Regulatory Experiences with the Use of Multiple Imputation for Missing Data in a Phase 3 Confirmatory Trial.

ABSTRACT: The Mixed Model for Repeated Measures (MMRM) is widely used in clinical trials, however, its reliance on the Missing at Random (MAR) assumption and the exclusion of subjects lacking post-baseline data have been points of scrutiny, particularly due to misalignment with the Intent-to-Treat (ITT) principle. This paper presents an application of Multiple Imputation (MI) to address missing data in a hypertension clinical trial and discusses the subsequent interactions with regulatory authorities requesting additional analyses predominantly based on a Missing not at Random (MNAR) assumption. While MNAR-based approaches have been traditionally used for sensitivity analyses, we present an example demonstrating that regulatory agencies are increasingly expecting their integration into primary analy

SUBMITTER: Sassi-Sayadi M 

PROVIDER: S-EPMC12753554 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature