Advances in Clinical Trials in the Twentieth Century

Abstract

▪ Abstract This article considers the rise of the randomized clinical trial during the twentieth century. Before such development could begin, probability and statistics needed to merge. Sir RA Fisher introduced randomization in the 1920s and, beginning in the 1930s and 1940s, randomized clinical trials in humans were being performed by using the statistical-hypothesis-testing paradigm. Randomization gave unbiased comparisons and a way to perform hypothesis testing without model assumptions. To preserve the benefits of randomization, a type of analysis called intent-to-treat analysis is appropriate. Needed development has occurred and is occurring in refining ethical standards, monitoring trials of serious irreversible endpoints while preserving type-I error, and instituting independent data- and safety-monitoring boards. Recent methodology has also been concerned with the appropriateness of using surrogate endpoints. A current area of debate is the appropriateness of using Bayesian statistical methods in this context.