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July 15, 1994Statistics in Medicine578 citations

Interim analysis: The alpha spending function approach

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DDDavid L. DeMetsKLK. K. Gordon Lan

Key Points

  • Review the alpha spending function framework in group sequential clinical trials and illustrate its application to standard statistical methods.
  • Examined frequentist group sequential boundary designs used to control cumulative type I error inflation caused by repeated interim testing.
  • Evaluated the implementation and mathematical adaptability of the alpha spending function across various trial designs, including survival and longitudinal data analyses.
  • Alpha spending functions successfully preserve overall type I error rates while permitting flexibility in the number and timing of interim analyses.
  • The approach provides robust statistical boundaries applicable to time-to-event outcomes, repeated longitudinal measures, and complex multi-stage trial designs.

Abstract

Interim analysis of accumulating data in a clinical trial is now an established practice for ethical and scientific reasons. Repeatedly testing interim data can inflate false positive error rates if not handled appropriately. Group sequential methods are a commonly used frequentist approach to control this error rate. Motivated by experience of clinical trials, the alpha spending function is one way to implement group sequential boundaries that control the type I error rate while allowing flexibility in how many interim analyses are to be conducted and at what times. In this paper, we review the alpha spending function approach, and detail its applicability to a variety of commonly used statistical procedures, including survival and longitudinal methods.

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Cite This Study

DeMets et al. (1994) studied this question.

synapsesocial.com/papers/69d99c082a25b240b7a3d0d6https://doi.org/10.1002/sim.4780131308
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