Familywise error control in multi-armed response-adaptive trials

DOI10.1111/BIOM.13042MaRDI QIDQ5214563zbMATH OpenOpenAlexWikidataFDO

Authors David S. Robertson, James Wason

Publication date 7 February 2020

Published in Biometrics (Search for Journal in Brave)

Copyright license Creative Commons Attribution 4.0 International

Full work available at URL https://arxiv.org/abs/1803.05384

zbMATH Keywords

Bayesian methodsclosed testingmultiple comparisonsresponse-adaptive randomizationtype I error

Mathematics Subject Classification ID

Paired and multiple comparisons; multiple testing (62J15) Response surface designs (62K20) Applications of statistics to biology and medical sciences; meta analysis (62P10)

Abstract: Response-adaptive designs allow the randomization probabilities to change during the course of a trial based on cumulated response data, so that a greater proportion of patients can be allocated to the better performing treatments. A major concern over the use of response-adaptive designs in practice, particularly from a regulatory viewpoint, is controlling the type I error rate. In particular, we show that the naive z-test can have an inflated type I error rate even after applying a Bonferroni correction. Simulation studies have often been used to demonstrate error control, but do not provide a guarantee. In this paper, we present adaptive testing procedures for normally distributed outcomes that ensure strong familywise error control, by iteratively applying the conditional invariance principle. Our approach can be used for fully sequential and block randomized trials, and for a large class of adaptive randomization rules found in the literature. We show there is a high price to pay in terms of power to guarantee familywise error control for randomization schemes with extreme allocation probabilities. However, for proposed Bayesian adaptive randomization schemes in the literature, our adaptive tests maintain or increase the power of the trial compared to the z-test. We illustrate our method using a three-armed trial in primary hypercholesterolemia.

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Cited in

(11)

• Type I error for a chi-square test when the response probability changes during a trial
• Multiplicity- and dependency-adjusted p-values for control of the family-wise error rate
• Adaptive transmission disequilibrium test for family trio design
• Maximum type 1 error rate inflation in multiarmed clinical trials with adaptive interim sample size modifications
• Adaptive dose-finding: Proof of concept with type I error control
• Group sequential crossover trial designs with strong control of the familywise error rate
• Probabilistic foundation of confirmatory adaptive designs
• Using randomization tests to preserve type I error with response adaptive and covariate adaptive randomization
• BAGS: a Bayesian adaptive group sequential trial design with subgroup-specific survival comparisons
• Response-adaptive randomization in clinical trials: from myths to practical considerations
• Point estimation for adaptive trial designs. I: A methodological review

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