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research article

Translating questions to estimands in randomized clinical trials with intercurrent events

Stensrud, Mats Julius  
•
Dukes, Oliver
May 16, 2022
Statistics In Medicine

Intercurrent (post-treatment) events occur frequently in randomized trials, and investigators often express interest in treatment effects that suitably take account of these events. Contrasts that naively condition on intercurrent events do not have a straight-forward causal interpretation, and the practical relevance of other commonly used approaches is debated. In this work, we discuss how to formulate and choose an estimand, beyond the marginal intention-to-treat effect, from the point of view of a decision maker and drug developer. In particular, we argue that careful articulation of a practically useful research question should either reflect decision making at this point in time or future drug development. Indeed, a substantially interesting estimand is simply a formalization of the (plain English) description of a research question. A common feature of estimands that are practically useful is that they correspond to possibly hypothetical but well-defined interventions in identifiable (sub)populations. To illustrate our points, we consider five examples that were recently used to motivate consideration of principal stratum estimands in clinical trials. In all of these examples, we propose alternative causal estimands, such as conditional effects, sequential regime effects, and separable effects, that correspond to explicit research questions of substantial interest.

  • Details
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Type
research article
DOI
10.1002/sim.9398
Web of Science ID

WOS:000796383100001

Author(s)
Stensrud, Mats Julius  
•
Dukes, Oliver
Date Issued

2022-05-16

Published in
Statistics In Medicine
Subjects

Mathematical & Computational Biology

•

Public, Environmental & Occupational Health

•

Medical Informatics

•

Medicine, Research & Experimental

•

Statistics & Probability

•

Mathematical & Computational Biology

•

Public, Environmental & Occupational Health

•

Medical Informatics

•

Research & Experimental Medicine

•

Mathematics

•

causal inference

•

estimands

•

identification

•

intercurrent events

•

principal stratification

•

principal stratification

•

exposure-response

•

causal inference

•

identifiability

•

trastuzumab

•

mediation

•

designs

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
BIOSTAT  
Available on Infoscience
June 6, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/188324
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