02: Analysis of Analytic Treatment Interruption Trials with Misclassified Interval-Censored

Music City Center 

Analytical treatment interruption (ATI) trials involve interruption of antiretroviral therapy (ART) in order to evaluate the efficacy of novel treatments for HIV. In these trials, the primary outcome of interest is often the time to viral rebound: the time from ART interruption until the participant's viral load crosses a predetermined threshold. Due to the discrete nature of clinical visit schedules, this time to viral rebound is interval-censored, though many ATI studies implicitly right-impute the failure time. Furthermore, measurement error and the non-monotonicity of the HIV viral load trajectory may lead the first threshold-crossing event to be missed entirely by the intermittent viral load measurements. We conduct a simulation study to evaluate the performance of the Cox proportional hazards model and log-rank test on misclassified interval-censored data, both with and without right imputation of the rebound time. We also investigate how aspects of the ATI trial design may mediate the impact of these data characteristics on the Cox model and log-rank test performance. Finally, we make recommendations based on our results for best practices for ATI trials.

HIV/AIDS

clinical trials

interval censoring

misclassification

Cox proportional hazards model

log-rank test 

Biometrics Section