Is inverse probability of censoring weighting a safer choice than per-protocol analysis in clinical trials?

Autor:	Xuan J; MRC Clinical Trials Unit at UCL, University College London, London, UK., Mt-Isa S; Biostatistics and Research Decision Sciences (BARDS) Health Technology Assessment (HTA) Statistics, MSD, Zurich, Switzerland., Latimer N; Sheffield Centre for Health and Related Research, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.; Delta Hat Limited, Nottingham, UK., Bell Gorrod H; Sheffield Centre for Health and Related Research, School of Medicine and Population Health, University of Sheffield, Sheffield, UK., Malbecq W; Department of Mathematics, University of Brussels, Brussels, Belgium.; Former employee of MSD, Brussels, Belgium throughout most of the duration of this study., Vandormael K; Biostatistics and Research Decision Sciences (BARDS) Health Technology Assessment (HTA) Statistics, MSD, Brussels, Belgium., Yorke-Edwards V; MRC Clinical Trials Unit at UCL, University College London, London, UK.; Centre for Advanced Research Computing, University College London, London, UK., White IR; MRC Clinical Trials Unit at UCL, University College London, London, UK.
Jazyk:	angličtina
Zdroj:	Statistical methods in medical research [Stat Methods Med Res] 2024 Dec 12, pp. 9622802241289559. Date of Electronic Publication: 2024 Dec 12.
DOI:	10.1177/09622802241289559
Abstrakt:	Deviation from the treatment strategy under investigation occurs in many clinical trials. We term this intervention deviation. Per-protocol analyses are widely adopted to estimate a hypothetical estimand without the occurrence of intervention deviation. Per-protocol by censoring is prone to selection bias when intervention deviation is associated with time-varying confounders that also influence counterfactual outcomes. This can be corrected by inverse probability of censoring weighting, which gives extra weight to uncensored individuals who had similar prognostic characteristics to censored individuals. Such weights are computed by modelling selected covariates. Inverse probability of censoring weighting relies on the no unmeasured confounding assumption whose plausibility is not statistically testable. Suboptimal implementation of inverse probability of censoring weighting which violates the assumption will lead to bias. In a simulation study, we evaluated the performance of per-protocol and inverse probability of censoring weighting with different implementations to explore whether inverse probability of censoring weighting is a safe alternative to per-protocol. Scenarios were designed to vary intervention deviation in one or both arms with different prevalences, correlation between two confounders, effect of each confounder, and sample size. Results show that inverse probability of censoring weighting with different combinations of covariates outperforms per-protocol in most scenarios, except for an unusual case where selection bias caused by two confounders is in two directions, and 'cancels' out. Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Databáze:	MEDLINE
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