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

Bohdana Ratitch, Niti Goel, Craig Mallinckrodt, James Bell, Jonathan W Bartlett, Geert Molenberghs, Pritibha Singh, Ilya Lipkovich, Michael O'Kelly

Research output: Contribution to journalArticle

113 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalTherapeutic Innovation & Regulatory Science
Early online date9 Apr 2019
DOIs
Publication statusE-pub ahead of print - 9 Apr 2019

Cite this

Defining Efficacy Estimands in Clinical Trials: Examples Illustrating ICH E9(R1) Guidelines. / Ratitch, Bohdana; Goel, Niti; Mallinckrodt, Craig; Bell, James; Bartlett, Jonathan W; Molenberghs, Geert; Singh, Pritibha; Lipkovich, Ilya; O'Kelly, Michael.

In: Therapeutic Innovation & Regulatory Science, 09.04.2019, p. 1-15.

Research output: Contribution to journalArticle

Ratitch, Bohdana ; Goel, Niti ; Mallinckrodt, Craig ; Bell, James ; Bartlett, Jonathan W ; Molenberghs, Geert ; Singh, Pritibha ; Lipkovich, Ilya ; O'Kelly, Michael. / Defining Efficacy Estimands in Clinical Trials: Examples Illustrating ICH E9(R1) Guidelines. In: Therapeutic Innovation & Regulatory Science. 2019 ; pp. 1-15.
@article{ed3816b2a9a442ee9f025eb776d8a537,
title = "Defining Efficacy Estimands in Clinical Trials: Examples Illustrating ICH E9(R1) Guidelines",
abstract = "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.",
author = "Bohdana Ratitch and Niti Goel and Craig Mallinckrodt and James Bell and Bartlett, {Jonathan W} and Geert Molenberghs and Pritibha Singh and Ilya Lipkovich and Michael O'Kelly",
year = "2019",
month = "4",
day = "9",
doi = "10.1177/2168479019841316",
language = "English",
pages = "1--15",
journal = "Therapeutic Innovation & Regulatory Science",
issn = "2168-4790",
publisher = "Sage Publications",

}

TY - JOUR

T1 - Defining Efficacy Estimands in Clinical Trials: Examples Illustrating ICH E9(R1) Guidelines

AU - Ratitch, Bohdana

AU - Goel, Niti

AU - Mallinckrodt, Craig

AU - Bell, James

AU - Bartlett, Jonathan W

AU - Molenberghs, Geert

AU - Singh, Pritibha

AU - Lipkovich, Ilya

AU - O'Kelly, Michael

PY - 2019/4/9

Y1 - 2019/4/9

N2 - 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.

AB - 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.

U2 - 10.1177/2168479019841316

DO - 10.1177/2168479019841316

M3 - Article

SP - 1

EP - 15

JO - Therapeutic Innovation & Regulatory Science

JF - Therapeutic Innovation & Regulatory Science

SN - 2168-4790

ER -