Marginal structural models for case-cohort study designs to estimate the association of antiretroviral therapy initiation with incident AIDS or death.
To estimate the association of antiretroviral therapy initiation with incident acquired immunodeficiency syndrome (AIDS) or death while accounting for time-varying confounding in a cost-efficient manner, the authors combined a case-cohort study design with inverse probability-weighted estimation of a marginal structural Cox proportional hazards model. A total of 950 adults who were positive for human immunodeficiency virus type 1 were followed in 2 US cohort studies between 1995 and 2007. In the full cohort, 211 AIDS cases or deaths occurred during 4,456 person-years. In an illustrative 20% random subcohort of 190 participants, 41 AIDS cases or deaths occurred during 861 person-years. Accounting for measured confounders and determinants of dropout by inverse probability weighting, the full cohort hazard ratio was 0.41 (95% confidence interval: 0.26, 0.65) and the case-cohort hazard ratio was 0.47 (95% confidence interval: 0.26, 0.83). Standard multivariable-adjusted hazard ratios were closer to the null, regardless of study design. The precision lost with the case-cohort design was modest given the cost savings. Results from Monte Carlo simulations demonstrated that the proposed approach yields approximately unbiased estimates of the hazard ratio with appropriate confidence interval coverage. Marginal structural model analysis of case-cohort study designs provides a cost-efficient design coupled with an accurate analytic method for research settings in which there is time-varying confounding.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 27599-7435, USA. cole@unc.edu
Stephen R
SR
Cole
Michael G
MG
Hudgens
Phyllis C
PC
Tien
Kathryn
K
Anastos
Lawrence
L
Kingsley
Joan S
JS
Chmiel
Lisa P
LP
Jacobson
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D003362:Cost-Benefit Analysis; D003627:Data Interpretation, Statistical; D015340:Epidemiologic Research Design; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality; D015497:HIV-1; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D015983:Selection Bias; D014481:United States / Q000453:epidemiology
D019380:Anti-HIV Agents