Defining Efficacy Estimands in Clinical Trials: Examples Illustrating ICH E9(R1) Guidelines.

Published online

Journal Article

This paper provides examples of defining estimands in real-world scenarios following ICH E9(R1) guidelines. Detailed discussions on choosing the estimands and estimators can be found in our companion papers. Three scenarios of increasing complexity are illustrated. The first example is a proof-of-concept trial in major depressive disorder where the estimand is chosen to support the sponsor decision on whether to continue development. The second and third examples are confirmatory trials in severe asthma and rheumatoid arthritis respectively. We discuss the intercurrent events expected during each trial and how they can be handled so as to be consistent with the study objectives. The estimands discussed in these examples are not the only acceptable choices for their respective scenarios. The intent is to illustrate the key concepts rather than focus on specific choices. Emphasis is placed on following a study development process where estimands link the study objectives with data collection and analysis in a coherent manner, thereby avoiding disconnect between objectives, estimands, and analyses.

Full Text

Duke Authors

Cited Authors

  • Ratitch, B; Goel, N; Mallinckrodt, C; Bell, J; Bartlett, JW; Molenberghs, G; Singh, P; Lipkovich, I; O'Kelly, M

Published Date

  • April 9, 2019

Published In

Start / End Page

  • 2168479019841316 -

PubMed ID

  • 30966778

Pubmed Central ID

  • 30966778

Electronic International Standard Serial Number (EISSN)

  • 2168-4804

Digital Object Identifier (DOI)

  • 10.1177/2168479019841316

Language

  • eng

Conference Location

  • United States