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Discordance between reported intention-to-treat and per protocol analyses
Núria Porta1, Catalina Bonet, Erik Cobo
1Department of Statistics and Operational Research, Universitat Politècnica de Catalunya, Pau Gargallo 5, 08028 - Barcelona, Spain.
Journal of Clinical Epidemiology
|June 19, 2007
Summary
Disagreement between intention to treat (ITT) and per protocol (PP) analyses in clinical trials is significant. Missing data can cause unpredictable bias, necessitating careful statistical methods and minimizing protocol deviations.
Area of Science:
- Biostatistics
- Clinical Trial Methodology
Background:
- Missing data is a common challenge in clinical trials.
- Intention to treat (ITT) and per protocol (PP) are widely used methods for handling missing data.
Purpose of the Study:
- To quantify the disagreement between ITT and PP methods for handling missing data.
- To assess the impact of missing data on clinical trial results.
Main Methods:
- Systematic review of randomized two-armed clinical trials (2001-2003).
- Abstracted PubMed data reporting both ITT and PP analyses.
- Quantified treatment effect using odds ratio and disagreement using Bland-Altman method.
Main Results:
- Per protocol (PP) estimators were, on average, higher than intention to treat (ITT) estimators (Log(e)OR = 1.25, 95% CI: 1.15, 1.35).
- The ratio between PP and ITT estimators varied widely (0.39 to 2.53), indicating substantial disagreement.
Conclusions:
- Missing data can introduce systematic and unpredictable bias in clinical trials.
- Minimizing protocol deviations and employing robust statistical methods are crucial.
- Clinical trial conclusions should not rely solely on ITT or PP analysis when protocol deviations exist.
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