SynthesisBMJ open2022
Statistical methods for non-adherence in non-inferiority trials: useful and used? A systematic review.
Synthesis in BMJ open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of simulation studies which compare existing statistical methods to account for non-compliance in randomised controlled trials.BMC medical research methodology · 2023Pooled it
- Clinical equivalence and non-inferiority within health technology assessment.The European journal of health economics : HEPAC : health economics in prevention and care · 2026Article
- Applying the Estimands Framework to Non-Inferiority Trials: Guidance on Choice of Hypothetical Estimands for Non-Adherence and Comparison of Estimation Methods.Statistics in medicine · 2025Article
- Protocol for visual-acoustic intervention with service delivery in-person and via telepractice (VISIT) non-inferiority trial for residual speech sound disorder.BMC pediatrics · 2025Article
- Estimating the Effect of a Treatment When There Is Nonadherence in a Trial.American journal of epidemiology · 2023Article
- Understanding Study Drug Discontinuation Through EUCLID.Frontiers in cardiovascular medicine · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
backgroundIn non-inferiority trials with non-adherence to interventions (or non-compliance), intention-to-treat and per-protocol analyses are often performed; however, non-random non-adherence generally biases these estimates of efficacy.
objectiveTo identify statistical methods that adjust for the impact of non-adherence and thus estimate the causal effects of experimental interventions in non-inferiority trials.
designA systematic review was conducted by searching the Ovid MEDLINE database (31 December 2020) to identify (1) randomised trials with a primary analysis for non-inferiority that applied (or planned to apply) statistical methods to account for the impact of non-adherence to interventions, and (2) methodology papers that described such statistical methods and included a non-inferiority trial application. OUTCOMES: The statistical methods identified, their impacts on non-inferiority conclusions, and their advantages/disadvantages.
resultsA total of 24 papers were included (4 protocols, 13 results papers and 7 methodology papers) reporting relevant methods on 26 occasions. The most common were instrumental variable approaches (n=9), including observed adherence as a covariate within a regression model (n=3), and modelling adherence as a time-varying covariate in a time-to-event analysis (n=3). Other methods included rank preserving structural failure time models and inverse-probability-of-treatment weighting. The methods identified in protocols and results papers were more commonly specified as sensitivity analyses (n=13) than primary analyses (n=3). Twelve results papers included an alternative analysis of the same outcome; conclusions regarding non-inferiority were in agreement on six occasions and could not be compared on six occasions (different measures of effect or results not provided in full).
conclusionsAvailable statistical methods which attempt to account for the impact of non-adherence to interventions were used infrequently. Therefore, firm inferences about their influence on non-inferiority conclusions could not be drawn. Since intention-to-treat and per-protocol analyses do not guarantee unbiased conclusions regarding non-inferiority, the methods identified should be considered for use in sensitivity analyses. PROSPERO REGISTRATION NUMBER: CRD42020177458.
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Registered trials
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