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Meta‐analysis combining parallel and cross‐over clinical trials. III: The issue of carry‐over
Author(s) -
Curtin François,
Elbourne Diana,
Altman Douglas G.
Publication year - 2002
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.1207
Subject(s) - pooling , estimator , carry (investment) , statistics , meta analysis , computer science , cross over , cross validation , econometrics , mathematics , medicine , artificial intelligence , finance , economics
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. Copyright © 2002 John Wiley & Sons, Ltd.