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Main Authors: Tong, Jiaqi, Cheng, Chao, Tong, Guangyu, Harhay, Michael O., Li, Fan
Format: Preprint
Published: 2024
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Online Access:https://arxiv.org/abs/2410.07483
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author Tong, Jiaqi
Cheng, Chao
Tong, Guangyu
Harhay, Michael O.
Li, Fan
author_facet Tong, Jiaqi
Cheng, Chao
Tong, Guangyu
Harhay, Michael O.
Li, Fan
contents In clinical trials, the observation of participant outcomes may frequently be hindered by death, leading to ambiguity in defining a scientifically meaningful final outcome for those who die. Principal stratification methods are valuable tools for addressing the average causal effect among always-survivors, i.e., the average treatment effect among a subpopulation defined as those who would survive regardless of treatment assignment. Although robust methods for the truncation-by-death problem in two-arm clinical trials have been previously studied, its expansion to multi-arm clinical trials remains elusive. In this article, we study the identification of a class of survivor average causal effect estimands with multiple treatments under monotonicity and principal ignorability, and first propose simple weighting and regression approaches for point estimation. As a further improvement, we derive the efficient influence function to motivate doubly robust estimators for the survivor average causal effects in multi-arm clinical trials. We also propose sensitivity methods under violations of key causal assumptions. Extensive simulations are conducted to investigate the finite-sample performance of the proposed methods against the existing methods, and a real data example is used to illustrate how to operationalize the proposed estimators and the sensitivity methods in practice.
format Preprint
id arxiv_https___arxiv_org_abs_2410_07483
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Doubly robust estimation and sensitivity analysis with outcomes truncated by death in multi-arm clinical trials
Tong, Jiaqi
Cheng, Chao
Tong, Guangyu
Harhay, Michael O.
Li, Fan
Methodology
In clinical trials, the observation of participant outcomes may frequently be hindered by death, leading to ambiguity in defining a scientifically meaningful final outcome for those who die. Principal stratification methods are valuable tools for addressing the average causal effect among always-survivors, i.e., the average treatment effect among a subpopulation defined as those who would survive regardless of treatment assignment. Although robust methods for the truncation-by-death problem in two-arm clinical trials have been previously studied, its expansion to multi-arm clinical trials remains elusive. In this article, we study the identification of a class of survivor average causal effect estimands with multiple treatments under monotonicity and principal ignorability, and first propose simple weighting and regression approaches for point estimation. As a further improvement, we derive the efficient influence function to motivate doubly robust estimators for the survivor average causal effects in multi-arm clinical trials. We also propose sensitivity methods under violations of key causal assumptions. Extensive simulations are conducted to investigate the finite-sample performance of the proposed methods against the existing methods, and a real data example is used to illustrate how to operationalize the proposed estimators and the sensitivity methods in practice.
title Doubly robust estimation and sensitivity analysis with outcomes truncated by death in multi-arm clinical trials
topic Methodology
url https://arxiv.org/abs/2410.07483