenty-five people in the world for that year. In developed countries, major morbidity (any harmful outcome) complicates 3–16 per cent of all inpatient surgical procedures, with permanent disability and death in 0.4–0.8 per cent, and with half of the adverse events being identified as being preventable.

Surgical procedures rank high as a proportion of overall medical harm. Large-scale studies have estimated that up to 16 per cent of all hospital admissions had an adverse event; over half of these were associated with surgery, and nearly half were considered preventable. This equated to 18 000 deaths per year (in 1992) in Australia.

In the US, 250 000 deaths per year due to medical harm would make this the third leading cause of death. Others have estimated it at closer to 800 000 (and therefore the leading cause of death), and others as low as 44 000. But while the numbers vary, it is likely that these figures underestimate the true harm, as the medical data usually only encompasses in-hospital data (not counting harm in primary care and outpatient settings), and the American College of Surgeons has stated that only 5 to 30 per cent of the surgical incidents are reported.

A 2010 report from the Department of Health and Human Services Office of Inspector General (US) estimated that 27 per cent of Medicare patients are harmed from medical care in hospitals, costing $4.4 billion per year, and that half of the harms were preventable. They also estimated that 180 000 deaths per year occur in Medicare patients as a result of adverse events. Specific to surgery, it has been estimated that there are 12 000 deaths per year in the US due to unnecessary surgery.

These figures for medical harm tend to be challenged, rather than investigated further. Whatever the real number of deaths from adverse events or unnecessary surgery, and whatever the true proportion of avoidable harms might be, it ain’t zero, and it is likely to be considerably higher than many would think.

WHAT ABOUT WHEN WE JUST DON’T KNOW?

When a surgical procedure has not been subjected to rigorous evaluation, we have to make a decision on whether or not the surgery is effective. We can do that either by assessing the evidence that is available (usually from case series that have been reported, that do not have a comparator, let alone a placebo) or by generating new evidence (doing a high-quality study to answer the question of effectiveness). Just seeing patients get better is not enough, as, without a comparative study, we can’t know whether they would have got better anyway.

As you have seen before, there are many examples of surgical procedures that were thought to be effective based on observation alone (a surgeon’s own observation, and case series, which report the observations of others) only to later be shown to be ineffective under more rigorous testing. What I have not covered to this point is the operations that were thought to be effective based on observational evidence, but were later shown in comparative trials to be much less effective (rather than completely ineffective). This commonly occurs, and it makes me wonder how truly effective many of our treatments are if they have not been subjected to high-quality comparative trials. I use cancer surgery as an example of surgery that has some effect, but where the size of that effect is shown to be much less than we thought when it is studied objectively.

Cancer surgery

Prostate cancer and breast cancer are common in men and women, respectively, and are both commonly treated with surgery.

Looking at the survival of patients with prostate cancer who undergo prostatectomy, the results look good. Observational studies (reports of series of patients who have undergone prostatectomy) tell us that the prostate cancer-free survival is about 80 per cent after 20 years. The complication rate of surgery is high, but the urologists tell me that the complication rate and severity are better now than in the past. Based on this type of evidence, and if I were a urologist observing patients after prostatectomy, I would consider it to be a very effective operation. If I were a patient, I would think that the risks were far outweighed by the benefits.

The problem is that when we look at one-sided evidence (the results of a procedure with no comparator or control group), we tend to compare it to a worst-case scenario. If the survival is high after surgery for cancer, we tend to think that without surgery, things would have been worse – possibly fatal. The ‘take-home’ message from the statistic I provided above is that the surgery is 80 per cent effective at saving lives or curing the cancer.

When compared to not performing a prostatectomy, the survival benefit is not that clear. In one highquality randomised trial of prostatectomy versus non-operative treatment, the ten-year mortality was 47 per cent in the surgical group, compared to 50 per cent in the non-operative group (a difference that was not statistically significant). Note that this is overall (all-cause) mortality – a more important outcome than disease-specific mortality. Complications such as erectile dysfunction and urinary incontinence were two to three times higher in the surgical group. This study only included men who were likely to benefit from surgery (localised disease, expected to live ten years, under 75 years of age). A 3 per cent improvement in survival over ten years is likely to be less than patients would expect. When weighed against the high rate of complications, the decision to have surgery is not always a simple one. Now consider more questionable cases in patients over 75 – common candidates for surgery. Is there any survival benefit to surgery, and, if present, does it outweigh the possible loss in quality of life?

For breast cancer, the most common tumour detected on mammography is DCIS (ductal carcinoma in situ, a low-grade cancer). This is treated with surgery, after which the chance of dying of breast cancer over the next twenty years is about 3 per cent. Most women who have had this will think that the surgery has cured them of breast cancer, which it probably has, but what would the chance of dying from breast cancer be without treatment? In the study, there was no difference in the mortality between treatments (mastectomy versus lumpectomy); mastectomy only reduced the local recurrence, not the chance of dying from breast cancer. What happens to DCIS when left alone? Many cancers can remit, and studies of breast cancer screening are less than convincing. Most cases of DCIS are detected by screening, and DCIS makes up about one third of all breast cancers detected by screening, yet a recent study from Canada shows us that the risk of dying from breast cancer over twenty-five years is not reduced by screening, despite the fact that many more of these low-grade tumours are detected. Prior to this, the Cochrane review on mammography screening, which included data from trials including over 500 000 patients, concluded that in the trials with adequate randomisation (between screening and no screening) screening did not significantly reduce the all-cause mortality or the deaths from breast cancer over ten years, despite the screened patients having a lot more cancers detected and undergoing a lot more treatment.

Whatever the difference in mortality may be, the 97 per cent of women treated for DCIS who do not go on to die of breast cancer are likely to attribute their survival to surgery – yet many would never have known they had cancer without screening, and would not have died from that cancer in any case.

I am not saying that we should not do the surgery, only that the effectiveness is overestimated. And whether we call it placebo or not, many patients having cancer treatment have perceived their surgery to be effective in curing them when it may not have influenced the outcome. And doctors are taking the credit.

Using the placebo effect of surgery to treat people and overselling the effectiveness of surgery is not medicine as I understand it. It is not scientific or transparent. It is potentially deceitful, harmful and wasteful of resources.

9

WHAT CAN WE DO ABOUT IT?

AS PATIENTS, DOCTORS, RESEARCHERS, FUNDERS AND AS A SOCIETY

IN GENERAL, we all need to be a bit more scientific with our approach to decision making. Daniel Kahneman wrote in Thinking Fast and Slow about how our initial, intuitive, human, short-cut fast thinking, which is often good for making safe decisions about survival in the wild, can often let us down; it is our more rational, scientific, slow thinking that gets to the truth of the matter.

We need more slow thinking about medicine, but in order to do that, we need to be aware of the biases in our initial responses: our tendencies to attribute cause and effect to associations, and to look at medicine through rose-coloured glasses.

We also need to recognise biases in research that tend to overestimate benefits and underestimate harms.

In essence, we need to be sceptical, not gullible. Being sceptical means being rational and scientific – which is different to being cynical. We need to stop accepting things on face value and to question the reasons behind the decision to perform a surgical procedure, and not to accept tradition, observational evidence or experience as proof of effectiveness.

There are, however, specific things that you can do, depending on your role on the surgical stage.

WHAT CAN PATIENTS DO?

Many patients look things up themselves, usually on the internet. This is fine, as long as they know where to look and have the tools to appraise the evidence that they find. For some, especially those with good common sense and some scientific training, this can be fruitful and revealing, but not everyone can do that.

The rest will need to get good advice. You can get good advice from your treating doctor by asking the right questions. The best question is to ask about the difference between the results of any proposed surgery compared to the best non-operative alternative. And when I say ‘results’, I mean whatever it is that you want to get out of the operation. If it is survival, simply ask Am I less likely to be dead in five years if I have surgery, compared to not having the operation?’ If it is more complicated, like trading off pain relief and possible complications, just ask for the numbers, like ‘Am I more likely to have less pain with surgery, and what is the likelihood of each possible complication from surgery?’

If you can’t get good advice from your treating doctor, see another one. In fact, if there is any doubt at all, see another one anyway. See two other ones. There are plenty of doctors around and, despite what many people think, surgeons generally don’t mind their patients getting second opinions or going elsewhere for treatment. Surgeons know that second opinions can be helpful for them and for the patient. If the other opinions are the same as that of your first doctor, it makes you and your surgeon feel better about proceeding. If there are differing opinions about whether or not you should have surgery, then you have a decision to make, but make it based on the probabilities of benefit and harm, not on the charisma of the surgeon, on the degree of technology involved, or on the glossiness of the brochure. And certainly don’t make a decision based on the assumption that doing something is better than doing nothing.

For patients, I believe that the more relevant information that they have, the happier they will be with their decision. Also, the more input the patient has in the decision making process (so-called SDM: shared decision making), the happier they will be with the result, particularly if the result is bad. A patient will be less likely to blame someone else for an undesirable result if they themselves made the decision to have the procedure (providing they had all the relevant information). What is interesting, though, is that studies have shown that when patients have more information and more involvement, not only are they happier with their decisions, but they are also less likely to choose surgery.

Another thing that patients and the public in general can do is to be part of the solution. Health care consumers are well-placed to guide research activities, and their involvement in all aspects of research is being increasingly recognised as both important and beneficial. Members of the public have long been members of research ethics committees that oversee research activities, but consumers can now be involved in setting the research agenda by determining the priority areas for future research. They can assist in choosing what outcome measures are important and how they should be collected to maximise the relevance and rigour of the research. They can also be involved in the conduct of research (even as investigators and authors), the reporting of research and the ultimate dissemination and uptake of research findings. Such involvement will increase the relevance of research to the recipients of health care and also increase the likelihood of the research changing medical practice for the better.

WHAT CAN DOCTORS DO?

Doctors need to follow the general advice above, about being more scientific and questioning. They can do this by practicing what is referred to as evidence-based medicine, which I prefer to call science-based medicine. This means that they need to use the least biased evidence available to them when making decisions about individual patients, not the evidence that best fits with their beliefs and their practice to date. Basically, doctors need to apply the questioning attitude they have towards other surgeons, physicians and other health and alternative medicine practitioners to themselves and their own practice.

For many doctors, this is a big ask. With so much evidence out there, it is hard to evaluate every decision so carefully. Many do not know how to scientifically evaluate the evidence. Firstly, they should obtain that knowledge by learning about evidence-based medicine and the scientific principles of critically appraising the available evidence. Secondly, the best available evidence is often summarised for them. There are many high-quality practice guidelines and summaries available for most common conditions and their treatment, including surgery.

This questioning attitude is particularly difficult to put into practice for trainee surgeons – junior doctors who want to be promoted and advance their position. Often they are reluctant to challenge a superior. I know many trainee surgeons who know when their supervisor is doing unnecessary surgery, but they rarely speak up. I am occasionally challenged by those working under me. Initially I found this uncomfortable; now, I love it. I love that they feel that they can do this, that they have the confidence to do it, and the knowledge that feeds that confidence. I can give many examples of how my practice has changed (for the better) due to my being challenged by a junior. I believe that if such interactions between surgeons are based on the science, and if the culture becomes more accepting and understanding of science, it will be easier for surgeons to question each other, regardless of their relative position.

Beyond using the available evidence, doctors should be generating new, better evidence. They should design, conduct or at least participate in clinical trials and other types of research aimed at answering important clinical questions about the effectiveness of surgical procedures. Not only will this better answer the questions, but personal involvement in research makes one more likely to believe the outcome.

Many surgeons participate in research, but often it is research that does not address important clinical questions, or research that cannot properly answer the question it is addressing. There is considerable waste in medical research (not just surgery), and better focus is required.

Doctors also need to remove any financial incentives from their decision making. Financial structures that reward procedures rather than overall care tend to lead to higher rates of surgery. Financial interests in devices and device companies, through such things as royalties, speaker fees and education payments, can influence the decision making of surgeons. Currently, the system around declaration of such conflicts is robust – but declaration of a conflict does not remove it.

Surgeons also need to talk to one another: isolated practitioners with little access to peer review tend to go off on a tangent. Having surgeons regularly meet in groups to discuss cases decreases practice variation. Attending meetings might seem like a waste of time, and peer review has been criticised (for example, when everyone in the group agrees on the wrong thing), but at least it is a leveller.

But it’s not all about the surgeons; the primary care doctors – the general practitioners – need to think twice before referring patients to surgeons. They need to be aware of the adage that ‘to a man with a hammer, everything looks like a nail’. Surgeons operate – it is what they do.

Given that medical students are mainly taught by doctors, there is considerable room for improvement in medical education. I learned very little of the scientific method in medical school, and almost nothing about how to critically appraise the research, or about bias. We need to create scientists who practice medicine, not doctors who know about medicine but little about the science that supports it.

Finally, professional societies can do a lot to improve medical practice. I believe that there is a greater role for professional societies in monitoring and improving the quality and safety of surgery. Many have done this, but many have not embraced this role, confining themselves to codes of conduct, specialist training and ongoing education rather than enforcing adherence to evidence-based guidelines, producing those guidelines and producing new evidence through research.

As a result of the increased awareness of medical harms (mentioned in the previous chapter), considerable work has been done to address error in surgery. This has resulted in a better culture of safety, and has involved changes such as the introduction of surgical checklists. These checklists are used immediately prior to the surgery to ensure that the right procedure is being performed, on the correct side and on the correct patient, among other things. I think that system changes that reduce error are important, but they also distract us from the important questions around surgery – the ones that are not on the checklist. Questions like ‘Is this surgery necessary?’ or ‘Are the results of this procedure clearly better than nonoperative treatment?’ But of course we should be asking that question a little earlier in the game.

A recent project, called Choosing Wisely, has been successful in getting professional societies engaged in disinvesting from low-value interventions. Professional societies were asked to generate lists of five interventions that should be questioned, and the response was very positive. Some of the recommendations are helpful to patients, like avoiding bed rest for back pain, not using testosterone for erectile dysfunction, and avoiding opioid medication where appropriate. In my opinion, however, they fall short: the surgical societies are not strong on questioning surgery. The American College of Surgeons list of five interventions mentions only one operation – the rest were investigations like X-rays, CT scans and screening tests. The list from the American Academy of Surgeons does not refer to any operations, mainly listing ineffective non-surgical procedures. A fellow researcher has commented that the Choosing Wisely campaign has been used by specialist societies as an opportunity to cast the spotlight of ineffectiveness onto other specialities.

WHAT CAN RESEARCHERS DO?

Not every researcher has sufficient knowledge of basic scientific principles, like bias and how it occurs, and how it can be detected. Without a good grounding in this part of the scientific method, researchers will make errors unknowingly.

At a simple level, researchers should attempt to be more objective and realise their own biases in favour of their treatments. As Richard Feynman, the great scientist, explained, researchers should be looking for reasons why their favourable findings are wrong, not glossing over or dismissing negative findings. They should be trying to disprove themselves, and when they find that they cannot, then their findings will be much more robust than if they spent their time looking for ways to make the research look good.

There are other, more practical measures that researchers can take. There is now a well established practice of ‘registering’ trials before conducting them. This not only allows people to find trials, particularly ones that did not make it to publication, but it forces the researchers to put all their cards on the table before starting the research. Often the study protocols are published in journals prior to research projects commencing, thus avoiding the temptation for the researcher to change things along the way, or to selectively report the favourable findings.

Regarding reporting, there are now well recognised standards for reporting clinical trials that have helped improve the quality of research. Those standards are not always met, of course, and the plethora of new journals built on a user-pays business model have not necessarily helped raise the standards (see the section on ‘predatory’ journals, below).

Journals themselves need to be better gatekeepers. I am a reviewer/editor for several journals, so I know that the peer review system is less than perfect. This is common knowledge and not even debated. The problem is that there are only so many people who want to do that kind of work for free and who have the skills to do it well. I will be the first to say that my reviews are often less than perfect, usually because I spend less time on them than I should. Having said that, I have had many interactions with journals over the years (as both a reviewer and an author) where I have been impressed with the efforts of the editors in improving the quality of individual manuscripts.

Several of the major journals have been behind the drive towards better evidence-based care by demanding better quality trials, and through initiatives such as the British Medical Journal’s ‘Too much medicine’ series.

‘Predatory’ science

Science progresses because it is open to scrutiny. For findings to be accepted, they must pass peer review and must be presented to other scientists for them to question, refute or confirm. Publication in scientific journals (and presentation at conferences) is key to this process. However, the number of journals and conferences have increased massively over the last ten to twenty years, and many of them are not the real thing – so called ‘predatory’ journals and conferences have sprung up. The problem with this (apart from the promotion of bad science – the lowering of standards) is that there is no clear line between what is real and what is fake.

Whatever claim you make in the world of science, you will not be taken seriously until you have your work peer reviewed and accepted for publication in a scientific journal; this is how things go on the record. The process is that your study is subjected to scrutiny (peer review) and then put in an uneditable format for anyone in the world to read and challenge (or support).

A lot of work goes into preparing a manuscript for publication, and a lot of work goes into reviewing and editing manuscripts before they are published. The reputations of the authors, reviewers, editors and the journal are at stake. Traditionally, process limitations and (paper) page limits meant competition for space, which drove up the quality.

But now we have online publishing: cheap, fast, accessible and with no page limits.

Many traditional print journals are now available online, and there are some journals that are online only, which are usually ‘open access’ (no subscription fees). But open access means that the money has to come from somewhere, and this is where the publication fee comes in – paid by the authors.

The switch of income stream from readers to authors changes everything. Previously, publishers wanted to attract readers/subscribers, usually by presenting a high-quality product. Now they want to attract authors, even if no one reads it – it is now in the publisher’s interest to remove obstacles to acceptance and publication, obstacles like quality thresholds.

Some of the online journals are reputable, but given that anyone can set up an online journal (and so many have) and given that there is money to be made from doing so, they are now popping up all over the place. There now are tens of thousands of scientific journals and the number is increasing rapidly.

To prove that you can now get anything published, one researcher submitted a fake article (that should have been detected as meaningless) to 304 online journals and received an acceptance from over half of them, along with a bill for the publication fee.

Another example came from a frustrated researcher who submitted a paper titled ‘Get me off your f***ing mailing list’ in response to a spam email request from a journal, and had it accepted – pending payment, of course.

Predatory publishing works on a business model, the aim of which (as always) is to make as much money as possible. In order to increase revenue, predatory publishers send emails out to researchers everywhere, inviting them to submit their manuscript, and then accept everything that is submitted (I get requests to submit papers to questionable journals and conferences almost daily).

For predatory conferences (rather than journals), the organisers accept all the submitted presentations and then get the authors to register for the conference. The fee for registration at the conference (in order to present the paper) might be €500, so you can see how easy it is to make money from this. The conferences often comprise a bunch of perplexed researchers from different fields who turn up to the venue only to find each other, and no participants.

But the line between real and fake is not clear. The people submitting articles to these journals and conferences are real researchers, and often the people running the journals have a scientific background. Peer review is often a hidden (‘closed’) process anyway, so we have no way of telling if the manuscript was properly reviewed. And the submitted articles are published, and are accessible on the web. So how do we know what is ‘predatory’ or fake? There are lists of predatory publishers available, but it is still possible to work around the rules. When you look into this, however, you find that there is a continuous spectrum of legitimacy; it is not a yes/no phenomenon.

Researchers will always be judged by the quality of the journals in which they publish, but by trying to measure the legitimacy of the journals we are missing the point. The legitimacy of the journal doesn’t matter; the emphasis of our scrutiny should be on the validity of the individual scientific studies, not on where they were published, or even the people who wrote them – those things are only very rough guides.

Are these predatory publishers lowering the standard of science? They may be lowering the average by increasing the amount of poor quality research, but they aren’t touching the top tier. The trick is to know the difference; another reason to have a good understanding of the scientific method.

WHAT CAN THE FUNDERS DO?

Those who fund research have the ability to control what happens in the research community, and those who fund health care have control over what operations get done – there are very few surgeons out there operating for free.

Researchers are highly dependent on grant funding, so the funding process is a great place to effect change. Funding placebo surgical trials, or other well designed trials of surgery, should be a priority, not something to be avoided based on spurious ethical grounds or on a perceived lack of feasibility. And as more trials get done, the objections will be harder to justify.

Health insurers are in a unique position: they control payment for surgery, but they also exist in a competitive market. As a pure insurance company, it is in their interest to insure as many procedures as possible; as long as the premiums are adjusted accordingly, they will have a profit margin attached to each procedure. For the insurer, high turnover means high profit. This is why private health insurers even fund alternative medicine: to get more customers, not to improve the health of those customers.

But the health insurers also have information that can be useful to determine effectiveness and they can influence surgical practice without being draconian. One large private organisation in the US has highly complex data systems within its network, and that data has been used to feed back to clinicians and to steer practice away from ineffective treatments. This is a much more acceptable way of changing practice than simply cutting rebates. If the clinicians are involved in the process and accept the evidence, then the decision to avoid surgery will also be much more acceptable to the treating surgeon and the patient.

Government regulators have control if the government is the payer, like Medicare in the US and nationalised health care systems in other countries. In Australia, there is a list of which investigations and procedures are eligible for rebates. Unfortunately, though, these are not routinely updated.

There is movement towards disinvestment in ineffective or low-value health care. Until recently, new operations were being added to rebate lists regularly, but very few were being removed. Some progress has been made in this area, and the Choosing Wisely program has already been mentioned.

NICE (UK’s National Institute for Health and Care Excellence) have developed a ‘do not do’ database of investigations and treatments that should be discontinued. If you search ‘surgical procedures’, you find hundreds of ‘do not do’ interventions, although very few are about performing the operation; they usually refer to ways of doing surgery, and other treatments given with surgery. Still, it is a good reference for things in medicine that don’t work.

Still in the UK, the National Institutes for Health Research have been established to address questions of effectiveness and answer many of the unanswered questions.

One of the most effective but perhaps difficult things for funders to do is to insist that new treatments only be used (and funded) if they are part of a high-quality trial to determine their effectiveness. I would rather see 50 per cent of patients treated with a new treatment as part of a trial, and consequently find out with some certainty whether or not the treatment is effective, than to see everyone treated without ever knowing how effective the treatment is.

WHAT CAN SOCIETY DO?

Any change in society’s values is likely to happen slowly. A newspaper will sell more copies if it reports that the local hospital has just installed a robot to perform surgery than if it reports that comparative studies have shown that robotic surgery only adds cost, not benefit. But this won’t always be the case. Just as perceptions of historical events, political leaders and commercial brands can change, so can society’s perception of medicine.

I can see change coming, but I can also see cost and complexity in medicine rising in the meantime, often without clear scientific evidence of an associated benefit. While change may come from individuals, it can also be driven by those in power. Governments can demand better evidence for new (and established) procedures. Surgical procedures can be brought under stricter controls, like those used for drugs. And this can be done in a way that is acceptable to society by engaging clinicians (doctors who work directly with patients) and making it easier to perform the type of research that is necessary to demonstrate effectiveness.

Clinician engagement in the process of practice change is essential for two reasons: clinicians provide content expertise, and their involvement increases the acceptability of any change – after all, they are the ones who will be changing their practice.

Much has been written about the idea of embedding research into practice, and removing some of the unnecessary barriers to research that currently exist. The ethics of allowing unproven procedures to be performed needs to be balanced against the ethics of a placebo study of that particular procedure. Currently, ethics committees do not consider the former, only the latter.

And finally, governments can directly educate people, at a population level and at an individual patient level. At a population level, governments in Australia have been very active in reducing smoking rates through advertising campaigns, warning labels and changes to packaging, and these measures have been successful in changing behaviour at the individual level and in changing the collective attitude towards smoking. Australia has one of the lowest rates of smoking in the world, largely due to public education, legislation (against advertising) and the associated cultural changes.

At a patient level, governments and health services can support better informed, shared decision making projects aimed at giving the patient more responsibility in the decision making process, and the information needed to take on that role.

Members of the community can also get involved in research, in choosing which procedures need to be tested and which outcomes are important to them, and being involved in all aspects of the research process, from the ethics committee to the dissemination of the results.

Public education programs can also change attitudes to life’s predicaments, and prevent those predicaments from being medicalised. Back pain is common, but is usually self-limiting, and its chronicity and severity is associated with psychosocial factors more than physical factors. There is evidence that mass media campaigns aimed at changing population attitudes can influence clinician and patient behaviour. The message need not be complex, but by promoting positive beliefs, reducing negative beliefs and encouraging self-management strategies, change can be achieved on a large scale.

Education regarding the self-limiting nature of many symptoms, of the potential harms of medicalising complaints, and of the benefits of self-managing minor complaints is a realistic proposition, but it is difficult for individual clinicians to do this without support from larger organisations in society (academia, professional bodies, funders, government).

What might be stretching things is to expect governments to educate people in critical thinking. Society has embraced science as the best way of knowing things, but this has allowed anything that sounds even remotely scientific to be accepted as true. Society needs to be more sceptical when advertisements state that a product has been ‘subjected to clinical trials’ (I cringed when I heard this in an advertisement for a dietary supplement), without any mention of the results of those trials. Perhaps the trials showed that the product was worse than its competitors, or was completely ineffective? To the public, the words ‘clinical trials’ convey scientific legitimacy.

In Australia, societies of sceptics spend a lot of time and money challenging those who make false claims. There have been some wins in court (against the anti-vaccinators, for example) but at great cost, and those wins are outnumbered by the many complaints to consumer watchdogs and other government regulators that have gone unanswered. Even the universities have come under criticism for teaching alternative medicine – turning a blind eye to their scientific credentials to fill a gap in the market. I applaud the work of sceptical societies, but they have one flaw: they rarely (if ever) turn their scepticism towards mainstream medicine. I guess it would muddy their attacks on alternative medicine and their position that mainstream medicine is science-based.

It is a hard battle, but it is being won, slowly. When I was a kid, people believed all sorts of crazy things, but a steady increase in the acceptance and understanding of science as a way of estimating the truth has changed the landscape. People are already more sceptical of fanciful claims than they used to be, and I believe that this trend will continue.

Surgery, in particular, is gradually being brought into line and it would be unfair of me not to acknowledge the excellent work that is being done worldwide by governments, insurers, industry, journals, universities and surgeons to improve the evidence base for surgery. I am also pleased that many of my colleagues in orthopaedic surgery are leading the way in making surgery more scientific, by establishing quality registries, performing large-scale randomised trials, setting guidelines and standards, and researching important, patientrelevant questions. Because of this gradual move towards science-based medicine, surgeons today are much more aware of biases and of the scientific principles involved in evidence-based medicine, and surgery is better for it. The surgery I see performed today, and the surgeons performing it, are much more evidence-based than when I began practice. I am confident that the future will continue to hold less ineffective surgery than the past, and we can all contribute to that trend by being sceptical, asking the right questions and demanding the answers, rather than assuming effectiveness based on tradition or opinion.

° ° °

The main message of this book is that some surgical procedures, including many that are commonly performed, are possibly no more effective than placebo. Some may even be harmful, for no significant gain. Some procedures are effective in some people, but are often done on people for whom there is little benefit. And, for many effective operations, the real benefit is less than we think, and the harms are greater than we think.

I do not wish to leave the reader with the impression that all surgery is ineffective. There are many effective surgical operations that are common and lead to large benefits for patients – I just haven’t mentioned them in this book. In my own field, I get great satisfaction (as do my patients) out of one of the most common orthopaedic procedures: surgery for hip fractures in older patients. Another procedure that falls within my specialty, total hip replacement, was named the operation of the century in an article in The Lancet in 2007. Indeed, one of the most cost-effective interventions in all fields of medicine is a surgical procedure – cataract surgery. For as little as a few dollars in developing countries, and a few hundred dollars in developed countries, clear vision can be restored. That procedure is frequently performed across the world cheaply, effectively and with very few complications. My wish is to see more of that kind of effective surgery and less of the questionable or ineffective surgery, but that will only happen when we all start asking the right questions, and demand the evidence that allows us to determine the difference.

REFERENCES

THIS SECTION IS FOR those who wish to explore some topics further. I have not referenced every claim in the book, as I would for a scientific manuscript, but I have listed the main references for each chapter, in the order in which they occur. I have not added comments, but have provided enough information so that the articles or books can be easily located and the reader can go directly to the source.

1 The placebo effect

Cochrane A, Effectiveness and efficiency: random reflections on health services, Taylor & Francis, London, 1999

Kahneman D, Thinking, fast and slow, Penguin, London, 2011

Linden A, ‘Assessing regression to the mean effects in health care initiatives’, BMC Medical Research Methodology 2013, 13:119

Friedlaender GE et al., ‘Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions’, Journal of Bone and Joint Surgery (American) 2001, 83 Suppl 1(Pt 2):151–58

Gibson JNA, Waddell G, ‘Surgery for degenerative lumbar spondylosis’, Cochrane Database of Systematic Reviews 2005, Issue 4, Art. No.: CD001352

Moerman D, Meaning, medicine and the ‘placebo effect’, Cambridge University Press, Cambridge, 2002

2 The science of medicine – or lack of it

Simmons JP, Nelson LD, Simonsohn U, ‘False-positive psychology: undisclosed flexibility in data collection and analysis allows presenting anything as significant’, Psychological Science 2011, 22:1359

Ioannidis JPA, ‘Why most published research findings are false’, PLoS Medicine 2005, 2(8):e124

Begley CG, Ellis LM, ‘Drug development: raise standards for preclinical cancer research’, Nature 2012, 483:531–33

Prinz F, Schlange T, Asadullah K, ‘Believe it or not: how much can we rely on published data on potential drug targets?’, Nature Reviews Drug Discovery 2011, 10:712

Ioannidis JP, ‘Contradicted and initially stronger effects in highly cited clinical research’, Journal of the American Medical Association 2005, 294(2):218–28

Prasad V, ‘A decade of reversal: an analysis of 146 contradicted medical practices’, Mayo Clinic Proceedings 2013, 88(8):790–98

Open Science Collaboration, ‘Estimating the reproducibility of psychological science’, Science 2015, 349(6251):aac4716

‘Trouble at the lab’, Economist 19 October 2013

Adie S, Harris IA, Ma D, Naylor JM, Craig J, ‘Quality of conduct and reporting of meta-analyses of surgical interventions’, Annals of Surgery 2015, 261(4):685–94

Adie S, Harris IA, Naylor JM, Mittal R, ‘CONSORT compliance in surgical randomized trials: are we there yet? A systematic review’, Annals of Surgery 2013, 258(6):872–78

Bhandari, M et al., ‘Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials’, Canadian Medical Association Journal 2004, 170(4):477–80

Lexchin J, Bero LA, Djulbegovic B, Clark O, ‘Pharmaceutical industry sponsorship and research outcome and quality: systematic review’, British Medical Journal 2003, 326(7400):1167–70

Cooper JD, ‘Paying the piper: the NETT strikes a sour note’, Annals of Thoracic Surgery 2001, 72(2):330–33

National Emphysema Treatment Trial Research Group, ‘A randomized trial comparing lung-volume–reduction surgery with medical therapy for severe emphysema’, New England Journal of Medicine 2003, 348:2059–73

Tiong LU et al., ‘Lung volume reduction surgery for diffuse emphysema’, Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD001001

Cohen D, ‘How safe are metal-on-metal hip implants?’, British Medical Journal 2012, 344:e1410

3 Building the perfect placebo

Stampfer MJ, Colditz GA, ‘Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence’, Preventive Medicine 1991, 20(1):47–63

Writing Group for the Women’s Health Initiative Investigators, ‘Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial’, Journal of the American Medical Association 2002, 288(3):321–33

The Women’s Health Initiative Steering Committee, ‘Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the women’s health initiative randomized controlled trial’, Journal of the American Medical Association, 2004, 291(14):1701–12

Women’s Health Initiative Investigators, ‘Combined postmenopausal hormone therapy and cardiovascular disease: toward resolving the discrepancy between observational studies and the Women’s Health Initiative clinical trial’, American Journal of Epidemiology 2005, 162(5):404–14

Krieger N et al., ‘Hormone replacement therapy, cancer, controversies, and women’s health: historical, epidemiological, biological, clinical, and advocacy perspectives’, Journal of Epidemiology and Community Health 2005, 59(9):740–48

Moerman D, Meaning, medicine and the ‘placebo effect’, Cambridge University Press, 2002

Wabar RL, ‘Commercial features of placebo and therapeutic efficacy’, Journal of the American Medical Association 2008, 299(9):1016–17

McLean TR, ‘Discontinuation of Vioxx’, Lancet 2005, 365(9453):25

Carragee EJ, ‘The vertebroplasty affair: the mysterious case of the disappearing effect size’, Spine Journal 2010, 10(3):191–92

Welch HG, ‘Presumed benefit: lessons from the American experience with marrow transplantation for breast cancer’, British Medical Journal 2002, 324:1088

Kaptchuk TJ et al., ‘Sham device v inert pill: randomised controlled trial of two placebo treatments’, British Medical Journal 2006, 332(7538):391–97

Zhang W et al., ‘The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials’, Annals of the Rheumatic Diseases 2008, 67(12):1716–23

4 Putting surgery to the (placebo) test

Wartolowska K et al., ‘Use of placebo controls in the evaluation of surgery: systematic review’, British Medical Journal 2014, 348:g3253

Cobb LA et al., ‘An evaluation of internal-mammary-artery ligation by a double-blind technic’, New England Journal of Medicine 1959, 260(22):1115–18

Freeman TB, Vawter DE, Leaverton PE, Godbold JH, Hauser RA, Goetz CG, Olanow CW, ‘Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson’s disease’, New England Journal of Medicine 1999, 341:988–92

Macklin R, ‘The ethical problems with sham surgery in clinical research’, New England Journal of Medicine 1999, 341:992–96

Olanow CW et al., ‘A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease’, Annals of Neurology 2003, 54(3):403–14

Freed CR et al., ‘Transplantation of embryonic dopamine neurons for severe Parkinson’s disease’, New England Journal of Medicine 2001, 344(10):710–19

McRae C et al., ‘Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial’, Archives of General Psychiatry 2004, 61(4):412–20

Thomsen J, Bretlau P, Tos M, Johnsen NJ, ‘Meniere’s disease: endolymphatic sac decompression compared with sham (placebo) decompression’, Annals of the New York Academy of Science 1981, 374:820–30

Thomsen J, Bretlau P, Tos M, Johnsen NJ, ‘Placebo effect in surgery for Meniere’s disease: three-year follow-up’, Otolaryngology Head and Neck Surgery 1983, 91(2):183–86

Bretlau P, Thomsen J, Tos M, Johnsen NJ, ‘Placebo effect in surgery for Meniere’s disease: nine-year follow-up’, American Journal of Otology 1989, 10(4):259–61

Thomsen J et al., ‘The non-specific effect of endolymphatic sac surgery in treatment of Meniere’s disease: a prospective, randomized controlled study comparing “classic” endolymphatic sac surgery with the insertion of a ventilating tube in the tympanic membrane’, Acta Oto-laryngolica 1998, 118(6):769–73

Dowson A, ‘Migraine Intervention with STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache’, Circulation 2008, 117(11): 1397–404

Carroll JD, ‘Migraine Intervention with STARFlex Technology trial: a controversial trial of migraine and patent foramen ovale closure’, Circulation, 2008, 117(11):1358–60

Moseley JB et al., ‘A controlled trial of arthroscopic surgery for osteoarthritis of the knee’, New England Journal of Medicine 2002, 347:81–88

Kirkley A et al., ‘A randomized trial of arthroscopic surgery for osteoarthritis of the knee’, New England Journal of Medicine 2008, 359(11):1097–1107

Herrlin S et al., ‘Arthroscopic or conservative treatment of degenerative medial meniscal tears: a prospective randomised trial’, Knee Surgery, Sports Traumatology, Arthroscopy 2007, 15(4):393–401

Laupattarakasem W, Laopaiboon M, Laupattarakasem P, Sumananont C, ‘Arthroscopic debridement for knee osteoarthritis’, Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD005118

Sihvonen R et al. for the Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group, ‘Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear’, New England Journal of Medicine 2013, 369:2515–24

Katz JN et al., ‘Surgery versus physical therapy for a meniscal tear and osteoarthritis’, New England Journal of Medicine 2013, 368:1675–84

Thorlund JB, Juhl CB, Roos EM, Lohmander LS, ‘Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms’, British Medical Journal 2015, 350:h2747

Englund M, et al., ‘Incidental meniscal findings on knee MRI in middle-aged and elderly persons’, New England Journal of Medicine 2008, 359(11):1108–15

Freeman BJ et al., ‘A randomized, double-blind, controlled trial: intradiscal electrothermal therapy versus placebo for the treatment of chronic discogenic low back pain’, Spine 2005, 30(21):2369–77

Pauza KJ et al., ‘A randomized, placebo-controlled trial of intradiscal electrothermal therapy for the treatment of discogenic low back pain’, Spine Journal 2004, 4(1):27–35

Saal JA, Saal JS, ‘Intradiscal electrothermal treatment for chronic discogenic low back pain: prospective outcome study with a minimum 2-year follow-up’, Spine 2002, 27(9):966–73

Garden RS, ‘Tennis elbow’, Journal of Bone and Joint Surgery (Britain) 1961, 43B(1):100–106

Solheim E, Hegna J, Øyen J, ‘Extensor tendon release in tennis elbow: results and prognostic factors in 80 elbows’, Knee Surgery, Sports Traumatology, Arthroscopy 2011, 19(6):1023–27

Kroslak M, ‘Surgical treatment of lateral epicondylitis: a prospective, randomised, blinded, placebo controlled pilot study’, Faculty of Medicine, UNSW, 2012, Masters Thesis, <http://unsworks.unsw.edu.au/fapi/datastream/unsworks:10864/SOURCE01?view=true>

Sayesh E, Strauch R, ‘Does nonsurgical treatment improve longitudinal outcomes of lateral epicondylitis over no treatment? A metaanalysis’ Clinical Orthopaedics and Related Research 2015, 473(3):1093–1107.

Carragee EJ, ‘The vertebroplasty affair: the mysterious case of the disappearing effect size’, Spine Journal 2010, 10(3):191–92

Buchbinder R et al., ‘A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures’, New England Journal of Medicine 2009, 361:557–68

Kallmes DF et al., ‘A randomized trial of vertebroplasty for osteoporotic spinal fractures’, New England Journal of Medicine 2009, 361:569–79

Buchbiner R, Kallmes DF, ‘Vertebroplasty: when randomized placebocontrolled trial results clash with common belief ’, Spine Journal 2010, 10(3):241–43

Staples MP et al., ‘Effectiveness of vertebroplasty using individual patient data from two randomised placebo controlled trials: metaanalysis’, British Medical Journal 2011, 343:d3952

Bhatt DL, ‘A controlled trial of renal denervation for resistant hypertension’, New England Journal of Medicine 2014, 370:1393–1401

Messerli FH, Bangalore S, ‘Renal denervation for resistant hypertension?’, New England Journal of Medicine 2014, 370:1454–57

5 The surgical scrap heap

Fisher B et al., ‘Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer’, New England Journal of Medicine 2002, 347:1233–41

Veronesi U et al., ‘Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer’, New England Journal of Medicine 2002, 347:1227–32

Narod SA, Iqbal J, Giannakeas V, Sopik V, Sun P, ‘Breast cancer mortality after a diagnosis of ductal carcinoma in situ’, Journal of the American Medical Association Oncology 2015, 1(7):888–96

Houssami N et al., ‘Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy’, European Journal of Cancer 2010, 46(18):3219–32

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Poortmans PM et al., ‘Impact of the boost dose of 10 Gy versus 26 Gy in patients with early stage breast cancer after a microscopically incomplete lumpectomy: 10-year results of the randomised EORTC boost trial’, Radiotherapy and Oncology 2009, 90(1):80–85

van Dongen JA et al., ‘Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial’, Journal of the National Cancer Institute 2000, 92(14):1143–50

Freeman W, Watts JW, ‘The surgical relief of mental pain,’ Bulletin of the New York Academy of Medicine 1942, 18(12):794–812

The EC/IC Bypass Study Group, ‘Failure of extracranial–intracranial arterial bypass to reduce the risk of ischemic stroke – results of an international randomized trial’, New England Journal of Medicine 1985, 313:1191–1200

Shetty VD, Vowler SL, Krishnamurthy S, Halliday AE, ‘Clinical diagnosis of medial plica syndrome of the knee: a prospective study’, Journal of Knee Surgery 2007, 20(4):277–80

Nakayama A, Sugita T, Aizawa T, Takahashi A, Honma T, ‘Incidence of medial plica in 3,889 knee joints in the Japanese population’, Arthroscopy 2011, 27(11):1523–27

Boles CA, Butler J, Lee JA, Reedy ML, Martin DF, ‘Magnetic resonance characteristics of medial plica of the knee: correlation with arthroscopic resection’, Journal of Computer Assisted Tomography 2004, 28(3):397–401

Kim SJ, Lee DH, Kim TE, ‘The relationship between the MPP test and arthroscopically found medial patellar plica pathology’, Arthroscopy 2007, 23(12):1303–8

6 Today’s placebo surgeries

Lim HC, Adie S, Naylor JM, Harris IA, ‘Randomised trial support for orthopaedic surgical procedures’, PloS One 2014, 9(6):e96745

Focus on health: geographic variations in health care, OECD, September 2014, <www.oecd.org/els/health-systems/FOCUS-on-Geographic-Variations-in-Health-Care.pdf>

Deyo R, ‘Epidemiology of spinal surgery: rates and trends’, School of Public Health, University of Washington, <http://depts.washington.edu/ccor/studies/SpineSurgEpi.shtml>

Street JT et al., ‘Morbidity and mortality of major adult spinal surgery: a prospective cohort analysis of 942 consecutive patients’, Spine Journal 2012, 12(1):22–34

Schoenfeld AJ, Ochoa LM, Bader JO, Belmont PJ Jr, ‘Risk factors for immediate postoperative complications and mortality following spine surgery: a study of 3475 patients from the National Surgical Quality Improvement Program’, Journal of Bone and Joint Surgery (American) 2011, 93(17):1577–82

Deyo R et al., ‘Trends, major medical complications, and charges associated with surgery for lumbar spinal stenosis in older adults’, Journal of the American Medical Association 2010, 303(13):1259–65

Brook M et al., ‘Reoperation rates following lumbar spine surgery and the influence of spinal fusion procedures’, Spine 2007, 32(3):382–87

Gibson JNA, Waddell G, ‘Surgery for degenerative lumbar spondylosis’, Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD001352

Deyo RA, Nachemson A, Mirza SK, ‘Spinal-fusion surgery – the case for restraint’, New England Journal of Medicine 2004, 350:722–26

Rajaee SW, Bae HW, Kanim LEA, Delamarter RB, ‘Spinal fusion in the United States: analysis of trends from 1998 to 2008’, Spine 2012, 37(1):67–76

Weinstein JN, ‘United States trends and regional variations in lumbar spine surgery: 1992–2003’, Spine 2006, 31(23):2707–14

Andersson GBJ, ‘Epidemiological features of chronic low-back pain’, Lancet 1999, 354(9178):581–85

Harris IA, Dao AT, ‘Trends of spinal fusion surgery in Australia: 1997 to 2006’, ANZ Journal of Surgery 2009, 79(11):783–88

Brox JI et al., ‘Randomized clinical trial of lumbar instrumented fusion and cognitive intervention and exercises in patients with chronic low back pain and disc degeneration’, Spine 2003, 28(17):1913–21

Fairbank J, ‘Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial’, British Medical Journal 2005, 330(7502):1233

Fritzell Pvet al., ‘2001 Volvo Award Winner in Clinical Studies: Lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish Lumbar Spine Study Group’, Spine 2001, 26(23):2521–32

Hancock MJ et al., ‘Assessment of diclofenac or spinal manipulative therapy, or both, in addition to recommended first-line treatment for acute low back pain: a randomised controlled trial’, Lancet 2007, 370(9599):1638–43

Bialosky JE et al., ‘A randomized sham-controlled trial of a neurodynamic technique in the treatment of carpal tunnel syndrome’, Journal of Orthopaedic and Sports Physical Therapy 2009, 39(10):709–23

Juratli SM, Mirza SK, Fulton-Kehoe D, Wickizer TM, Franklin GM, ‘Mortality after lumbar fusion surgery’, Spine 2009, 34(7):740–47 Zamboni P et al., ‘A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency’, Journal of Vascular Surgery 2009, 50(6):1348–58

Morovic S, Zamboni P, ‘CCSVI is associated with multiple sclerosis’, Neurological Research 2012, 34(8):770–79

Friedemann P, Wattjes MP, ‘Chronic cerebrospinal venous insufficiency in multiple sclerosis: the final curtain’, Lancet 2014, 383(9912):106–108

Traboulsee AL et al., ‘Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study’, Lancet 2014, 383(9912):138–45

Siddiqui AH et al., ‘Prospective randomized trial of venous angioplasty in MS (PREMiSe)’, Neurology 2014, 83(5):441–49

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Shoupe D et al., ‘Elective oophorectomy for benign gynecological disorders’, Menopause 2007, 14(3 Pt 2):580–85

Jacoby VL et al., ‘Oophorectomy vs ovarian conservation with hysterectomy: cardiovascular disease, hip fracture, and cancer in the Women’s Health Initiative Observational Study’, Archives of Internal Medicine 2011, 171(8):760–68

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Alfirevic Z, Devane D, Gyte GML, ‘Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour’, Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD006066

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McLachlan H et al., ‘Effects of continuity of care by a primary midwife (caseload midwifery) on caesarean section rates in women of low obstetric risk: the COSMOS randomised controlled trial’, BJOG: An International Journal of Obstetrics & Gynaecology 2012, 119:1483–92

Khunpradit S et al., ‘Non-clinical interventions for reducing unnecessary caesarean section’, Cochrane Database of Systematic Reviews 2011, Issue 6. Art. No.: CD005528

Järvinen TLN, Sihvonen R, Englund M, ‘Arthroscopy for degenerative knee – a difficult habit to break?’, Acta Orthopaedica 2014, 85(3):215–17

Thorlund JB, Juhl CB, Roos EM, Lohmander LS, ‘Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms’, British Medical Journal 2015, 350:h2747

Varadhan KK, Neal KR, Lobo DN, ‘Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trial’, British Medical Journal 2012, 344:e2156

Bakhai A, Hill RA, Dundar Y, Dickson RC, Walley T, ‘Percutaneous transluminal coronary angioplasty with stents versus coronary artery bypass grafting for people with stable angina or acute coronary syndromes’, Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004588

Greenhalgh J et al., ‘Drug-eluting stents versus bare metal stents for angina or acute coronary syndromes’, Cochrane Database of Systematic Reviews 2010, Issue 5. Art. No.: CD004587

Boden WE et al., ‘Optimal medical therapy with or without PCI for stable coronary disease’, New England Journal of Medicine 2007, 356:1503–16

Stergiopoulos K, Brown DL, ‘Initial coronary stent implantation with medical therapy vs medical therapy alone for stable coronary artery disease’, Archives of Internal Medicine 2012, 172(4):312–19

Fox KA et al., ‘Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome: a meta-analysis of individual patient data’, Journal of the American College of Cardiology 2010, 55(22):2435–45

Lin GA, Dudley RA, Redberg RF, ‘Cardiologists’ use of percutaneous coronary interventions for stable coronary artery disease’, Journal of the American Medical Association Internal Medicine 2007, 167(15):1604–1609

Prasad V, Rho J, Cifu A, ‘The inferior vena cava filter: how could a medical device be so well accepted without any evidence of efficacy?’, Journal of the American Medical Association Internal Medicine 2013, 173(7):493–95

The PREPIC Study Group, ‘Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prévention du Risque d’Embolie Pulmonaire par Interruption Cave) randomized study’, Circulation 2005, 112:416–22

White RH, ‘High variation between hospitals in vena cava filter use for venous thromboembolism’, Journal of the American Medical Association Internal Medicine 2013, 173(7):506–12

Haut ER et al., ‘The effectiveness of prophylactic inferior vena cava filters in trauma patients: a systematic review and meta-analysis’, Journal of the American Medical Association Surgery 2014, 149(2):194–202

Coghlan JA, Buchbinder R, Green S, Johnston RV, Bell SN, ‘Surgery for rotator cuff disease’, Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD005619

Moss SW, ‘Floating kidneys: a century of nephroptosis and nephropexy’, Journal of Urology 1997, 158(3):699–701

Srirangam SJ, Pollard AJ, Adeyoju AAB, O’Reilly PH, ‘Nephroptosis: seriously misunderstood?’, BJU International 2009, 103:296–300

Thompson PM, Barber NJ, ‘Nephroptosis and nephropexy – hung up on the past?’, European Urology 2004, 46(4):428–33

Wilkins R, Bisson LJ, ‘Operative versus nonoperative management of acute Achilles tendon ruptures: a quantitative systematic review of randomized controlled trials’, American Journal of Sports Medicine 2012, 40(9):2154–60

Jiang N, Wang B, Chen A, Dong F, Yu B, ‘Operative versus nonoperative treatment for acute Achilles tendon rupture: a metaanalysis based on current evidence’, International Orthopaedics 2012, 36(4):765–73

Khan RJK, Carey Smith RL, ‘Surgical interventions for treating acute Achilles tendon ruptures’, Cochrane Database of Systematic Reviews 2010, Issue 9. Art. No.: CD003674

Swank DJ et al., ‘Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomised controlled multi-centre trial’, Lancet 2003, 361(9365):1247–51

Handoll HHG, Ollivere BJ, Rollins KE, ‘Interventions for treating proximal humeral fractures in adults’, Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD000434

Randgan A et al., ‘Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial’, Journal of the American Medical Association 2015, 313(10):1037–47

Ansari U, Adie S, Harris IA, Naylor JM, ‘Practice variation in common fracture presentations: a survey of orthopaedic surgeons’, Injury 2011, 42(4):403–407

Abudou M, Chen X, Kong X, Wu T, ‘Surgical versus non-surgical treatment for thoracolumbar burst fractures without neurological deficit’, Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD005079

Gnanenthiran SR, Adie S, Harris IA, ‘Nonoperative versus operative treatment for thoracolumbar burst fractures without neurologic deficit: a meta-analysis’, Clinical Orthopaedics and Related Research 2012, 470(2):567–77

Limb D, Shaw DL. Dickson RA, ‘Neurological injury in thoracolumbar burst fractures’, Journal of Bone and Joint Surgery (British) 1995, 77B(5):774–77

Bindal V et al., ‘Review of contemporary role of robotics in bariatric surgery’, Journal of Minimal Access Surgery 2015, 11(1):16–21

Singh I, ‘Robotics in urological surgery: review of current status and maneuverability, and comparison of robot-assisted and traditional laparoscopy’, Computer Aided Surgery 2011, 16(1):38–45

Coelho RF et al., ‘Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a critical review of outcomes reported by highvolume centers’, Journal of Endourology 2010, 24(12): 2003–15

Weinberg L, Rao S, Escobar PF, ‘Robotic surgery in gynecology: an updated systematic review’, Obstetrics and Gynecology International 2011 doi:10.1155/2011/852061

Trastulli S et al., ‘Robotic resection compared with laparoscopic rectal resection for cancer: systematic review and meta-analysis of shortterm outcome’, Colorectal Disease 2012, 14: e134–e156

AlAsri S, Min BS, ‘Robotic colorectal surgery: a systematic review’, ISRN Surgery 2012, doi:10.5402/2012/293894

Gurusamy KS, Samraj K, Fusai G, Davidson BR, ‘Robot assistant versus human or another robot assistant in patients undergoing laparoscopic cholecystectomy’, Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD006578

Gibbons L et al., ‘The global numbers and costs of additionally needed and unnecessary caesarean sections performed per year: overuse as a barrier to universal coverage’, World Health Report 2010, Background Paper, 30

Wennberg J, ‘Commentary: a debt of gratitude to J. Alison Glover’, International Journal of Epidemiology 2008, 37(1):26–29

7 Why do we still do it?

Illich I, Limits to medicine: medical nemesis, the expropriation of health, Marion Boyers, London, 1976

Adie S, Dao A, Harris IA, Naylor JM, Mittal R, ‘Satisfaction with joint replacement in public versus private hospitals: a cohort study’, ANZ Journal of Surgery 2012, 82(9):616–24

Wessely S, Nimnuan C, Sharpe M, ‘Functional somatic syndromes: one or many?’, Lancet 1999, 354(9182):936–39

Hatcher S, Arroll B, ‘Assessment and management of medically unexplained symptoms’, British Medical Journal 2008, 336(7653):1124–8

Aaron LA, Buchwald D, ‘A review of the evidence for overlap among unexplained clinical conditions’, Annals of Internal Medicine 2001, 134(9 Pt 2):868–81

Yunus MB, ‘Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes’, Seminars in Arthritis and Rheumatism 2007, 36(6):339–56

Goldacre B, Bad pharma, Fourth Estate, London, 2012

Angell M, The truth about drug companies, Random House, New York, 2004

Moynihan R, Cassels A, Selling sickness: how the world’s biggest pharmaceutical companies are turning us all into patients, Allen & Unwin, Sydney, 2005

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Adie S, Harris IA, Naylor JM, Mittal R, ‘CONSORT compliance in surgical randomized trials: are we there yet? A systematic review’, Annals of Surgery 2013, 258(6):872–78

Adie S, Harris IA, Ma D, Naylor JM, Craig J, ‘Quality of conduct and reporting of meta-analyses of surgical interventions’, Annals of Surgery 2015, 261(4):685–94

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Savovic J et al., ‘Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials’, Annals of Internal Medicine 2012, 157(6):429–38

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Cohen SP et al., ‘Epidural steroid injections compared with gabapentin for lumbosacral radicular pain: multicenter randomized double blind comparative efficacy study’, British Medical Journal 2015, 350:h1748

8 Surgery has a placebo effect – so what?

Weiser TG et al., ‘An estimation of the global volume of surgery: a modelling strategy based on available data’, Lancet, 2008, 372:139–44

Australian Commission on Safety and Quality in Health Care, Windows into safety and quality in health care, ACSQHC, Sydney, 2008

Wilson R, Runciman WB, Gibberd RW, Harrison BT, Newby L, Hamilton JD, ‘The Quality in Australian Health Care Study’, Medical Journal of Australia 1995, 163(6):458–71

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Mitchell CR et al., ‘20-Year survival after radical prostatectomy as initial treatment for cT3 prostate cancer’, BJU International 2012, 110(11):1709–13

Wilt TJ et al., ‘Radical prostatectomy versus observation for localized prostate cancer’, New England Journal of Medicine 2012, 367:203–13

Narod SA, Iqbal J, Giannakeas V, Sopik V, Sun, ‘Breast cancer mortality after a diagnosis of ductal carcinoma in situ’, Journal of the American Medical Association Oncology 2015, 1(7):888–96

Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA, ‘Twenty-five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial’, British Medical Journal 2014, 348:g366

Gøtzsche PC, Jørgensen KJ, ‘Screening for breast cancer with mammography’, Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001877

Benjamin DJ, ‘The efficacy of surgical treatment of cancer – 20 years later’, Medical Hypotheses 2014, 82(4):412–20

9 What can we do about it?

Kahneman D, Thinking, fast and slow, Penguin, London, 2011

Stacey D et al., ‘Decision aids for people facing health treatment or screening decisions’, Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD001431

Wilson R, Runciman WB, Gibberd RW, Harrison BT, Newby L, Hamilton JD, ‘The Quality in Australian Health Care Study’, Medical Journal of Australia 1995, 163(6):458–71

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ACKNOWLEDGEMENTS

I HAVE DELIBERATELY kept the production of this book separate from my work. I have made it unlike a scientific manuscript, and more like a collection of ideas and studies designed to convince the reader to change their way of thinking regarding the effectiveness of surgery. Consequently, the research team with which I work have had no direct input into the book, although they have performed some of the research mentioned in the book. However, I would like to acknowledge them, and my employers, for their contribution to making my job successful and enjoyable, and giving me the academic freedom and support to pursue the areas of research that are of greatest interest to me.

My wife deserves special thanks for her undying support of my pursuits, whether they be clinical, academic, administrative or otherwise. There is one thing for certain: without her, you would not be reading this book.

I thank the team at NewSouth Publishing for taking me on and for their guidance.

Lastly, I would like to thank my colleagues. There are many academics that I have followed and learned from over the years, and many surgeons who have inspired and guided me – too many to name individually. I am often asked if my opinions and writings land me in hot water with my fellow surgeons and it constantly surprises me that it doesn’t, and that, for the most part, they are supportive and interested in my work. And many are enthusiastic, particularly when it involves the kind of research that answers some of the unanswered surgical questions.

In fact, the book began many years ago when I was asked by a colleague to give the Hamilton Russell oration at the Royal Australasian College of Surgeons Annual Scientific Congress. I chose to give a talk that was the seed of this book – the idea of exploring the placebo effect of surgery, and the idea that procedures that are generally accepted as being effective might be otherwise.