Two-stage adaptive enrichment design for testing an active factor

J Biopharm Stat. 2020;30(1):18-30. doi: 10.1080/10543406.2019.1609015. Epub 2019 May 28.

Abstract

We propose an adaptive enrichment approach to test an active factor, which is a factor whose effect is non-zero in at least one subpopulation. We implement a two-stage play-the-winner design where all subjects in the second stage are enrolled from the subpopulation that has the highest observed effect in the first stage. We recommend a weighted Fisher's combination of the most powerful test for each stage, respectively: the first stage Hotelling's test and the second stage noncentral chi-square test. The test is further extended to cover binary outcomes and time-to-event outcomes.

Keywords: Active factor; adaptive enrichment trial; fisher’s combination; gene-treatment interaction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Clinical Trials as Topic / statistics & numerical data*
  • Catastrophization / genetics
  • Catastrophization / psychology
  • Catechol O-Methyltransferase / genetics
  • Data Interpretation, Statistical
  • Humans
  • Models, Statistical
  • Polymorphism, Single Nucleotide
  • Research Design / statistics & numerical data*
  • Shoulder Pain / genetics
  • Shoulder Pain / psychology

Substances

  • COMT protein, human
  • Catechol O-Methyltransferase