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Cited by 189Statistical Methods in Clinical TrialsMeta-analysis and systematic reviewsStatistical Methods and Bayesian Inference

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Discordance between reported intention-to-treat and per protocol analyses

Porta, Núria, Bonet, Catalina, Cobo, Erik·2007·Journal of Clinical Epidemiology
DOI 10.1016/j.jclinepi.2006.09.013
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Abstract

Objective To quantify the degree of disagreement between the two most popular methods for dealing with missing data: intention to treat (ITT) and per protocol (PP). Study design and setting We performed a systematic review of randomized two-armed clinical trials (CTs) published between 2001 and 2003, abstracted in PubMed and reporting both the ITT and PP analyses on a primary binary endpoint, out of which 74 papers were finally selected. The treatment effect of each CT was measured by the odds ratio, and the disagreement between them was quantified by the Bland-Altman method. Results On average, the PP estimator provides greater values Log(e)ORPP=1 x 25.Log(e)ORITT, (95% CI: 1.15, 1.35) than the corresponding ITT estimator, although the limits of concordance showed that the ratio between the two estimators varies greatly from 0.39 up to 2.53. Conclusion These results confirm that missing values may cause both systematic and unpredictable bias in CTs. Further efforts should be made to minimize protocol deviations and to use better statistical methods to highlight the drawbacks of missing information. In the presence of protocol deviations, the conclusion of a CT cannot rest on the single reporting of either the ITT or the PP approach alone.

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Metadata

Authors
Porta, N., Bonet, C., & Cobo, E.
Affiliations
Universitat Politècnica de Catalunya (ES)
Corresponding author
Cobo, Erik
ORCID
Venue
Journal of Clinical Epidemiology
Publisher
Elsevier BV
Published
2007-07
Volume
60
Issue
7
Pages
663-669
ISSN
0895-4356 (ISSN-L)
DOI
10.1016/j.jclinepi.2006.09.013
OpenAlex
W1993417604
Cited by
189
References
7
Citations by year
2026: 6 · 2025: 6 · 2024: 9 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 20 · 2019: 14 · 2018: 8 · 2017: 11 · 2016: 8 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 11
FWCI
10.92
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Clinical Epidemiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Instituto de Salud Carlos III
Topics
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
Keywords
intention-to-treat analysis, per-protocol analysis, missing data, protocol deviations, treatment effect estimation, odds ratio, Bland-Altman agreement
MeSH terms
Systematic Reviews as Topic, Data Interpretation, Statistical, Humans, Periodicals as Topic, Reproducibility of Results, Epidemiologic Research Design, Bias, Randomized Controlled Trials as Topic, Treatment Outcome, Sample Size

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