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Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study
Objective To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Design Meta-epidemiological study. Data sources Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 31...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group Ltd.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445790/ https://www.ncbi.nlm.nih.gov/pubmed/26016488 http://dx.doi.org/10.1136/bmj.h2445 |
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author | Abraha, Iosief Cherubini, Antonio Cozzolino, Francesco De Florio, Rita Luchetta, Maria Laura Rimland, Joseph M Folletti, Ilenia Marchesi, Mauro Germani, Antonella Orso, Massimiliano Eusebi, Paolo Montedori, Alessandro |
author_facet | Abraha, Iosief Cherubini, Antonio Cozzolino, Francesco De Florio, Rita Luchetta, Maria Laura Rimland, Joseph M Folletti, Ilenia Marchesi, Mauro Germani, Antonella Orso, Massimiliano Eusebi, Paolo Montedori, Alessandro |
author_sort | Abraha, Iosief |
collection | PubMed |
description | Objective To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Design Meta-epidemiological study. Data sources Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. Eligibility criteria for selecting studies From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value <1 indicated larger treatment effects in mITT trials than in other trial categories). Results 50 meta-analyses and 322 comparisons of randomised trials (from 84 ITT trials, 118 mITT trials, and 108 no ITT trials; 12 trials contributed twice to the analysis) were examined. Compared with ITT trials, mITT trials showed a larger intervention effect (pooled ratio of odds ratios 0.83 (95% confidence interval 0.71 to 0.96), P=0.01; between meta-analyses variance τ(2)=0.13). Adjustments for sample size, type of centre, funding, items of risk of bias, post-randomisation exclusions, and variance of log odds ratio yielded consistent results (0.80 (0.69 to 0.94), P=0.005; τ(2)=0.08). After exclusion of five influential studies, results remained consistent (0.85 (0.75 to 0.98); τ(2)=0.08). The comparison between mITT trials and no ITT trials showed no statistical difference between the two groups (adjusted ratio of odds ratios 0.92 (0.70 to 1.23); τ(2)=0.57). Conclusions Trials that deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations. |
format | Online Article Text |
id | pubmed-4445790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BMJ Publishing Group Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-44457902015-05-28 Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study Abraha, Iosief Cherubini, Antonio Cozzolino, Francesco De Florio, Rita Luchetta, Maria Laura Rimland, Joseph M Folletti, Ilenia Marchesi, Mauro Germani, Antonella Orso, Massimiliano Eusebi, Paolo Montedori, Alessandro BMJ Research Objective To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Design Meta-epidemiological study. Data sources Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. Eligibility criteria for selecting studies From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value <1 indicated larger treatment effects in mITT trials than in other trial categories). Results 50 meta-analyses and 322 comparisons of randomised trials (from 84 ITT trials, 118 mITT trials, and 108 no ITT trials; 12 trials contributed twice to the analysis) were examined. Compared with ITT trials, mITT trials showed a larger intervention effect (pooled ratio of odds ratios 0.83 (95% confidence interval 0.71 to 0.96), P=0.01; between meta-analyses variance τ(2)=0.13). Adjustments for sample size, type of centre, funding, items of risk of bias, post-randomisation exclusions, and variance of log odds ratio yielded consistent results (0.80 (0.69 to 0.94), P=0.005; τ(2)=0.08). After exclusion of five influential studies, results remained consistent (0.85 (0.75 to 0.98); τ(2)=0.08). The comparison between mITT trials and no ITT trials showed no statistical difference between the two groups (adjusted ratio of odds ratios 0.92 (0.70 to 1.23); τ(2)=0.57). Conclusions Trials that deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations. BMJ Publishing Group Ltd. 2015-05-27 /pmc/articles/PMC4445790/ /pubmed/26016488 http://dx.doi.org/10.1136/bmj.h2445 Text en © Abraha et al 2015 http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Abraha, Iosief Cherubini, Antonio Cozzolino, Francesco De Florio, Rita Luchetta, Maria Laura Rimland, Joseph M Folletti, Ilenia Marchesi, Mauro Germani, Antonella Orso, Massimiliano Eusebi, Paolo Montedori, Alessandro Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study |
title | Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study |
title_full | Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study |
title_fullStr | Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study |
title_full_unstemmed | Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study |
title_short | Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study |
title_sort | deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445790/ https://www.ncbi.nlm.nih.gov/pubmed/26016488 http://dx.doi.org/10.1136/bmj.h2445 |
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