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research article

Estimation of separable direct and indirect effects in continuous time

Martinussen, Torben
•
Stensrud, Mats Julius  
September 27, 2021
Biometrics

Many research questions involve time-to-event outcomes that can be prevented from occurring due to competing events. In these settings, we must be careful about the causal interpretation of classical statistical estimands. In particular, estimands on the hazard scale, such as ratios of cause-specific or subdistribution hazards, are fundamentally hard to interpret causally. Estimands on the risk scale, such as contrasts of cumulative incidence functions, do have a clear causal interpretation, but they only capture the total effect of the treatment on the event of interest; that is, effects both through and outside of the competing event. To disentangle causal treatment effects on the event of interest and competing events, the separable direct and indirect effects were recently introduced. Here we provide new results on the estimation of direct and indirect separable effects in continuous time. In particular, we derive the nonparametric influence function in continuous time and use it to construct an estimator that has certain robustness properties. We also propose a simple estimator based on semiparametric models for the two cause-specific hazard functions. We describe the asymptotic properties of these estimators and present results from simulation studies, suggesting that the estimators behave satisfactorily in finite samples. Finally, we reanalyze the prostate cancer trial from Stensrud et al. (2020).

  • Details
  • Metrics
Type
research article
DOI
10.1111/biom.13559
Web of Science ID

WOS:000700218800001

Author(s)
Martinussen, Torben
Stensrud, Mats Julius  
Date Issued

2021-09-27

Published in
Biometrics
Volume

79

Issue

1

Start page

127

End page

139

Subjects

Biology

•

Mathematical & Computational Biology

•

Statistics & Probability

•

Life Sciences & Biomedicine - Other Topics

•

Mathematics

•

competing events

•

hazard functions

•

influence function

•

separable effects

•

survival analysis

•

causal inference

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
BIOSTAT  
Available on Infoscience
October 9, 2021
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/181942
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