Causal Multistate Models to Evaluate Treatment Delay

Statistics in Medicine, vol. 44, pp. e70061

Abstract

Multistate models allow for the study of scenarios where individuals experience different events over time. While effective for descriptive and predictive purposes, multistate models are not typically used for causal inference. We propose an estimator that combines a multistate model with g-computation to estimate the causal effect of treatment delay strategies. In particular, we estimate the impact of strategies such as awaiting natural recovery for 3 months, on the marginal probability of recovery. We use an illness-death model, where illness and death represent, respectively, treatment and recovery. We formulate the causal assumptions needed for identification and the modeling assumptions needed to estimate the quantities of interest. In a simulation study, we present scenarios where the proposed method can make more efficient use of data compared to an alternative approach using cloning-censoring-reweighting. We then showcase the proposed methodology on real data by estimating the effect of treatment delay on a cohort of 1896 couples with unexplained subfertility who seek intrauterine insemination.

Authors 4

1. Ilaria Prosepe corresponding Aachen Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center

   Affiliation as printed

   Department of Biomedical Data Sciences Leiden University Medical Center Leiden the Netherlands

2. Saskia le Cessie Aachen Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center

   Affiliation as printed

   Department of Biomedical Data Sciences Leiden University Medical Center Leiden the Netherlands

   Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands

3. Hein Putter Aachen Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center

   Affiliation as printed

   Department of Biomedical Data Sciences Leiden University Medical Center Leiden the Netherlands

4. Nan van Geloven Aachen Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

   Leiden University Medical Center

   Affiliation as printed

   Department of Biomedical Data Sciences Leiden University Medical Center Leiden the Netherlands