Xuan, Jingyi;
Mt-Isa, Shahrul;
Latimer, Nicholas;
Gorrod, Helen;
Malbecq, William;
Vandormael, Kristel;
Yorke-Edwards, Victoria;
(2024)
Is inverse probability of censoring weighting a safer choice than per-protocol analysis in clinical trials?
Statistical Methods in Medical Research
10.1177/09622802241289559.
(In press).
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Is inverse probability of censoring weighting a safer choice than per-protocol analysis in clinical trials? |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1177/09622802241289559 |
| Publisher version: | https://doi.org/10.1177/09622802241289559 |
| Language: | English |
| Additional information: | © The Author(s), 2024. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10201685 |
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