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Use of Time-Dependent Propensity Scores to Adjust Hazard Ratio Estimates in Cohort Studies with Differential Depletion of Susceptibles

    Basic Details

    Estimating hazard ratios (HR) presents challenges for time-to-event analyses of cohorts with differential depletion of susceptibles. When the treatment effect is not null, cohorts that were balanced at baseline tend to become unbalanced on baseline characteristics over time as 'susceptible' individuals drop out of the population at risk differentially across treatment groups due to having outcome events. Here, we present results from a series of simulations to help analysts gain insight on these issues. We propose a novel approach that uses time-dependent PSs to consistently estimate conditional HRs, regardless of whether susceptibles have been depleted differentially. Simulations show that adjustment for time-dependent PSs can adjust for covariate imbalances over time that are caused by depletion of susceptibles. Updating the PS is unnecessary when outcome incidence is so low that depletion of susceptibles is negligible. But if incidence is high, and covariates and treatment affect risk, then covariate imbalances arise as susceptibles are depleted, and PS-based methods can consistently estimate the conditional HR only if the PS is periodically updated.


    Richard Wyss, Joshua Gagne, Yueqin Zhao, Esther Zhou, Jacqueline Major, Shirley Wang, Rishi Desai, Jessica Franklin, Sebastian Schneeweiss, Sengwee Toh, Margaret Johnson, Bruce Fireman

    Corresponding Author

    Richard Wyss, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.