Some problems with the investigation of noninferiority in meta-analysis.
OBJECTIVE
Noninferiority trials have become commonplace in recent years. Like individual clinical trials, meta-analyses can also investigate noninferiority. However, certain important topics have to be considered.


METHODS
The proposed methods in this paper have their origin in the framework of noninferiority trials and meta-analyses. This paper can therefore be seen as a combination of both fields. Two issues are highlighted in the paper; difficulties in the choice of delta for a noninferiority meta-analysis leading to different deltas and methods for meta-analyses with different analysis sets, based on the full-analysis set with the intention-to-treat principle or the per-protocol population. Analytical methods, sensitivity analyses, meta-regression, and a bivariate method are introduced. The proposed graphical presentations support the analytical results.


CONCLUSIONS
The confidence interval approach using meta-regression or bivariate methods is appropriate using both analysis sets for meta-analyses investigating noninferiority.
Witte
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Department of Medical Biometry, University of Heidelberg, Heidelberg, Germany. witte@imbi.uni-heidelberg.de
Victor
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N
D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D015201:Meta-Analysis as Topic; D013223:Statistics as Topic / Q000379:methods*