Meta-analysis of clinical trials with rare events.
Meta-analysis of rare event studies has recently become a subject of controversy and debate. We will argue and demonstrate in this paper that the occurrence of zero events in clinical trials or cohort studies, even if zeros occur in both arms (the case of a double-zero trial), is less problematic, at least from a statistical perspective, if the available statistical tools are applied in the appropriate way. In particular, it is neither necessary nor advisable to exclude studies with zero events from the meta-analysis. In terms of statistical tools, we will focus here on Mantel-Haenszel techniques, mixed Poisson regression and related regression models.
Southampton Statistical Sciences Research Institute & Mathematical Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Dankmar
D
Böhning
Southampton Statistical Sciences Research Institute & Mathematical Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Kalliopi
K
Mylona
Southampton Statistical Sciences Research Institute & Mathematical Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Alan
A
Kimber
D001699:Biometry / Q000379:methods*; D002986:Clinical Trials as Topic; D006801:Humans; D016012:Poisson Distribution; D012044:Regression Analysis
Mantel-Haenszel estimation; Meta-analysis; Poisson regression with random effects; Rare event analysis; Zero and double-zero studies