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Education And Debate

A change in scientific approach: from alternation to randomised allocation in clinical trials in the 1940s

BMJ 1999; 319 doi: (Published 28 August 1999) Cite this as: BMJ 1999;319:572
  1. P D'Arcy Hart, visiting scientist
  1. National Institute for Medical Research, London NW7 1AA

    The Medical Research Council undertook two controlled clinical trials of potentially curative drugs in the United Kingdom in the 1940s. The first trial, carried out in 1943-4 to investigate patulin treatment for the common cold, was arguably the first double blind curative trial with concurrent controls in the general population in modern times.1 It was also probably one of the last with non-randomised or quasi-randomised2 allocation of subjects, but it used technology of the highest order then available. The MRC Patulin Clinical Trials Committee (1943) was chaired by Sir Harold Himsworth, and its statisticians were M Greenwood and W J Martin.

    The second trial, carried out in 1947-8 to evaluate streptomycin in tuberculosis, is widely accepted as the first randomised curative trial.3 The MRC Streptomycin in Tuberculosis Trials Committee (1946) was chaired by Sir Geoffrey Marshall, and the statistician was Sir Austin Bradford Hill. As a member of the MRC scientific staff, I was secretary to both committees.

    Summary points

    The MRC undertook two controlled drug trials in the 1940s

    In a controlled, double blind mass trial of patulin for the common cold, subjects were allocated alternately to study groups

    In the first streptomycin trial, patients were allocated randomly to groups, but the trial was not double blind or placebo controlled

    Menaces such as HIV infection and multiple drug resistance have dampened the optimism enjoyed by researchers in the middle of this century

    Embedded Image

    Tuberculosis treatment in the 1940s: Broomfield Hospital, near Chelmsford

    (Credit: POPPERFOTO)

    Patulin trial

    During …

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