ArticleClinical trials (London, England)2016
Adherence adjustment in the Coronary Drug Project: A call for better per-protocol effect estimates in randomized trials.
Article in Clinical trials (London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03672630 (Comparison of Two- Versus Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease), which is not on this map. Cited by 29 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Comparison of Two- Versus Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease
Who cites it
29 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Statistical Methods for Adjusting Estimates of Treatment Effectiveness for Patient Nonadherence in the Context of Time-to-Event Outcomes and Health Technology Assessment: A Systematic Review of Methodological Papers.Medical decision making : an international journal of the Society for Medical Decision Making · 2019Pooled it
- Patients and investigators prefer measures of absolute risk in subgroups for pragmatic randomized trials.Journal of clinical epidemiology · 2018Pooled it
- Reporting non-adherence in cluster randomised trials: A systematic review.Clinical trials (London, England) · 2018Pooled it
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- The per-protocol effect of immediate versus deferred antiretroviral therapy initiation.AIDS (London, England) · 2016Trial
- Statin Initiation and Mortality After Colorectal Cancer Treatment.JAMA network open · 2026Article
- The effect of long-term adherence to physical activity recommendations in midlife on plasma proteins associated with frailty in the Atherosclerosis Risk in Communities (ARIC) study.European journal of epidemiology · 2026Article
- Advancing efficacy prediction for electronic health records based emulated trials in repurposing heart failure therapies.NPJ digital medicine · 2025Article
- Can algorithms replace expert knowledge for causal inference? A case study on novice use of causal discovery.American journal of epidemiology · 2025Article
- Addressing treatment switching in the ALTA-1L trial with g-methods: exploring the impact of model specification.BMC medical research methodology · 2024Article
- Reply to TaitoAmerican journal of respiratory and critical care medicine · 2024Article
- Synthesizing Subject-matter Expertise for Variable Selection in Causal Effect Estimation: A Case Study.Epidemiology (Cambridge, Mass.) · 2024Article
- [Comparing the effectiveness of multiple dynamic treatment strategies using target trial emulation].Pravention und Gesundheitsforderung · 2023Article
- Estimation of the Average Causal Effect in Longitudinal Data With Time-Varying Exposures: The Challenge of Nonpositivity and the Impact of Model Flexibility.American journal of epidemiology · 2022Article
- Contextualizing single-arm trials with real-world data: An emulated target trial comparing therapies for neovascular age-related macular degeneration.Clinical and translational science · 2021Article
- Article
- Adjusting for adherence in randomized trials when adherence is measured as a continuous variable: An application to the Lipid Research Clinics Coronary Primary Prevention Trial.Clinical trials (London, England) · 2020Article
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Abstract
backgroundIn many randomized controlled trials, patients and doctors are more interested in the per-protocol effect than in the intention-to-treat effect. However, valid estimation of the per-protocol effect generally requires adjustment for prognostic factors associated with adherence. These adherence adjustments have been strongly questioned in the clinical trials community, especially after 1980 when the Coronary Drug Project team found that adherers to placebo had lower 5-year mortality than non-adherers to placebo.
methodsWe replicated the original Coronary Drug Project findings from 1980 and re-analyzed the Coronary Drug Project data using technical and conceptual developments that have become established since 1980. Specifically, we used logistic models for binary outcomes, decoupled the definition of adherence from loss to follow-up, and adjusted for pre-randomization covariates via standardization and for post-randomization covariates via inverse probability weighting.
resultsThe original Coronary Drug Project analysis reported a difference in 5-year mortality between adherers and non-adherers in the placebo arm of 9.4 percentage points. Using modern approaches, we found that this difference was reduced to 2.5 (95% confidence interval: -2.1 to 7.0).
conclusionValid estimation of per-protocol effects may be possible in randomized clinical trials when analysts use appropriate methods to adjust for post-randomization variables.
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