Robust integration of secondary outcomes information into primary outcome analysis in the presence of missing data

In clinical and observational studies, secondary outcomes are frequently collected alongside the primary outcome for each subject, yet their potential to improve the analysis efficiency remains underutilized. Moreover, missing data, commonly encountered in practice, can introduce bias to estimates if not appropriately addressed. This article presents an innovative approach that enhances the empirical likelihood-based information borrowing method by integrating missing-data techniques, ensuring robust data integration. We introduce a plug-in inverse probability weighting estimator to handle missingness in the primary analysis, demonstrating its equivalence to the standard joint estimator under mild conditions. To address potential bias from missing secondary outcomes, we propose a uniform mapping strategy, imputing incomplete secondary outcomes into a unified space. Extensive simulations highlight the effectiveness of our method, showing consistent, efficient, and robust estimators under various scenarios involving missing data and/or misspecified secondary models. Finally, we apply our proposal to the Uniform Data Set from the National Alzheimer’s Coordinating Center, exemplifying its practical application.

Daxuan Deng et al, Robust integration of secondary outcomes information into primary outcome analysis in the presence of missing data, Statistical Methods in Medical Research (33, 7) pp. 1249-1263. Copyright © 2024. DOI: 10.1177/09622802241254195. Users who receive access to an article through a repository are reminded that the article is protected by copyright and reuse is restricted to non-commercial and no derivative uses. Users may also download and save a local copy of an article accessed in an institutional repository for the user's personal reference. For permission to reuse an article, please follow our Process for Requesting Permission.