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Published on: September 20, 2019
Nonadherence to treatment protocol in published randomised controlled trials: a review
Susanna Dodd1, Ian R White, Paula Williamson
1Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GS, UK. s.r.dodd@liv.ac.uk
Trials
|June 20, 2012
Summary
Reporting of nonadherence to treatment protocol in randomized controlled trials (RCTs) is often incomplete. While statistical methods are used, their application and the definition of analysis populations for benefits and harms require improvement to avoid bias.
Area of Science:
- Clinical Trials Methodology
- Biostatistics
- Evidence-Based Medicine
Background:
- Nonadherence to treatment protocols is common in randomized controlled trials (RCTs).
- Inadequate reporting and analysis of nonadherence can impact the reliability of trial results.
- Existing methods for addressing nonadherence may not fully account for potential biases.
Purpose of the Study:
- To assess the reporting and statistical handling of nonadherence to treatment protocols in published RCTs.
- To evaluate the quality of reporting for treatment initiation, adherence, and statistical analyses of nonadherence.
- To identify gaps in the analysis of nonadherence and its impact on benefit and harm outcomes.
Main Methods:
- A random sample of 100 RCT publications from high-impact journals in 2008 was reviewed.
- Data extraction focused on the reporting of nonadherence, statistical methods used, and definition of analysis populations.
- Quality assessment of reporting for nonadherence and statistical methods was performed.
Main Results:
- Nonadherence was reported in 98% of trials, but reporting was often vague or incomplete.
- Treatment initiation and completeness reporting was inadequate in 64% (short-term) and 89% (long-term) of trials.
- Over half of trials used statistical methods for nonadherence, primarily per-protocol analysis, but definitions of analysis sets were often unclear, especially for harms outcomes.
Conclusions:
- Adherence to randomized interventions is poorly addressed in RCT reporting and analysis.
- Current statistical approaches to nonadherence often fail to adequately consider introduced bias.
- Improved methods and guidance are needed for causal adjustment and appropriate analysis populations in the presence of nonadherence.
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