Introduction: The MRC Streptomycin trial which was published in the British Medical Journal in 1948 has gained a reputation as the first randomised controlled trial. However, although it was a well conducted and described study, it was not the earliest to use a random or quasi-random process to allocate patients to different treatments.
Objective: To demonstrate the need to look back earlier than 1948 if as complete a set as possible of randomised controlled trials (RCTs) and controlled clinical trials (CCTs) is to be obtained.
Methods: Sporadic examples of randomised and quasi-randomised trials from before the streptomycin trial are often cited, and re-cited, in discussions on the history of controlled trials. Among these are a study of pulmonary tuberculosis which was published in 1931 and used the flip of a coin to allocate patient groups to sanocrysin or placebo. There were also a number of trials that used quasi-random methods, such as alternate allocation, around this time. A random sample of BMJ and Lancet volumes from the 1930s and 1940s were searched to investigate the relative rarity of such examples.
Results: Approximately 1-3 reports of RCTs and CCTs were found in each sixmonth volume. These were predominantly CCTs, such as two trials that were printed back-to-back in the 11 December 1937 issue of the BMJ. Some pre-1948 RCTs have also been found, including two on breast-feeding in the Lancet in the second half of 1947.
Discussion: Although there are many fewer reports of RCTs and CCTs in the literature of half a century ago in comparison to now - perhaps a few per year in the BMJ or Lancet compared to about 100 in each today - such reports do exist. Thus, the determining factor in how far back to look should be the yield of relevant studies in the journal being searched, rather than a cut-off date derived from a trial which was neither the first to be randomised, nor the first to be controlled.