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Guido Skipka

Publications and source records attributed to Guido Skipka.

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Edgington's Combination Method for Two-Study Meta-Analysis: An Empirical Evaluation in 1226 Meta-Analyses

Two-study meta-analyses are common in evidence synthesis but pose major statistical challenges. With only two studies, the between-study variance cannot be reliably estimated, rendering standard random-effects methods unstable. Here, we investigate meta-analyses based on Edgington's p-value combination method as an alternative approach, applying it to 1226 two-study meta-analyses from the German Institute for Quality and Efficiency in Health Care (IQWiG). Like fixed-effect meta-analysis, Edgington's method is calibrated under homogeneity. However, it adapts confidence interval width to observed between-study discrepancy without requiring explicit heterogeneity estimation. In all of the examined meta-analyses, this leads to confidence intervals that contain both study-specific estimates but remain informative. Edgington's method agrees with fixed-effect meta-analysis on statistical significance (at two-sided $\alpha$ = 0.05) in 91% of all meta-analyses, but can give wider intervals when study results are discrepant and narrower intervals when results are highly consistent. Weighted extensions of Edgington's method shift point estimates toward the more precise study while preserving much of this adaptive behavior. We conclude that Edgington's method offers a principled and practically useful complement to existing approaches for two-study meta-analysis, occupying a middle ground between standard fixed-effect and random-effects approaches.

stat.AP

On estimands and the analysis of adverse events in the presence of varying follow-up times within the benefit assessment of therapies

The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit-risk ratio. The statistical analysis of AEs is complicated by the fact that the follow-up times can vary between the patients included in a clinical trial. This paper takes as its focus the analysis of AE data in the presence of varying follow-up times within the benefit assessment of therapeutic interventions. Instead of approaching this issue directly and solely from an analysis point of view, we first discuss what should be estimated in the context of safety data, leading to the concept of estimands. Although the current discussion on estimands is mainly related to efficacy evaluation, the concept is applicable to safety endpoints as well. Within the framework of estimands, we present statistical methods for analysing AEs with the focus being on the time to the occurrence of the first AE of a specific type. We give recommendations which estimators should be used for the estimands described. Furthermore, we state practical implications of the analysis of AEs in clinical trials and give an overview of examples across different indications. We also provide a review of current practices of health technology assessment (HTA) agencies with respect to the evaluation of safety data. Finally, we describe problems with meta-analyses of AE data and sketch possible solutions.

stat.OT