Modeling the causal effect of treatment initiation time on survival: application to HIV/TB co-infection

DOI10.1111/BIOM.12780zbMATH Open1414.62447arXiv1904.01932OpenAlexW2757781177WikidataQ47902131 ScholiaQ47902131MaRDI QIDQ3119902FDOQ3119902

Authors: Liangyuan Hu, Joseph W. Hogan, Ann W. Mwangi, Abraham Siika 

Publication date: 13 March 2019

Published in: Biometrics (Search for Journal in Brave)

Abstract: The timing of antiretroviral therapy (ART) initiation for HIV and tuberculosis (TB) co-infected patients needs to be considered carefully. CD4 cell count can be used to guide decision making about when to initiate ART. Evidence from recent randomized trials and observational studies generally supports early initiation but does not provide information about effects of initiation time on a continuous scale. In this paper, we develop and apply a highly flexible structural proportional hazards model for characterizing the effect of treatment initiation time on a survival distribution. The model can be fitted using a weighted partial likelihood score function. Construction of both the score function and the weights must accommodate censoring of the treatment initiation time, the outcome, or both. The methods are applied to data on 4903 individuals with HIV/TB co-infection, derived from electronic health records in a large HIV care program in Kenya. We use a model formulation that flexibly captures the joint effects of ART initiation time and ART duration using natural cubic splines. The model is used to generate survival curves corresponding to specific treatment initiation times; and to identify optimal times for ART initiation for subgroups defined by CD4 count at time of TB diagnosis. Our findings potentially provide "higher resolution" information about the relationship between ART timing and mortality, and about the differential effect of ART timing within CD4 subgroups.

Full work available at URL: https://arxiv.org/abs/1904.01932

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zbMATH Keywords

marginal structural modelinverse weightinginformative censoringelectronic health recordsantiretroviral therapy (ART)time-varying confounders

Mathematics Subject Classification ID

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

Cited In (10)

• Impact of time to start treatment following infection with application to initiating HAART in HIV-positive patients
• Causal comparative effectiveness analysis of dynamic continuous-time treatment initiation rules with sparsely measured outcomes and death
• On estimating optimal regime for treatment initiation time based on restricted mean residual lifetime
• Estimating heterogeneous survival treatment effect in observational data using machine learning
• Estimating the optimal timing of surgery by imputing potential outcomes
• Estimating the optimal timing of surgery from observational data
• Estimating mean potential outcome under adaptive treatment length strategies in continuous time
• Effect of tuberculosis on immune restoration among HIV-infected patients receiving antiretroviral therapy
• Assessing heterogeneity in treatment initiation guidelines in longitudinal randomized controlled trials
• 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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