History of Controlled Trials in Medicine

Rankin and Rivest recently published a piece looking at the use of clinical trials more than 400 years ago,[1] while Bothwell and Podolsky have produced a highly readable historical account of controlled trials.[2] Alternate treatment designs became quite popular in the late eighteenth century, but Austin Bradford Hill was concerned with the risk of ‘cheating’ and carried out an iconic RCT to overcome the problem.[3] But what next for the RCT? It is time to move to a Bayesian approach,[4] automate trials in medical record systems, and widen credible limits to include the risk of bias when follow-up is incomplete, therapist is not masked, or subjective outcomes are not effectively blinded.

— Richard Lilford, CLAHRC WM Director


  1. Rankin A & Rivest J. Medicine, Monopoly, and the Premodern State – Early Clincial Trials. N Engl J Med. 2016; 375(2): 106-9.
  2. Bothwell LE & Podolsky SH. The Emergence of the Randomized Controlled Trial. N Engl J Med. 2016; 375(6): 501-4.
  3. Hill AB. The environment and disease: Association or causation? Proc R Soc Med. 1965; 58(5): 295-300.
  4. Lilford RJ, & Edwards SJL. Why Underpowered Trials are Not Necessarily Unethical. Lancet. 1997; 350(9080): 804-7.

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