Why did I become a clinician-trialist?

In 1956, I went to the University of Illinois, College of Medicine to be taught how to become a physician. Despite the College’s well-deserved reputation, a recent therapeutic scandal was smouldering – and occasionally bursting into flames. The university’s Vice-President-Director was Dr Andrew Ivy, a famous gastrointestinal physiologist. He had represented the American Medical Association at the medical trials of Nazis in Nuremberg, and he subsequently became Executive Director of the National Advisory Cancer Council and a director of the American Cancer Society. Not long before my arrival at the College of Medicine, Dr Ivy had been accused of fraudulently claiming efficacy for a quack cancer remedy, Krebiozen, which turned out to be nothing more than creatine. None of my teachers (some of whom were involved in attempts to resolve the dispute) ever spoke about the scandal, but it had generated an atmosphere of skepticism towards authority figures, and this had fostered iconoclasm around the place, which appealed to me. By 1959, I had become a final-year medical student, and I once foundmyself responsible for a teenager who had been admitted to a medical ward with hepatitis. After a few days of enforced total bed rest – the standard management of the condition – his spirits and energy returned and he asked me to let him get up and around. I felt I needed to have a look at relevant evidence to guide my response to his request. I went to the library and came across a remarkable report for which the lead author was Tom Chalmers. A meticulously conducted randomised trial hadmade clear that there was no good evidence to justify requiring hepatitis patients to remain in bed after they feel well. Armed with this evidence, I convinced my supervisors to let me apologise tomy patient and encourage him to be up and about as much as he wished. His subsequent clinical course was uneventful. That report of a (factorial) randomised trial challenging the validity of two standard treatments for hepatitis – bed rest and low fat diet – helped to change my career. During my postgraduate training in internal medicine, the better I became at diagnosing my patients’ illnesses, the more frustrated I became at my profession’s collective ignorance about how I should treat them, or whether I should treat them at all. I came to the conclusion that there were four things wrong with the way that the experts were using their clinical observations to decide whether a treatment did more good than harm. More precisely, I was worried that these four ‘wrongs’ destroyed our ability to make ‘fair comparisons’ of the effects of different treatments. The validation of these worries both initiated and reinforced my decision to devote most of my career to randomised trials.