Shuffle the deck, flip that coin: randomization comes to medicine

There is a lot of confusion about the first use of randomization in an experiment and the first use of randomization in medicine. Some writers think that the great statistician R A Fisher carried out the first randomized trial (in agriculture)1 and published the results in 1923.2–5 Others think that the first medical trial was carried out by the British National Research Council in the 1940s.6,7 But there are earlier examples and we think we have found the oldest. Readers of this series will know that controlled trials are as old as Biblical Daniel,8 the evaluation of smallpox inoculation in 1721,9 the evaluation of Mesmerism in 1784,10 and Semmelweiss’s trials to reduce hospital infections.11 To resolve this debate we have to be precise in our definition of randomization in experiments. The word “randomization” does not exist in the Oxford English Dictionary or its supplement.12,13 It has two frequent uses in social science and clinical research. The first is a “random sample” from a larger population. Here randomization is used to ensure that the sample is representative of the population as a whole. The second use of randomization in experimental design is our focus here. There is an experiment, purposefully and prospectively designed; there are control and experimental interventions on patients purposefully designed to eliminate every observable and unobservable difference between the two except for the experimental intervention; and there is a method of assignment which is out …

[1]  E. Shezen,et al.  Embryonic Pig Pancreatic Tissue Transplantation for the Treatment of Diabetes , 2006, PLoS medicine.

[2]  D Neuhauser,et al.  Ignaz Semmelweis and the birth of infection control , 2004, Quality and Safety in Health Care.

[3]  D. Neuhauser,et al.  Daniel: using the Bible to teach quality improvement methods , 2004, Quality and Safety in Health Care.

[4]  M. Best,et al.  “Cotton Mather, you dog, dam you! I’l inoculate you with this; with a pox to you”: smallpox inoculation, Boston, 1721 , 2004, Quality and Safety in Health Care.

[5]  M. Best,et al.  Evaluating Mesmerism, Paris, 1784: the controversy over the blinded placebo controlled trials has not stopped , 2003, Quality & safety in health care.

[6]  David Cantor,et al.  The progress of experiment: science and therapeutic reform in the United States, 1900–1990 , 2002, Medical History.

[7]  Statistics on the Table , 2001 .

[8]  J. R. Scotti,et al.  Available From , 1973 .

[9]  C. Gluud.  Trials and errors in clinical research , 1999, The Lancet.

[10]  H. Marks,et al.  Reviews: Medicine and Health-The Progress of Experiment: Science and Therapeutic Reform in the United States, 1900-1990 , 1997 .

[11]  Joseph Brent,et al.  Charles Sanders Peirce: A Life , 1993 .

[12]  E. Stanley.  THE OXFORD ENGLISH DICTIONARY AND SUPPLEMENT: THE INTEGRATED EDITION OF 1989 , 1990 .

[13]  Laurence H. Baker,et al.  Clinical Trials: Design, Conduct, and Analysis , 1987 .

[14]  D. DeMets,et al.  Fundamentals of Clinical Trials , 1982 .

[15]  Stephen M. Stigler,et al.  American Contributions to Mathematical Statistics in the Nineteenth Century (Vol. I & II). , 1980 .

[16]  Waring Jj.  The chest service at Bellevue Hospital: a better mouse trap. , 1956 .

[17]  J. J. Waring.  The chest service at Bellevue Hospital: a better mouse trap. , 1956, American review of tuberculosis.

[18]  S. Toulmin,et al.  Philosophy of Science , 1970, The British Journal for the History of Science.

[19]  M. Daniels.  Streptomycin treatment of pulmonary tuberculosis. , 1949, Medical times.

[20]  N. D’Esopo,et al.  STREPTOMYCIN TREATMENT OF PULMONARY TUBERCULOSIS , 1998, The Journal of clinical investigation.

[21]  R. Fisher,et al.  STUDIES IN CROP VARIATION , 2009 .

[22]  J. Jastrow,et al.  On small differences in sensation , 1884 .