An Investigation and Review of Futility Analysis Methods in Phase III Oncology Trials.

Abstract

The general objective of this thesis was to improve understandings of design, conduct and analysis of randomized controlled trials (RCTs). The specific objective was to evaluate the methodological and statistical principles associated with conducting analyses of futility, a component of interim analysis, as part of the conduct of RCTs. This objective was addressed by first performing a systematic review, which included a detailed literature search, as well as data from a cohort of previously extracted studies. The systematic review was designed to identify futility analysis principles and methodologies in order to inform the design and conduct of retrospective futility analyses of two completed NCIC CTG trials. The results of these trials have been previously published; one trial met its stated endpoint and the other did not. Neither trial underwent an interim analysis of futility during its conduct. The retrospective futility analyses assessed the accuracy of frequently used methods, by comparing the results of each method to each other and to the original final analysis results. These assessments were performed at selected time points using both aggressive and conservative stopping rules. In order to increase the robustness of the comparisons, bootstrapping methods were applied. The results of this thesis demonstrate principles associated with the conduct of futility analyses and provide a basis for hypotheses-testing of optimum methodologies and their associated trade-offs.