Handling intercurrent events and missing data in non-inferiority trials using the estimand framework: A tuberculosis case study.

ABSTRACT:

Introduction

The ICH E9 addendum outlining the estimand framework for clinical trials was published in 2019 but provides limited guidance around how to handle intercurrent events for non-inferiority studies. Once an estimand is defined, it is also unclear how to deal with missing values using principled analyses for non-inferiority studies.

Methods

Using a tuberculosis clinical trial as a case study, we propose a primary estimand, and an additional estimand suitable for non-inferiority studies. For estimation, multiple imputation methods that align with the estimands for both primary and sensitivity analysis are proposed. We demonstrate estimation methods using the twofold fully conditional specification multiple imputation algorithm and then extend and use reference-based m

SUBMITTER: Rehal S 

PROVIDER: S-EPMC10504812 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature