ArticleClinical trials (London, England)2019
Generalizing the per-protocol treatment effect: The case of ACTG A5095.
Article in Clinical trials (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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.
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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.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Home visits versus fixed-site care by community health workers and child survival: a cluster-randomized trial, Mali.Bulletin of the World Health Organization · 2024Trial
- Toward a Clearer Definition of Selection Bias When Estimating Causal Effects.Epidemiology (Cambridge, Mass.) · 2022Article
- Generalizing trial evidence to target populations in non-nested designs: Applications to AIDS clinical trials.Journal of the Royal Statistical Society. Series C, Applied statistics · 2022Article
- Applicability of Transcatheter Aortic Valve Replacement Trials to Real-World Clinical Practice: Findings From EXTEND-CoreValve.JACC. Cardiovascular interventions · 2021Article
- Clinical Effectiveness of Integrase Strand Transfer Inhibitor-Based Antiretroviral Regimens Among Adults With Human Immunodeficiency Virus: A Collaboration of Cohort Studies in the United States and Canada.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Effect heterogeneity and variable selection for standardizing causal effects to a target population.European journal of epidemiology · 2019Article
- Extending inferences from a randomized trial to a target population.European journal of epidemiology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIntention-to-treat comparisons of randomized trials provide asymptotically consistent estimators of the effect of treatment assignment, without regard to compliance. However, decision makers often wish to know the effect of a per-protocol comparison. Moreover, decision makers may also wish to know the effect of treatment assignment or treatment protocol in a user-specified target population other than the sample in which the trial was fielded. Here, we aimed to generalize results from the ACTG A5095 trial to the US recently HIV-diagnosed target population.
methodsWe first replicated the published conventional intention-to-treat estimate (2-year risk difference and hazard ratio) comparing a four-drug antiretroviral regimen to a three-drug regimen in the A5095 trial. We then estimated the intention-to-treat effect that accounted for informative dropout and the per-protocol effect that additionally accounted for protocol deviations by constructing inverse probability weights. Furthermore, we employed inverse odds of sampling weights to generalize both intention-to-treat and per-protocol effects to a target population comprising US individuals with HIV diagnosed during 2008-2014.
resultsOf 761 subjects in the analysis, 82 dropouts (36 in the three-drug arm and 46 in the four-drug arm) and 59 protocol deviations (25 in the three-drug arm and 34 in the four-drug arm) occurred during the first 2 years of follow-up. A total of 169 subjects incurred virologic failure or death. The 2-year risks were similar both in the trial and in the US HIV-diagnosed target population for estimates from the conventional intention-to-treat, dropout-weighted intention-to-treat, and per-protocol analyses. In the US target population, the 2-year conventional intention-to-treat risk difference (unit: %) for virologic failure or death comparing the four-drug arm to the three-drug arm was -0.4 (95% confidence interval: -6.2, 5.1), while the hazard ratio was 0.97 (95% confidence interval: 0.70, 1.34); the 2-year risk difference was -0.9 (95% confidence interval: -6.9, 5.3) for the dropout-weighted intention-to-treat comparison (hazard ratio = 0.95, 95% confidence interval: 0.68, 1.32) and -0.7 (95% confidence interval: -6.7, 5.5) for the per-protocol comparison (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34).
conclusionNo benefit of four-drug antiretroviral regimen over three-drug regimen was found from the conventional intention-to-treat, dropout-weighted intention-to-treat or per-protocol estimates in the trial sample or target population.
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