Causal inference with outcomes truncated by death in multiarm studies

It is challenging to evaluate causal effects when the outcomes of interest suffer from truncation‐by‐death in many clinical studies; that is, outcomes cannot be observed if patients die before the time of measurement. To address this problem, it is common to consider average treatment effects by pri...

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Veröffentlicht in:Biometrics 2023-03, Vol.79 (1), p.502-513
Hauptverfasser: Luo, Shanshan, Li, Wei, He, Yangbo
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Li, Wei
He, Yangbo
description It is challenging to evaluate causal effects when the outcomes of interest suffer from truncation‐by‐death in many clinical studies; that is, outcomes cannot be observed if patients die before the time of measurement. To address this problem, it is common to consider average treatment effects by principal stratification, for which, the identifiability results and estimation methods with a binary treatment have been established in previous literature. However, in multiarm studies with more than two treatment options, estimation of causal effects becomes more complicated and requires additional techniques. In this article, we consider identification, estimation, and bounds of causal effects with multivalued ordinal treatments and the outcomes subject to truncation‐by‐death. We define causal parameters of interest in this setting and show that they are identifiable either using some auxiliary variable or based on linear model assumption. We then propose a semiparametric method for estimating the causal parameters and derive their asymptotic results. When the identification conditions are invalid, we derive sharp bounds of the causal effects by use of covariates adjustment. Simulation studies show good performance of the proposed estimator. We use the estimator to analyze the effects of a four‐level chronic toxin on fetal developmental outcomes such as birth weight in rats and mice, with data from a developmental toxicity trial conducted by the National Toxicology Program. Data analyses demonstrate that a high dose of the toxin significantly reduces the weights of pups.
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To address this problem, it is common to consider average treatment effects by principal stratification, for which, the identifiability results and estimation methods with a binary treatment have been established in previous literature. However, in multiarm studies with more than two treatment options, estimation of causal effects becomes more complicated and requires additional techniques. In this article, we consider identification, estimation, and bounds of causal effects with multivalued ordinal treatments and the outcomes subject to truncation‐by‐death. We define causal parameters of interest in this setting and show that they are identifiable either using some auxiliary variable or based on linear model assumption. We then propose a semiparametric method for estimating the causal parameters and derive their asymptotic results. When the identification conditions are invalid, we derive sharp bounds of the causal effects by use of covariates adjustment. Simulation studies show good performance of the proposed estimator. We use the estimator to analyze the effects of a four‐level chronic toxin on fetal developmental outcomes such as birth weight in rats and mice, with data from a developmental toxicity trial conducted by the National Toxicology Program. Data analyses demonstrate that a high dose of the toxin significantly reduces the weights of pups.</description><identifier>ISSN: 0006-341X</identifier><identifier>EISSN: 1541-0420</identifier><identifier>DOI: 10.1111/biom.13554</identifier><identifier>PMID: 34435657</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Asymptotic methods ; Birth weight ; bounds ; Causality ; Computer Simulation ; Death ; Death &amp; dying ; developmental toxicity ; Estimation ; Fetuses ; Mice ; Models, Statistical ; multiarm study ; Parameter identification ; Rats ; Toxicity ; Toxicology ; truncation‐by‐death</subject><ispartof>Biometrics, 2023-03, Vol.79 (1), p.502-513</ispartof><rights>2021 The International Biometric Society.</rights><rights>2023 The International Biometric Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3164-751f4ed663a93015b1141a6c798638d0f352e6e830f15ed2579f95b08e186b183</cites><orcidid>0000-0003-2461-2522</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbiom.13554$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbiom.13554$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34435657$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Shanshan</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>He, Yangbo</creatorcontrib><title>Causal inference with outcomes truncated by death in multiarm studies</title><title>Biometrics</title><addtitle>Biometrics</addtitle><description>It is challenging to evaluate causal effects when the outcomes of interest suffer from truncation‐by‐death in many clinical studies; that is, outcomes cannot be observed if patients die before the time of measurement. 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subjects Animals
Asymptotic methods
Birth weight
bounds
Causality
Computer Simulation
Death
Death & dying
developmental toxicity
Estimation
Fetuses
Mice
Models, Statistical
multiarm study
Parameter identification
Rats
Toxicity
Toxicology
truncation‐by‐death
title Causal inference with outcomes truncated by death in multiarm studies
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