Optimal multiple testing and design in clinical trials

Ruth Heller*, Abba Krieger, Saharon Rosset

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

A central goal in designing clinical trials is to find the test that maximizes power (or equivalently minimizes required sample size) for finding a false null hypothesis subject to the constraint of type I error. When there is more than one test, such as in clinical trials with multiple endpoints, the issues of optimal design and optimal procedures become more complex. In this paper, we address the question of how such optimal tests should be defined and how they can be found. We review different notions of power and how they relate to study goals, and also consider the requirements of type I error control and the nature of the procedures. This leads us to an explicit optimization problem with objective and constraints that describe its specific desiderata. We present a complete solution for deriving optimal procedures for two hypotheses, which have desired monotonicity properties, and are computationally simple. For some of the optimization formulations this yields optimal procedures that are identical to existing procedures, such as Hommel's procedure or the procedure of Bittman et al. (2009), while for other cases it yields completely novel and more powerful procedures than existing ones. We demonstrate the nature of our novel procedures and their improved power extensively in a simulation and on the APEX study (Cohen et al., 2016).

Original languageEnglish
Pages (from-to)1908-1919
Number of pages12
JournalBiometrics
Volume79
Issue number3
DOIs
StatePublished - Sep 2023

Funding

FundersFunder number
Israel Science Foundation2180/20

    Keywords

    • family wise error
    • most powerful test
    • multiple end-points
    • sample size determination
    • strong control

    Fingerprint

    Dive into the research topics of 'Optimal multiple testing and design in clinical trials'. Together they form a unique fingerprint.

    Cite this