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Statistics in Medicine
Article . 2024 . Peer-reviewed
License: CC BY
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zbMATH Open
Article . 2024
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Two‐stage randomized clinical trials with a right‐censored endpoint: Comparison of frequentist and Bayesian adaptive designs

Two-stage randomized clinical trials with a right-censored endpoint: comparison of frequentist and Bayesian adaptive designs
Authors: Luana Boumendil; Sylvie Chevret; Vincent Lévy; Lucie Biard;

Two‐stage randomized clinical trials with a right‐censored endpoint: Comparison of frequentist and Bayesian adaptive designs

Abstract

Adaptive randomized clinical trials are of major interest when dealing with a time‐to‐event outcome in a prolonged observation window. No consensus exists either to define stopping boundaries or to combine values or test statistics in the terminal analysis in the case of a frequentist design and sample size adaptation. In a one‐sided setting, we compared three frequentist approaches using stopping boundaries relying on ‐spending functions and a Bayesian monitoring setting with boundaries based on the posterior distribution of the log‐hazard ratio. All designs comprised a single interim analysis with an efficacy stopping rule and the possibility of sample size adaptation at this interim step. Three frequentist approaches were defined based on the terminal analysis: combination of stagewise statistics (Wassmer) or of values (Desseaux), or on patientwise splitting (Jörgens), and we compared the results with those of the Bayesian monitoring approach (Freedman). These different approaches were evaluated in a simulation study and then illustrated on a real dataset from a randomized clinical trial conducted in elderly patients with chronic lymphocytic leukemia. All approaches controlled for the type I error rate, except for the Bayesian monitoring approach, and yielded satisfactory power. It appears that the frequentist approaches are the best in underpowered trials. The power of all the approaches was affected by the violation of the proportional hazards (PH) assumption. For adaptive designs with a survival endpoint and a one‐sided alternative hypothesis, the Wassmer and Jörgens approaches after sample size adaptation should be preferred, unless violation of PH is suspected.

Keywords

combination test, Models, Statistical, Endpoint Determination, Bayesian boundaries, Bayes Theorem, interim analysis, Leukemia, Lymphocytic, Chronic, B-Cell, Applications of statistics to biology and medical sciences; meta analysis, survival trial, Research Design, Sample Size, adaptive design, Humans, Computer Simulation, Randomized Controlled Trials as Topic

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
hybrid
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