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Use of randomisation in early clinical trials

BMJ 1999; 318 doi: (Published 15 May 1999) Cite this as: BMJ 1999;318:1352

Theobald's trial in 1936 incorporated some aspects of randomisation

  1. Sjúr∂ur F Olsen, Senior epidemiologist (
  1. Maternal Nutrition Group of the Danish Epidemiology Science Centre, Statens Serum Institut, DK-2300 Copenhagen C, Denmark

EDITOR—The issue of 31 October marking 50 years of the randomised controlled trial, with historical accounts on trial methodology, made me look up the trial undertaken by Theobald. He studied the combined effect of calcium, vitamin A, and vitamin C supplementation on toxaemia in 100 pregnant women, apparently using true individual randomisation. 1 2 This was in 1936, a decade before the streptomycin trial.3

Although not all aspects of the randomisation procedure are entirely clear from Theobald's report, 1 2 he was obviously a thoughtful researcher. He provided evidence that the groups had similar age and parity distributions, had a statistician (E S Pearson) to assess the extent to which his results (that symptoms of toxaemia were less common in …

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