Cited by 111Advanced Causal Inference TechniquesStatistical Methods in Clinical TrialsStatistical Methods and Bayesian Inference

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A Comparison of Methods for Estimating the Causal Effect of a Treatment in Randomized Clinical Trials Subject to Noncompliance

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Little, Roderick J., Long, Qi, Lin, Xihong·2009·Biometrics

DOI 10.1111/j.1541-0420.2008.01066.x

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Abstract

Summary We consider the analysis of clinical trials that involve randomization to an active treatment (T = 1) or a control treatment (T = 0), when the active treatment is subject to all‐or‐nothing compliance. We compare three approaches to estimating treatment efficacy in this situation: as‐treated analysis, per‐protocol analysis, and instrumental variable (IV) estimation, where the treatment effect is estimated using the randomization indicator as an IV. Both model‐ and method‐of‐moment based IV estimators are considered. The assumptions underlying these estimators are assessed, standard errors and mean squared errors of the estimates are compared, and design implications of the three methods are examined. Extensions of the methods to include observed covariates are then discussed, emphasizing the role of compliance propensity methods and the contrasting role of covariates in these extensions. Methods are illustrated on data from the Women Take Pride study, an assessment of behavioral treatments for women with heart disease.

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Authors: Little, R. J., Long, Q., & Lin, X.
Affiliations: University of Michigan (US)
Emory University (US)
Harvard University (US)
Corresponding author: Little, Roderick J.
Long, Qi
Lin, Xihong
ORCID: Little, Roderick J.
Long, Qi
Lin, Xihong
Venue: Biometrics
Publisher: Oxford University Press (OUP)
Published: 2009-05-28
Volume: 65
Issue: 2
Pages: 640-649
ISSN: 0006-341X (ISSN-L)
1541-0420
DOI: 10.1111/j.1541-0420.2008.01066.x
OpenAlex: W2144385713
Cited by: 111
References: 34
Citations by year: 2026: 5 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 11 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 8
FWCI: 5.95
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Biometrics (publishedVersion)
PubMed (publishedVersion)
Deep Blue (University of Michigan) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Collection of Biostatistics Research Archive (submittedVersion)
Funders: National Cancer Institute (R01CA076404)
Topics: Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
Keywords: treatment non-adherence, causal effect estimation, randomized controlled trials, as-treated analysis, per-protocol analysis, instrumental variable estimation
MeSH terms: Algorithms, Biometry, Computer Simulation, Data Interpretation, Statistical, Patient Compliance, Models, Statistical, Epidemiologic Research Design, Causality, Proportional Hazards Models, Randomized Controlled Trials as Topic, Outcome Assessment, Health Care

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A Comparison of Methods for Estimating the Causal Effect of a Treatment in Randomized Clinical Trials Subject to Noncompliance

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