Choosing Estimands in Clinical Trials: Putting the ICH E9(R1) Into Practice.

Published online

Journal Article

The National Research Council (NRC) Expert Panel Report on Prevention and Treatment of Missing Data in Clinical Trials highlighted the need for clearly defining objectives and estimands. That report sparked considerable discussion and literature on estimands and how to choose them. Importantly, consideration moved beyond missing data to include all postrandomization events that have implications for estimating quantities of interest (intercurrent events, aka ICEs). The ICH E9(R1) draft addendum builds on that research to outline key principles in choosing estimands for clinical trials, primarily with focus on confirmatory trials. This paper provides additional insights, perspectives, details, and examples to help put ICH E9(R1) into practice. Specific areas of focus include how the perspectives of different stakeholders influence the choice of estimands; the role of randomization and the intention-to-treat principle; defining the causal effects of a clearly defined treatment regimen, along with the implications this has for trial design and the generalizability of conclusions; detailed discussion of strategies for handling ICEs along with their implications and assumptions; estimands for safety objectives, time-to-event endpoints, early-phase and one-arm trials, and quality of life endpoints; and realistic examples of the thought process involved in defining estimands in specific clinical contexts.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • April 4, 2019

Published In

Start / End Page

  • 2168479019838827 -

PubMed ID

  • 30947539

Pubmed Central ID

  • 30947539

Electronic International Standard Serial Number (EISSN)

  • 2168-4804

Digital Object Identifier (DOI)

  • 10.1177/2168479019838827

Language

  • eng

Conference Location

  • United States