Skip to main content
Journal cover image

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

Publication ,  Journal Article
Ratitch, B; Bell, J; Mallinckrodt, C; Bartlett, JW; Goel, N; Molenberghs, G; O'Kelly, M; Singh, P; Lipkovich, I
Published in: Ther Innov Regul Sci
March 2020

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Ther Innov Regul Sci

DOI

EISSN

2168-4804

Publication Date

March 2020

Volume

54

Issue

2

Start / End Page

324 / 341

Location

Switzerland

Related Subject Headings

  • Statistics & Probability
  • Research Design
  • Quality of Life
  • Models, Statistical
  • Data Interpretation, Statistical
  • 4905 Statistics
  • 3214 Pharmacology and pharmaceutical sciences
  • 1117 Public Health and Health Services
  • 0104 Statistics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ratitch, B., Bell, J., Mallinckrodt, C., Bartlett, J. W., Goel, N., Molenberghs, G., … Lipkovich, I. (2020). Choosing Estimands in Clinical Trials: Putting the ICH E9(R1) Into Practice. Ther Innov Regul Sci, 54(2), 324–341. https://doi.org/10.1007/s43441-019-00061-x
Ratitch, Bohdana, James Bell, Craig Mallinckrodt, Jonathan W. Bartlett, Niti Goel, Geert Molenberghs, Michael O’Kelly, Pritibha Singh, and Ilya Lipkovich. “Choosing Estimands in Clinical Trials: Putting the ICH E9(R1) Into Practice.Ther Innov Regul Sci 54, no. 2 (March 2020): 324–41. https://doi.org/10.1007/s43441-019-00061-x.
Ratitch B, Bell J, Mallinckrodt C, Bartlett JW, Goel N, Molenberghs G, et al. Choosing Estimands in Clinical Trials: Putting the ICH E9(R1) Into Practice. Ther Innov Regul Sci. 2020 Mar;54(2):324–41.
Ratitch, Bohdana, et al. “Choosing Estimands in Clinical Trials: Putting the ICH E9(R1) Into Practice.Ther Innov Regul Sci, vol. 54, no. 2, Mar. 2020, pp. 324–41. Pubmed, doi:10.1007/s43441-019-00061-x.
Ratitch B, Bell J, Mallinckrodt C, Bartlett JW, Goel N, Molenberghs G, O’Kelly M, Singh P, Lipkovich I. Choosing Estimands in Clinical Trials: Putting the ICH E9(R1) Into Practice. Ther Innov Regul Sci. 2020 Mar;54(2):324–341.
Journal cover image

Published In

Ther Innov Regul Sci

DOI

EISSN

2168-4804

Publication Date

March 2020

Volume

54

Issue

2

Start / End Page

324 / 341

Location

Switzerland

Related Subject Headings

  • Statistics & Probability
  • Research Design
  • Quality of Life
  • Models, Statistical
  • Data Interpretation, Statistical
  • 4905 Statistics
  • 3214 Pharmacology and pharmaceutical sciences
  • 1117 Public Health and Health Services
  • 0104 Statistics