Issues in the use of adaptive clinical trial designs

Stat Med. 2006 Oct 15;25(19):3270-96; discussion 3302-4, 3320-5, 3326-47. doi: 10.1002/sim.2626.


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.

MeSH terms

  • Clinical Trials as Topic / methods*
  • Humans
  • Research Design*
  • Sample Size