Finite sample variance estimation for optimal dynamic treatment regimes of survival outcomes.

Deriving valid confidence intervals for complex estimators is a challenging task in practice. Estimators of dynamic weighted survival modeling (DWSurv), a method to estimate an optimal dynamic treatment regime of censored outcomes, are asymptotically normal and consistent for their target parameters when at least a subset of the nuisance models is correctly specified. However, their behavior in finite samples and the impact of model misspecification on inferences remain unclear. In addition, the estimators' nonregularity may negatively affect the inferences under some specific data generating mechanisms. Our objective was to compare five methods, two asymptotic variance formulas (adjusting or not for the estimation of nuisance parameters) to three bootstrap approaches, to construct confidence intervals for the DWSurv parameters in finite samples. Via simulations, we considered practical scenarios, for example, when some nuisance models are misspecified or when nonregularity is problematic. We also compared the five methods in an application about the treatment of rheumatoid arthritis. We found that the bootstrap approaches performed consistently well at the cost of longer computational times. The asymptotic variance with adjustments generally yielded conservative confidence intervals. The asymptotic variance without adjustments yielded nominal coverages for large sample sizes. We recommend using the asymptotic variance with adjustments in small samples and the bootstrap if computationally feasible. Caution should be taken when nonregularity may be an issue.