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

Daxuan Deng, Vernon M. Chinchilli, Hao Feng, Chixiang Chen, Ming Wang

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
JournalStatistical Methods in Medical Research
StateAccepted/In press - 2024

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Statistics and Probability
  • Health Information Management

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