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On Stopping a Randomized Clinical Trial for Futility

Chapter
Part of the Applied Bioinformatics and Biostatistics in Cancer Research book series (ABB)

Abstract

This chapter reviews the art and science of planned interim futility analyses in clinical trials that test a superiority hypothesis. Our goal is to recommend “best practices.” We briefly describe situations where we find terminating trials for futility advisable and not advisable. This chapter outlines four statistical methods of interim futility analysis – conditional power, predictive power, group sequential testing, and basing an interim futility analysis on a Phase 2 outcome or biomarker instead of on the primary efficacy variable. We distinguish between trials where the locus of control resides in the investigators from those where the commercial sponsor controls the trial. We provide guidance, based on our experience and opinion, as to types of trials where each method is preferable. We describe several practical issues that arise in the use of interim futility analysis, for example, lag in treatment effect, time patterns in development of evidence of efficacy, unreliability of early data, efficacy endpoints that take long follow-up to observe, and choice of timing of futility analysis. Finally, we consider the ethics of futility analyses including public disclosure of their results. A conclusion section summarizes our recommendations for the use of interim futility analysis.

Keywords

Interim Analysis Vagus Nerve Stimulator Data Monitoring Committee Conditional Power Drift Parameter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We thank Catherine Conlon for preparing Fig. 5.4. We are grateful to David Sackett for his insightful comments on an earlier version of this chapter.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of BiostatisticsJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  2. 2.IDDI ConsultantsInternational Drug Development InstituteLouvain-la-NeuveBelgium
  3. 3.Department of BiostatisticsHasselt UniversityDiepenbeekBelgium
  4. 4.Statistics Collaborative, Inc.WashingtonUSA

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