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Optimality of testing procedures for survival data in the nonproportional hazards setting
Author(s) -
Arfè Andrea,
Alexander Brian,
Trippa Lorenzo
Publication year - 2021
Publication title -
biometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.298
H-Index - 130
eISSN - 1541-0420
pISSN - 0006-341X
DOI - 10.1111/biom.13315
Subject(s) - frequentist inference , type i and type ii errors , bayesian probability , statistical hypothesis testing , statistics , benchmark (surveying) , computer science , proportional hazards model , econometrics , mathematics , bayesian inference , geodesy , geography
Most statistical tests for treatment effects used in randomized clinical trials with survival outcomes are based on the proportional hazards assumption, which often fails in practice. Data from early exploratory studies may provide evidence of nonproportional hazards, which can guide the choice of alternative tests in the design of practice‐changing confirmatory trials. We developed a test to detect treatment effects in a late‐stage trial, which accounts for the deviations from proportional hazards suggested by early‐stage data. Conditional on early‐stage data, among all tests that control the frequentist Type I error rate at a fixed α level, our testing procedure maximizes the Bayesian predictive probability that the study will demonstrate the efficacy of the experimental treatment. Hence, the proposed test provides a useful benchmark for other tests commonly used in the presence of nonproportional hazards, for example, weighted log‐rank tests. We illustrate this approach in simulations based on data from a published cancer immunotherapy phase III trial.