Estimands for overall survival in clinical trials with treatment switching in oncology.
ITT
cross-over
estimand
overall survival
treatment switching
Journal
Pharmaceutical statistics
ISSN: 1539-1612
Titre abrégé: Pharm Stat
Pays: England
ID NLM: 101201192
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
28
04
2021
received:
21
05
2020
accepted:
10
07
2021
pubmed:
5
10
2021
medline:
27
1
2022
entrez:
4
10
2021
Statut:
ppublish
Résumé
An addendum of the ICH E9 guideline on Statistical Principles for Clinical Trials was released in November 2019 introducing the estimand framework. This new framework aims to align trial objectives and statistical analyses by requiring a precise definition of the inferential quantity of interest, that is, the estimand. This definition explicitly accounts for intercurrent events, such as switching to new anticancer therapies for the analysis of overall survival (OS), the gold standard in oncology. Traditionally, OS in confirmatory studies is analyzed using the intention-to-treat (ITT) approach comparing treatment groups as they were initially randomized regardless of whether treatment switching occurred and regardless of any subsequent therapy (treatment-policy strategy). Regulatory authorities and other stakeholders often consider ITT results as most relevant. However, the respective estimand only yields a clinically meaningful comparison of two treatment arms if subsequent therapies are already approved and reflect clinical practice. We illustrate different scenarios where subsequent therapies are not yet approved drugs and thus do not reflect clinical practice. In such situations the hypothetical strategy could be more meaningful from patient's and prescriber's perspective. The cross-industry Oncology Estimand Working Group (www.oncoestimand.org) was initiated to foster a common understanding and consistent implementation of the estimand framework in oncology clinical trials. This paper summarizes the group's recommendations for appropriate estimands in the presence of treatment switching, one of the key intercurrent events in oncology clinical trials. We also discuss how different choices of estimands may impact study design, data collection, trial conduct, analysis, and interpretation.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
150-162Informations de copyright
© 2021 John Wiley & Sons Ltd.
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