“Controlled Trials: the 1948 Watershed”, 1998-10-31 (; backlinks):
Claims of therapeutic benefit are often misleading unless there are concurrent control groups
When treatments are allocated to alternate patients there is a risk of bias in the selection of patients
Randomly allocating individuals after entry into a trial eliminates bias and provides a proper estimate of random error
Randomisation can be done within strata of the likely response to treatment, if clinicians can define the strata sufficiently clearly
Ethical standards should be the same for therapeutic trials and routine care
Large numbers of participants may be needed in a trial if moderate yet important effects are to be detected
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. A few clinicians had realised that this was unsatisfactory and had called for the use of concurrent controls, usually suggesting that alternate patients should be treated by one or other of the 2 methods being compared…