Causal comparative effectiveness analysis of dynamic continuous-time treatment initiation rules with sparsely measured outcomes and death

DOI10.1111/BIOM.13018MaRDI QIDQ5214532zbMATH OpenOpenAlexWikidataFDO

Authors Liangyuan Hu, Joseph W. Hogan

Publication date 7 February 2020

Published in Biometrics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1904.01668

zbMATH Keywords

marginal structural modelmultiple imputationinverse weightingelectronic health recordshuman immunodeficiency virus/acquired immunodeficiency syndrome

Mathematics Subject Classification ID

Reliability and life testing (62N05) Applications of statistics to biology and medical sciences; meta analysis (62P10)

Abstract: Evidence supporting the current World Health Organization recommendations of early antiretroviral therapy (ART) initiation for adolescents is inconclusive. We leverage a large observational data and compare, in terms of mortality and CD4 cell count, the dynamic treatment initiation rules for HIV-infected adolescents. Our approaches extend the marginal structural model for estimating outcome distributions under dynamic treatment regimes (DTR), developed in Robins et al. (2008), to allow the causal comparisons of both specific regimes and regimes along a continuum. Furthermore, we propose strategies to address three challenges posed by the complex data set: continuous-time measurement of the treatment initiation process; sparse measurement of longitudinal outcomes of interest, leading to incomplete data; and censoring due to dropout and death. We derive a weighting strategy for continuous time treatment initiation; use imputation to deal with missingness caused by sparse measurements and dropout; and define a composite outcome that incorporates both death and CD4 count as a basis for comparing treatment regimes. Our analysis suggests that immediate ART initiation leads to lower mortality and higher median values of the composite outcome, relative to other initiation rules.

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(9)

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• Estimating the optimal timing of surgery by imputing potential outcomes
• Assessing heterogeneity in treatment initiation guidelines in longitudinal randomized controlled trials
• Estimation of the marginal effect of antidepressants on body mass index under confounding and endogenous covariate-driven monitoring times
• A flexible sensitivity analysis approach for unmeasured confounding with multiple treatments and a binary outcome with application to SEER-medicare lung cancer data

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