Meta-analysis combining parallel and cross-over clinical trials. III: The issue of carry-over

Curtin, F; Elbourne, D; Altman, DG; (2002) Meta-analysis combining parallel and cross-over clinical trials. III: The issue of carry-over. Statistics in medicine, 21 (15). pp. 2161-73. ISSN 0277-6715 DOI:

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In meta-analysis combining results from parallel and cross-over trials, there is a risk of bias originating from the carry-over effect in cross-over trials. When pooling treatment effects estimated from parallel trials and two-period two-treatment cross-over trials, meta-analytic estimators of treatment effect can be obtained from the combination of parallel trial results either with cross-over trial results based on data of the first period only or with cross-over trial results analysed with data from both periods. Taking data from the first cross-over period protects against carry-over but gives less efficient treatment estimators and may lead to selection bias. This study evaluates in terms of variance reduction and mean square error the cost of calculating meta-analysis estimates with data from the first period instead of data from the two cross-over periods. If the information on cross-over sequence is available, we recommend performing two combined design meta-analyses, one using the first cross-over period data and one based on data from both cross-over periods. To investigate simultaneously the statistical significance of these two estimators as well as the carry-over at meta-analysis level, a method based on a multivariate analysis of the meta-analytic treatment effect and carry-over estimates is proposed.

Item Type: Article
Keywords: Blood Pressure/physiology, Clinical Trials/*methods, *Cross-Over Studies, Female, Human, Male, *Meta-Analysis, Selection Bias, Sodium, Dietary, Statistics/*methods, Support, Non-U.S. Gov't, Blood Pressure, physiology, Clinical Trials, methods, Cross-Over Studies, Female, Human, Male, Meta-Analysis, Selection Bias, Sodium, Dietary, Statistics, methods, Support, Non-U.S. Gov't
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Medical Statistics
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 12210631
Web of Science ID: 177051300003


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