title: Issues in the use of adaptive clinical trial designs.
abstract: Sequential sampling plans are often used in the monitoring of clinical trials in order to address the ethical and efficiency issues inherent in human testing of a new treatment or preventive agent for disease. Group sequential stopping rules are perhaps the most commonly used approaches, but in recent years, a number of authors have proposed adaptive methods of choosing a stopping rule. In general, such adaptive approaches come at a price of inefficiency (almost always) and clouding of the scientific question (sometimes). In this paper, I review the degree of adaptation possible within the largely prespecified group sequential stopping rules, and discuss the operating characteristics that can be characterized fully prior to collection of the data. I then discuss the greater flexibility possible when using several of the adaptive approaches receiving the greatest attention in the statistical literature and conclude with a discussion of the scientific and statistical issues raised by their use.
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington 9815, USA. semerson@u.washington.edu
authors.forename: Scott S
authors.initials: SS
authors.lastname: Emerson
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D006801:Humans; D012107:Research Design; D018401:Sample Size