Controlled trials: the 1948 watershed

Clinical trials before 1946

Important scientific advances seldom occur out of the blue but can be seen in retrospect to have been the culmination of processes that have built up over the years. This was certainly true of the introduction of the new method of conducting clinical trials, first reported in 1948, that has played such a major part in the progress of clinical medicine in the last half century. When I qualified in medicine in 1937, new treatments were almost always introduced on the grounds that in the hands of professor A or in the hands of a consultant at one of the leading teaching hospitals, the results in a small series of patients (seldom more than 50) had been superior to those recorded by professor B (or some other consultant) or by the same investigator previously. Under these conditions variability of outcome, chance, and the unconscious (leave alone the conscious) in the selection of patients brought about apparently important differences in the results obtained; consequently, there were many competing new treatments. The treatment of peptic ulcer was, perhaps, more susceptible to claims of benefit than most other chronic diseases; so that in 1948, when I began to investigate it, I was soon able to prepare a list of treatments beginning with each letter of the alphabet. Standard treatments, for their part, tended to be passed from one textbook to another without ever being adequately evaluated.