Why the MRC therapeutic trials committee did not introduce controlled clinical trials

The failure of the Medical Research Council (MRC) Therapeutic Trials Committee (TTC) to introduce rigorously designed clinical trials of new medicines in the 1930s is now part of the standard account of the development of medical research in the UK. Historically, this appears significant because the TTC was active in the period immediately before the clinical trials of patulin and streptomycin which were also sponsored by the MRC, and did establish the modern principles of clinical trial design. Viewed from this side of the streptomycin trial in particular, the designs for clinical trials endorsed by the TTC seem curiously antiquated, displaying little regard for the scientific framework necessary for fair trials – comparison, control and the conscious avoidance of bias – which had become well-known during the period of its operation. Some explanation for this seems necessary. The TTC included the most eminent biomedical researchers of the day. It was aware of the problems arising from poor trial design – the serum trial for lobar pneumonia, which the TTC inherited and managed, was problematic precisely because it lacked rigorous trial design. Nor was the technique of random allocation particularly controversial – a few randomised trials had taken place under the auspices of the MRC well before World War II, for example, the trial of light therapy undertaken by Dora Colebrook in the late 1920s. Why then did the TTC not make use of the principles of clinical trial design, which were known to it, which would have increased the validity of its work, and were shortly to become the norm? A full explanation would need to include not just the change in the intellectual understanding of the design of clinical trials but also the organisational, social and political context in which clinical trials were conducted in the years 1920 to 1950. Such an undertaking is beyond the scope of the present work, but aspects of such an explanation for the UK are available in the literature, and for the USA in the work of Marks and Meldrum. This paper describes the origins and work of the TTC in detail in order to begin to understand its intentions, and the aspirations of its sponsoring body, the MRC, in the context of the clinical research landscape of the 1930s. Additional material and references are included in Toth.