Meta-analysis combining parallel and cross-over clinical trials. III: The issue of carry-over.
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.
Curtin
François
F
Medical Statistics Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1 7HT, UK. francoiscurtin@compuserve.com
Elbourne
Diana
D
Altman
Douglas G
DG
D001794:Blood Pressure / Q000502:physiology; D002986:Clinical Trials as Topic / Q000379:methods*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D015983:Selection Bias; D012982:Sodium, Dietary; D013223:Statistics as Topic / Q000379:methods*
D012982:Sodium, Dietary