2018 Bragg UNSW Press Prize for Science Writing

November 27, 2018

Dr Andrew Leigh MP won the 2018 Bragg UNSW Press Prize for Science Writing with ‘From bloodletting to placebo surgery’, an excerpt from his book Randomistas. The piece looks at the fascinating effects of sham surgeries and the history of randomised trials.

The Copyright Agency’s Cultural Fund has sponsored the Bragg Prize for the next three years, which includes the major prize, the student prize and the publication, The Best Australian Science Writing 2018.

The $7000 winner’s prize was presented by Professor Emma Johnston AO, Dean, UNSW Science, at a ceremony hosted by UNSW Press and UNSW Science on 6 November 2018. Runners-up prizes of $1500 each were awarded to Jo Chandler for ‘Amid fear and guns, polio finds a refuge’ and Margaret Wertheim for ‘Radical Dimensions’. Preethika Mathan from Santa Sabina College, NSW, won this year’s Bragg Student Prize for her essay ‘i-Care’. Read it here.

The Bragg UNSW Press Prize for Science Writing is an annual prize for the best short non-fiction piece on science written for a general audience. It is named in honour of Australia’s first Nobel laureates, William Henry Bragg and his son William Lawrence Bragg.

Dr Andrew Leigh’s award-winning piece is reprinted, with permission, below.

From bloodletting to placebo surgery

Andrew Leigh

From Randomistas: How Radical Researchers Changed Our World

Copyright (c) Andrew Leigh 2018

Reprinted by permission of La Trobe University Press, an imprint of Schwartz Publishing

Standing in a sparkling white operating theatre, I’m watching my first surgery. On the bed is a 71-year-old patient having her hip replaced. Around the room are nurses, an anaesthetist, a representative of the company that makes the artificial hip, and an observing doctor. In the centre, gently slicing open the woman’s hip with a scalpel is Melbourne surgeon Peter Choong. Easylistening music plays from the stereo. The atmosphere in the room couldn’t be calmer. It’s a familiar operation, and the team know each other well.

First incision made, Peter puts down his scalpel, and picks up a bipolar diathermy machine. Now he’s burning the flesh instead of slicing it, a technique that reduces bleeding and speeds recovery. The room smells like a barbecue. Back to the scalpel, and a few minutes later Peter is in to the hip joint. To clean it out, he uses a device like a power drill. On the end is a metal sphere the size of a ping-pong ball, its rough surface designed to shave the hip socket until it’s perfectly smooth. When he pulls it out, the ball is covered in bone and blood. Not for the first time, I’m glad I ate a light breakfast.

Modern surgery is a curious combination of brawn, technology and teamwork. One moment, Peter is swinging a hammer or lifting a knee joint. Next, he is fitting a prosthesis, watching a computer screen as crosshairs indicate precisely the angle of fit. The tension rises when the bone cement is mixed. As soon as the two compounds are combined, a nurse begins calling time: ‘Thirty seconds … one minute … one minute 30.’ At four minutes, it’s inserted into the patient. At five minutes, the artificial joint is attached. Everyone in the room knows the cement will be hard at 10 minutes. After that, the only way to change the angle of the prosthesis is to chip the hardened cement out from inside the bone.

In an operating theatre, the surgeon is in command. And yet for all his expertise, Peter is surprisingly willing to admit what he doesn’t know. Is it better to perform hip surgery from the front (anterolateral) or the back (posterolateral)? Should we encourage obese patients to get a lap-banding operation before knee surgery? How early should we get patients out of bed after a joint replacement? For antiseptic, is it best to use iodine, or does the cheaper chlorhexidine perform equally well?

Over the coming years, Peter hopes to answer each of these questions. His main tool: the randomised trial. A few years ago he led a team that conducted a randomised trial to test whether total knee replacement was better done the conventional way, or with computer guidance to help line up the implant. Across 115 patients, the study showed that computer assistance led to a more accurate placement of the artificial knee, and higher quality of life for patients. In other studies, he has randomised particular surgical techniques and strategies for pain management post-surgery.

Most controversially, Peter Choong is a strong supporter of evaluating surgical operations against a control group who receive ‘placebo surgery’. For control group patients, this typically means that the surgeon makes an incision and then sews them up again.

Placebo surgery – also known as ‘sham surgery’ – is used when researchers are uncertain whether or not an operation helps patients. In one famous study, surgeons tested whether keyhole knee surgery helped patients with osteoarthritis. At the time, the operation was performed more than a million times a year around the world. But some surgeons had doubts about its effectiveness. So in the late 1990s a group of surgeons in Houston conducted an experiment in which some patients received keyhole surgery, while others simply received an incision on their knee. Only when the surgeon entered the operating suite did an assistant hand them an envelope saying whether the surgery would be real or sham. Because the patients were under a local anaesthetic, the surgeons made sure patients were kept in the operating theatre for the same length of time as in the real operation, and manipulated the knee as they would for a surgery. Two years later, patients who received sham surgery experienced the same levels of pain and knee function as patients who had real surgery.

Sham surgery dates back to 1959, when a group of Seattle doctors became sceptical of a technique used to treat chest pain by tying tiny knots in chest arteries. They randomly performed the experiment on eight patients, and simply made incisions in the chests of another nine. The study found that the technique had no impact, and the surgery was phased out within a few years.

In recent years, sham surgery has shown no difference between a control group and osteoporosis patients who have bone cement injected into cracked vertebrae (a procedure known as vertebroplasty). Sham surgery has even been performed by neurosurgeons, who found that injecting foetal cells into the brains of patients suffering from Parkinson’s disease had no more effect than the placebo treatment, in which patients had a small hole, known as a burr hole, drilled into the side of their skulls.

The most stunning sham surgery result came in 2013. After the finding that knee surgery didn’t help older patients with osteoarthritis, a team in Finland began to wonder about the knee surgery performed for a torn meniscus, the piece of cartilage that provides a cushion between the thighbone and shinbone. Their randomised experiment showed that among middle-aged patients, surgery for a torn meniscus was no more effective than sham surgery. This operation, known as a meniscectomy, is performed millions of times a year, making it the most common orthopaedic procedure in countries such as Australia and the United States. While some surgeons acknowledged the enormous significance of the finding, others were not so receptive. An editorial in the journal Arthroscopy thundered that sham surgery randomised trials were ‘ludicrous’. The editors went so far as to argue that because no ‘right-minded patients’ would participate in sham surgeries, the results would ‘not be generalizable to mentally healthy patients’.

Yet sham surgeries are growing in importance, as people realise that the placebo effect in surgery is probably bigger than in any other area of medicine. A recent survey of 53 sham surgery trials found that the treatment only outperformed the placebo 49 per cent of the time. But in 74 per cent of cases, patients appeared to respond to the placebo. In other words, three out of four patients feel that a surgery has made them better, even though half of the evaluated surgeries don’t work as intended. The results suggest that millions of people every year are undergoing surgeries that make them feel a bit better; yet they would feel just as good if they had undergone placebo surgery instead.

Such a huge placebo effect is probably explained by the fact that surgery is a more invasive procedure than other medical interventions, and by the particularly high status of surgeons. As the joke goes, people are waiting in the cafeteria line in heaven when a man in a white coat cuts in and takes all the food. ‘Who’s that?’ one asks. ‘It’s just God,’ another replies. ‘He thinks he’s a surgeon.’ Yet the results of sham surgery trials suggest that the profession is far from infallible. For nearly half of the procedures that have been evaluated in this way, the surgeon might as well have started by asking the patient: ‘Would you prefer the full operation, or should we just cut you open, play a few easy-listening tracks and then sew you back up again?’

Ethical questions will continue to be one of the main issues confronting sham surgery. In the 1990s one surgical text stated baldly that ‘sham operations are ethically unjustifiable’. To confront this, researchers have gone to extraordinary lengths to ensure patients understand what is going on. In the Houston knee surgery trial, patients were required to write on their charts: ‘On entering this study, I realize that I may receive only placebo surgery. I further realize that this means that I will not have surgery on my knee joint. This placebo surgery will not benefit my knee arthritis.’ Surgeons explain to each patient that the reason for the randomised trial is that the world’s leading experts truly do not know whether the surgery works, a situation known as ‘clinical equipoise’. Because we are uncertain about the results of the treatment, it is possible that those who get the sham surgery may in fact be better off than those who get the real surgery.

Despite the advocacy of surgeons such as Peter Choong, sham surgery remains in its infancy. A study of orthopaedic surgeries in Sydney hospitals found that only about one-third of procedures were supported by a randomised trial. Sydney surgeon Ian Harris points out that patients sometimes regard aggressive surgeons as heroic and conservative surgeons as cowardly. Yet ‘if you look beyond the superficial you often find that the heroic surgeon will have bad results … it is harder, and possibly more courageous, to treat patients without surgery’. Harris notes that more aggressive surgeons are less likely to be criticised and less likely to be sued, and get paid a lot more.

Pittsburgh orthopaedic surgeon John Christoforetti tells of how the randomised evidence led him to advise a patient not to seek knee surgery for a meniscal tear. The man responded by going online and giving the surgeon a one-star rating and a rude comment. The patient firmly believed he needed the operation. ‘Most of my colleagues,’ Christoforetti says, ‘will say: “Look, save yourself the headache, just do the surgery. None of us are going to be upset with you for doing the surgery. Your bank account’s not going to be upset with you for doing the surgery. Just do the surgery.” ’ Sometimes it can be easier to ignore the evidence than to follow it.

* * * * *

In the Bible, the book of Daniel tells the story of an early medical experiment. King Nebuchadnezzar is trying to persuade Daniel and three other young men from Judah to eat the royal delicacies. When Daniel replies that they would prefer a vegetarian diet, he is told that they may end up malnourished. To settle the matter, the king agrees that for 10 days the four young men will eat only vegetables, and will then be compared with youths who have eaten the royal delicacies. At the end of the experiment, Daniel and the other three are in healthier condition, so are allowed to remain vegetarian.

Daniel’s experiment wasn’t a random one, since he and his colleagues chose to be in the treatment group. But the Bible’s 2200-year-old experiment was more rigorous than the kind of ‘pilot study’ sometimes we still see, which has no comparison group at all.

In the ensuing centuries, randomised medical trials steadily advanced. In the 1540s French surgeon Ambroise Paré was a battlefield surgeon charged with tending to soldiers who had been burned by gunpowder. For these men, the chances of survival were grim. A few years earlier, in the Battle of Milan, Paré had found three French soldiers in a stable with severe burns. As he recounted in his autobiography, a passing French soldier asked if there was any way of curing them. When Paré said there was nothing that could be done, the soldier calmly pulled out his dagger and slit their throats. Paré told him he was a ‘wicked man’. The soldier replied that if it had been him in such pain, he hoped someone would cut his neck rather than let him ‘miserably languish’.

Now Paré was responsible for an even larger group of burned soldiers. A bag of gunpowder had been set alight, and many Frenchmen had been wounded. He began applying the remedy of the day: boiling oil mixed with treacle. But at a certain point, he ran out of hot oil and switched to an old Roman remedy: turpentine, oil of roses and egg white. The next morning, when he checked the two groups of soldiers, Paré found that those who had been treated with boiling oil were feverish, while those who had received the turpentine (which acted as a disinfectant) had slept well. ‘I resolved with myself,’ he wrote, ‘never so cruelly to burn poor men wounded with gunshot.’

By the standards of today, Paré’s experiment has its flaws. Suppose he had begun treating the most badly burned soldiers first, and then moved on to those with lighter injuries. In that case, we might expect those treated with oil to be in a worse condition, regardless of the effect of the remedy. Yet while Paré’s study was imperfect, medicine continued to inch towards more careful analysis. Two centuries after Paré, Lind would conduct his scurvy experiment on a dozen patients who were ‘as similar as I could have them’.

An important step on the road towards today’s medical randomised trials was the notion that patients might be more inclined to recover – or at least to report that they were feeling better – after seeing a doctor. In 1799 British doctor John Haygarth became frustrated at the popularity of a quack treatment known as ‘Perkins tractors’. The tractors were simply two metal rods, which were to be held against the body of the patient to ‘draw off the noxious electric fluid’ that was hurting the patient. In an experiment on five rheumatic patients, Haygarth showed that wooden rods performed just as well as Perkins tractors, giving rise to the idea of the placebo.

The placebo, Haygarth pointed out, was one reason why famous doctors might produce better results than unknown ones. If authoritative doctors evoked a larger placebo effect, he reasoned, then their patients might be more likely to recover, even if their remedies were useless. And indeed, the air of authority was highly prized by doctors of the time, despite the poor quality of their remedies. One of the main treatments used by doctors was bloodletting, which involved opening a vein in the arm with a special knife, and served only to weaken patients. It wasn’t until the early 1800s that a randomised trial of bloodletting was conducted on sick soldiers. The result was a 29 per cent death rate among men in the treatment group and a 2 per cent death rate in the control group. Medicine’s bloody history is memorialised in the name of one of the discipline’s top journals: The Lancet. Before there was evidence-based medicine, there was eminence-based medicine.

In 19th-century Vienna, high-status doctors were literally costing lives. At a time when many affluent women still gave birth at home, Vienna General Hospital largely served underprivileged women. The hospital had two maternity clinics: one in which babies were delivered by female midwives, and the other where babies were delivered by male doctors. Patients were admitted to the clinics on alternate days. And yet the clinics had very different health outcomes. In the clinic run by midwives, a mother’s chance of death was less than 1 in 20. In the clinic run by doctors, maternal mortality was 1 in 10: more than twice as high. Patients knew this and would beg not to be admitted into the doctor-run clinic. Some would give birth on the street instead of in the doctors’ clinic, because their chance of survival was higher.

To Ignaz Semmelweis, the doctor in charge of records, the results were puzzling. Because the two clinics admitted patients on alternate days, the health of the patients should have been similar. Indeed, it was almost as though the Vienna Hospital had set up a randomised trial to test the impact of the two clinics, and discovered the doctors were doing more harm than good. In trying to uncover reasons for this, Semmelweis first observed that midwives delivered babies while women lay on their sides, while doctors delivered babies while women lay on their backs. But when the doctors tried adopting side delivery, it didn’t help. Then he noted that when a baby died, the priest walked through the ward with a bell; he theorised that this might be terrifying the other mothers. But removing the priest’s bell also had no impact.

Then a friend of Semmelweis was poked by a student’s scalpel while doing an autopsy, and died. Noticing that his friend’s symptoms were similar to those of many of the mothers who died, Semmelweis theorised that doctors might be infecting mothers with ‘cadaverous particles’, causing death by puerperal fever. He insisted that doctors wash their hands with chlorine from then on, and the death rate plummeted. Only thanks to Semmelweis and an accidental randomised trial did it become safer to give birth attended by a Viennese doctor than on the streets.

And yet, like Lind’s findings, Semmelweis’s insistence on handwashing was rejected by many medical experts of the time. The germ theory of disease was yet to be developed. Many doctors were insulted by the suggestion that the hands of gentlemen like themselves were unclean, and by the implication that they were responsible for infecting their patients. After Semmelweis left the Vienna General Hospital, chlorine handwashing was discontinued.

In the mid-1800s, large elements of medicine remained profoundly unscientific. Addressing the Massachusetts Medical Society in 1860, physician Oliver Wendell Holmes Sr said, ‘I firmly believe that if the whole materia medica [body of medical knowledge], as now used, could be sunk to the bottom of the sea, it would be all the better for mankind, and all the worse for the fishes.’ As historian David Wootton noted in Bad Medicine, his 2006 book on the history of medical missteps: ‘For 2400 years patients have believed that doctors were doing good; for 2300 years they were wrong.’

* * * * *

Slowly medical researchers came to rely less on theory and more on empirical tests. At the end of the 19th century, diphtheria was the most dangerous infectious disease in the developed world, killing hundreds of thousands of people annually. To test the impact of serum treatment, Danish doctor Johannes Fibiger devised a randomised trial. Like the Vienna maternity hospitals, Fibiger assigned people to alternate treatments on alternate days. He found that patients given the serum were nearly four times less likely to die. The demand for Fibiger’s treatment was so great that in 1902 the Danish government founded the State Serum Institute to produce and supply the vaccine to its citizens.

In the coming decades, randomised medical trials became more common. In the 1930s researchers suggested that the risk of investigators biasing their results could be significantly reduced if the person administering the drugs did not know which was the control and which was the treatment. Trials in which the identity of the treatments was hidden from both the patient and the administering doctor became known as ‘double-blind’ studies. In one telling, the term came from blindfold tests that the Old Gold cigarette company carried out to promote its products.

In the 1940s a randomised trial showed that antibiotics did not cure the common cold. A trial in 1954 randomly injected 600 000 US children with either polio vaccine or salt water. The vaccine proved effective, and immunisation of all American children began the following year. The 1960s saw randomised trials used to test drugs for diabetes and blood pressure, and the contraceptive pill. Strong advocates of evidence-based medicine, such as Alvan Feinstein and David Sackett, argued that the public should pay less attention to the prestige of an expert and more to the quality of their evidence.

One of the best-known advocates of evidence-based medicine was Scottish doctor Archie Cochrane, whose early training was as a medical officer in German prisoner-of-war camps during World War II. In one camp, Cochrane was the only doctor to 20 000 men. They were fed about 600 calories a day (one-third of what is generally considered a minimum daily intake). All had diarrhoea. Epidemics of typhoid and jaundice often swept the camp. When Cochrane asked the Nazi camp commanders for more doctors, he was told: ‘Nein! Aerzte sind überflüssig.’ (‘No! Doctors are superfluous.’) Cochrane was furious.

But over time, Cochrane’s anger softened. When he considered which British men lived and died, Cochrane came to understand that his medical expertise had little impact. He did his best, but was up against the limits of 1940s therapies. As Cochrane later acknowledged, what little aid doctors could provide was largely ineffective ‘in comparison with the recuperative power of the human body’. This was particularly true when he cared for tuberculosis patients, tending to them in the clinic before officiating at their funerals (‘I got quite expert in the Hindu, Moslem, and Greek Orthodox rites’).

After the war, Cochrane wrote, ‘I had never heard then of “randomised controlled trials”, but I knew there was no real evidence that anything we had to offer had any effect on tuberculosis, and I was afraid that I shortened the lives of some of my friends by unnecessary intervention.’ Cochrane realised then that the Nazi officer who had denied him more doctors might have been ‘wise or cruel’, but ‘was certainly right’.

Reading Cochrane’s memoirs, it is hard not to be struck by his honesty, modesty and tenderness. He jokes that, ‘It was bad enough being a POW, but having me as your doctor was a bit too much.’ At another point, he tells the story of the night when the Germans dumped a young Russian soldier into the ward late one night. The man’s lungs were badly infected; he was moribund and screaming. Cochrane had no morphine, only aspirin, which did nothing to stop the Russian crying out. Cochrane did not speak Russian, nor did anyone else on the ward. Eventually, he did the only thing he could. ‘I finally instinctively sat down on the bed and took him in my arms, and the screaming stopped almost at once. He died peacefully in my arms a few hours later. It was not the pleurisy that caused the screaming but loneliness. It was a wonderful education about the care of the dying.’

In the final decades of his life, Cochrane challenged the medical profession to regularly compile all the relevant randomised controlled trials, organised by speciality. In 1993, four years after Cochrane’s death, British researcher Iain Chalmers did just that. Known at the outset as the Cochrane Collaboration – and today simply as Cochrane – the organisation systematically reviews randomised trials to make them accessible for doctors, patients and policymakers. Today, Cochrane reviews are one of the first places that doctors will go when they encounter an unfamiliar medical problem. Chalmers also created the James Lind Alliance, an initiative that identifies the top 10 unanswered questions for dozens of medical conditions: its aim is to guide future researchers towards filling in the gaps.

Thanks to the work of past medical randomistas, new drugs must now follow an established path from laboratory to market. Since the late 1930s, when an experimental drug killed more than a hundred Americans, most countries require initial safety testing to be done on animals. Typically, this involves two species, such as mice and dogs. If a drug passes these tests, then it moves into the clinical trial phase. Phase I trials test safety in humans, based on less than a hundred people. Phase II trials test the drug’s efficacy on a few hundred people. Phase III trials test effectiveness in a large group – from several hundred to several thousand – and compares it with other drugs. If a drug passes all these stages and hits the market, post-marketing trials monitor its impact in the general population and test for rare adverse effects.

What are the odds of success? A recent US study found that if you started with 10 drugs, four would be knocked out by Phase I trials. Four more would flunk Phase II trials. Of the remaining two drugs, one would either fail Phase III trials or get rejected by the Food and Drug Administration. In other words, only one in 10 drugs that look promising in laboratory and animal tests ends up finding its way onto the market. For drugs used to treat cancer and heart disease, the odds of a drug making its way from lab to market are lower still.

In each case, those taking the new drug are compared against people taking a fake drug. The word ‘placebo’ comes from the Latin placere, meaning ‘to please’. It reflects the fact that people can respond differently when they receive what they believe is an effective treatment. When medical researchers see a change in outcomes among people who have only taken sugar pills, they call it ‘the placebo effect’.

Early research on the placebo effect turns out to have overstated the power of placebos, wrongly conflating the natural tendency of patients to recover with the impact of placebos. Modern researchers now doubt that the placebo effect actually helps our bodies heal faster. But it does seem to affect self-reported impacts, such as pain. For alleviating discomfort, the placebo effect works in surprising ways. For example, placebo injections produce a larger effect than placebo pills. Even the colour of a tablet changes the way in which patients perceive its effect. Thanks to randomised trials, we know that if you want to reduce depression, you should give the patient a yellow tablet. For reducing pain, use a white pill. For lowering anxiety, offer a green one. Sedatives work best when delivered in blue pills, while stimulants are most effective as red pills. The makers of the movie The Matrix clearly knew this when they devised a moment for the hero to choose between a blue pill and a red pill. Blue would wipe his mind and make him happy; red would show him how truly terrifying the world is.

If we simply compare patients who take a pill with those who do not, then we might wrongly attribute the impact entirely to the active ingredients in the tablet. By contrast, a well-designed randomised trial strips out the placebo effect, for example, by comparing pain levels among patients who are given white sugar pills with pain levels among patients who are given identical-looking white aspirin tablets.

* * * * *

Patients with severe emphysema used to be treated with lung volume reduction surgery, until a randomised trial showed that it significantly increased the risk of death. After minor strokes, neurosurgeons would once routinely perform an extracranial to intracranial bypass (connecting an artery outside the skull with one inside the skull). The surgery was supported by case studies, but a randomised trial showed that it produced worse outcomes. For a patient whose bowel is caught up in scar tissue, experts used to favour laparoscopic surgery to ‘unpick’ the adhesions, until a randomised trial showed that this kind of surgery did not reduce pain or improve quality of life. Beta-blockers, which had previously been thought to endanger patients with heart disease, have now been shown in randomised trials to lower the chance of death.

Among postmenopausal women, early studies of those who chose to take hormone therapy suggested that the treatment might reduce the incidence of cardiovascular disease. By the turn of the 21st century, around 90 million hormone therapies were being prescribed for newly postmenopausal American women. Then randomised controlled trials showed that hormone therapy had only negative impacts: raising the risk of stroke and the risk of obstruction of a vein by a blood clot. For doctors, changing the advice they gave to patients wasn’t easy. As Chicago physician Adam Cifu describes his experience, ‘I had to basically run back all those decisions with women. And, boy, that really sticks with you, when you have patients saying, “But I thought you said this was the right thing.” ’

Medical ethics dictate that researchers should stop a trial if there is evidence of harm. Until the early 2000s, it was normal to treat severe head injuries with steroid injections. Then a 49-country trial began randomising patients to receive either a steroid injection or a placebo injection. Halfway through, researchers saw that the death rate among those who received the steroid was 21 per cent: considerably higher than the 18 per cent death rate among those who received a placebo. The results were conclusive enough to stop the study and publish the results. Head injury patients no longer get steroid injections as a routine matter.

Randomised trials have also helped doctors do a better job of screening. For years, doctors have responded to patients with non-specific back pain by ordering CT scans, MRIs or even X-rays. In recent years, randomised trials have shown that the results of such tests don’t help medical professionals treat pain. In fact, patients with back pain who were randomly assigned to get an X-ray ended up with a higher level of self-reported pain and more frequent follow-up visits to the doctor.

An even tougher area is cancer screening. If screening were error-free, it would be straightforward to roll it out. But it turns out that screening comes with costs as well as benefits. In a systematic review of randomised trials of breast cancer screening, Cochrane concluded that ‘for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings.’

The European Randomized Study of Screening for Prostate Cancer, covering men in the Netherlands, Belgium, Sweden, Finland, Italy, Spain and Switzerland, is now able to compare mortality rates 13 years after blood-test screening. With more than 160 000 men in the trial, the death rate is slightly lower for men who have been screened for prostate cancer (commonly known as ‘PSA screening’). But the difference is small – one death averted for every 781 men who are screened – and the researchers are not yet confident that they have enough evidence to justify prostate cancer screening for every man aged over 50.

* * * * *

For my own part, randomised trials have helped shape how I look after my health. I used to take a daily multivitamin tablet, until I read a study that drew together all the available randomised trials of vitamins A, C and E, beta carotene and selenium. The study found that for otherwise healthy people, there is no evidence that extra vitamins make you live longer. If anything, those who took vitamin supplements seemed to live shorter lives. Not wanting to send myself to an early grave, I stopped taking multivitamin tablets.

The same goes for fish oil. Based on a 2002 study, millions of people in advanced countries began popping pills made from mushed-up sardines and anchovies. Yet a decade later, a much larger, systematic review of randomised studies found no evidence that omega-3 supplements prevented heart attacks. So I dropped the fish oil tablet too.

As for the rest, I can’t help thinking of Tim Minchin’s beat poem ‘Storm’ every time I accidentally wander into the ‘herbal remedies’ section of the supermarket. In it, Tim imagines himself responding to an advocate of natural medicine:


‘By definition’, I begin

‘Alternative medicine’, I continue,

‘Has either not been proved to work,

Or been proved not to work.

Do you know what they call “alternative medicine”

that’s been proved to work? “Medicine”.


I love running, so I’m always on the lookout for randomised trials on exercise science. After reading randomised trials, I’ve opted to choose my running shoes based on comfort, moving away from the ‘stability’ models that I’d been wearing for many years. After a marathon, I’ll wear compression socks, since an Australian trial showed that they significantly boost recovery. When training, I’ll try to include some high-intensity bursts, based on a randomised trial that found that the cardiovascular benefits of sprint training are five times greater than for moderate exercise.

Around home, when I have to remove a band-aid from one of my sons, I’ll remind them that a randomised trial by James Cook University researchers found that the fast approach was less painful than the slow approach. When I sip my morning brew, I take pleasure in the randomised evidence showing that coffee protects against DNA breaks. And after reading the evidence on annual medical check-ups, I’m persuaded that they do not reduce my chance of falling ill, but do add to the cost of the health care system. For example, in the United States, annual physicals account for one-tenth of doctor visits, despite expert bodies recommending against them for people who aren’t showing any symptoms of illness.

Medical researchers were among the earliest pioneers of randomised trials. Indeed, I chose to start my book Randomistas with health care precisely because it’s so far ahead of many other fields. One of the reasons that modern medicine is saving more lives than ever before in human history is its willingness to test cures against placebos or the best available alternative. If it works, we use it; if not, it’s back to the lab. In just one field – strokes and neurological disorders – there are around 50 000 Americans alive today thanks to recent randomised trials. For every new treatment (AIDS drugs, the human papillomavirus vaccine, magnetic resonance imaging, genetic testing), medicine has discarded old ones (bloodletting, gastric freezing, routine circumcision and tonsillectomy).

But there is still more that medicine can do to benefit from randomised trials. As we have seen, surgical randomised trials remain comparatively rare, with hospitals conducting tens of thousands of medical procedures every year that are not supported by good evidence. Surgeon Ian Harris gives the example of spine fusion surgery for back pain, an operation now performed on 1 in 1000 Americans each year, even though randomised trials show no better results than for intensive rehabilitation. Harris notes that ‘the more you know, the harder it gets … a conflict develops between what you understand to be true, based on scientific research … and what everyone else is doing’. Surgeon and author Atul Gawande argues that ‘pointless medical care’ costs hundreds of billions of dollars annually. Each year, one in four Americans receives a medical test or treatment that has been proven through a randomised trial to be useless or harmful. An Australian study identified over 150 medical practices that are commonly used despite being unsafe or ineffective. The randomistas not only need to produce more evidence, they also need to do a better job at publicising what they know already.

For full details of the works cited, see the endnotes in Randomistas.