Sequential design and analysis in the randomized clinical trial: A historical perspective

Abstract Sequential analysis, as invented by Wald, was not targeted to clinical trials; in fact, the randomized clinical trial was being invented nearly simultaneously by Hill on the other side of the Atlantic. The connection to clinical trials was established by Bross and Armitage in the early 1950s and applied in a number of trials during that decade. Restrictions in its applicability in practice led to a dry spell until its resurgence with group sequential methods. This article reviews the historical context of the use of sequential analysis in actual randomized clinical trials. It does not review methodological developments, except as they relate to the historical and philosophical setting.