Use of randomisation in the Medical Research Council's clinical trial of streptomycin in pulmonary tuberculosis in the 1940s

BMJ 1998; 317 doi: http://dx.doi.org/10.1136/bmj.317.7167.1220 (Published 31 October 1998)
Cite this as: BMJ 1998;317:1220

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  1. Alan Yoshioka, historian (alan_yoshioka@hotmail.com)
  1. Centre for History of Science, Technology and Medicine, Imperial College, London SW7 2AZ
  1. Correspondence to: Mr Yoshioka, PO Box 166, Pictou, NS B0K 1H0
  • Accepted 1 October 1998

A slight mystery surrounds the clinical trial that this special issue of the BMJ commemorates.1 It is now widely recalled that pulmonary tuberculosis patients in the Medical Research Council (MRC) trial were allocated to a streptomycin treatment group and a control group by a process using random sampling numbers and sealed envelopes (box). The editorial that introduced the MRC's report to BMJ readers on 30 October 1948 called attention to this new scheme, distinguishing it from the older practice of taking alternate cases in order of admission to hospital as the method of creating a control group.2 The statistician involved, Professor (later Sir) Austin Bradford Hill, had been promoting the use of random allotment since before the second world war.3 Remarkably, however, the word “random” appeared nowhere in the MRC's files on streptomycin for 1946. During that year, the now famous scheme was explicitly mentioned in a single letter. So why did the MRC use randomisation in this clinical trial?

Summary points

Randomised allocation of patients is rarely mentioned in the Medical Research Council's documents on streptomycin clinical trials

The meaning of the term “randomisation” has shifted over time; justifications for using randomisation have also changed

Streptomycin was isolated in 1943 at Rutgers University in New Jersey; the MRC began planning clinical trials in 1946; the first patients with tuberculosis entered the trials in 1947

The British government initially purchased 50 kg of American streptomycin for the MRC; most of the supply went to the clinical trial in pulmonary tuberculosis

Public demand for streptomycin was far in excess of supplies in Britain. Randomisation relieved the MRC's clinicians of responsibility for deciding who would be treated

Any answer is tentative as contemporary evidence about the reasoning of the members of the MRC's committee is thin. We can make some inferences …

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