Monitoring of clinical trials: issues and recommendations

Control Clin Trials. 1993 Jun;14(3):183-97. doi: 10.1016/0197-2456(93)90002-u.

Abstract

Interim analyses of randomized trials enable investigators to make more efficient use of limited research resources and to satisfy ethical requirements that a regimen be discontinued as soon as it has been established to have an inferior efficacy/toxicity profile. Unfortunately, the integrity and credibility of these trials can be compromised if inappropriate procedures are used in monitoring interim data. In this paper we discuss how group sequential designs provide useful guidelines that enable one to satisfy the valid objectives of interim monitoring while avoiding undesirable consequences, and we consider how flexible one can be in the way such designs are implemented. We also provide motivation for the role of data-monitoring committees in preserving study integrity and credibility in either government- or industry-sponsored trials. In our view, these committees should have multidisciplinary representation and membership limited to individuals free of apparent significant conflict of interest, and ideally should be the only individuals to whom the data analysis center provides interim results on relative efficacy of treatment regimens. Finally, we discuss some important practical issues such as estimation following group sequential testing, analysis of secondary outcomes after using a group sequential design applied to a primary outcome, early stopping of negative trials, and the role of administrative analyses.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Clinical Trials as Topic / standards*
  • Clinical Trials as Topic / statistics & numerical data
  • Decision Making
  • Ethics, Professional
  • Female
  • Humans
  • Male
  • National Institutes of Health (U.S.)
  • Professional Staff Committees
  • Research Design
  • Stochastic Processes
  • United States