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Keywords:

  • Adjusted p-value;
  • Error rate;
  • Flexible alpha splitting;
  • Gatekeeping;
  • Multiple tests

Abstract

Major objectives of a clinical trial are commonly stated in a hierarchical order as primary and secondary. The parallel gatekeeping testing strategy provides an opportunity to assess secondary objectives when all or partial primary objectives are achieved. The current available gatekeeping procedures have different pros and cons so users either need to justify the assumption associated with some procedures or tolerate suboptimal power performance of other procedures. By applying the Holm test with a flexible alpha splitting technique, we propose a procedure which (1) is powerful for assessing the primary objectives, (2) can be used when no assumption can be made on the dependency structure of test statistics, and (3) has the full flexibility to allocate user-preferred alpha to assess the secondary objectives based on the number of primary objectives achieved. A real clinical trial example is used for illustration of the proposed procedure.