title: The shrinking or disappearing observed treatment effect.
abstract: It is frequently noted that an initial clinical trial finding was not reproduced in a later trial. This is often met with some surprise. Yet, there is a relatively straightforward reason partially responsible for this observation. In this article, we examine this reason by first reviewing some findings in a recent publication in the Journal of the American Medical Association. To help explain the non-negligible chance of failing to reproduce a previous positive finding, we compare a series of trials to successive diagnostic tests used for identifying a condition. To help explain the suspicion that the treatment effect, when observed in a subsequent trial, seems to have decreased in magnitude, we draw a conceptual analogy between phases II-III development stages and interim analyses of a trial with a group sequential design. Both analogies remind us that what we observed in an early trial could be a false positive or a random high. We discuss statistical sources for these occurrences and discuss why it is important for statisticians to take these into consideration when designing and interpreting trial results.
authors.affiliation: Statistical Research and Consulting Center, Pfizer Inc, Michigan, USA.
authors.forename: Christy
authors.initials: C
authors.lastname: Chuang-Stein
authors.forename: Simon
authors.initials: S
authors.lastname: Kirby
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D036262:Empirical Research; D006801:Humans; D016896:Treatment Outcome
keywords: overestimation; regression to the mean; shrinkage