Abstract
OBJECTIVE: To compare restricted mean survival time- (RMST-) based methods with traditional survival methods when multiple covariates are of interest. METHODS: 4405 osteosarcomas were captured from Surveillance, Epidemiology, and End Results Program Database. RMST-based methods included group comparison using Kaplan-Meier (KM) method, pseudovalue (PV) regression, and inverse probability of censoring probability (IPCW) regressions with group-specific and individual weights. Log-rank test, Wilcoxon test, Cox regression, and its extension with time-dependent variables were selected as traditional methods. Proportional hazard (PH) assumption and homogeneity of censoring mechanism assumption were assessed. We estimated hazard ratio (HR) and difference in RMST and explored their relationships. RESULTS: When covariate violated PH assumption, time-varying HR was inconvenient to report as a single value but PH assumption-free RMST allowed to report a single value of difference in RMST. In univariable analyses, using the difference in RMST calculated by KM method as reference, PV regressions (slope = 1.02 and R (2) = 0.98) and IPCW regressions with group-specific weights (slope = 0.98 and R (2) = 0.99) gave more consistent estimation than IPCW with individual weights (slope = 0.31 and R (2) = 0.06), moreover, PV regressions presented more robust statistical power than IPCW regressions with group-specific weights. In multivariable analyses, IPCW regression with group-specific weights was limited when multiple covariates violated homogeneity of censoring mechanism assumption. For covariates met PH assumption, well-fitted logarithmic relationships between HR and difference in RMST estimated by PV regression were observed in both univariable and multivariable analyses (R (2) = 0.97 and R (2) = 0.94, respectively), which supported the robustness of PV regression and possible conversion between the two effect measures. CONCLUSIONS: Difference in RMST is more interpretable than time-varying HR. The performance supports KM method and PV regression to be the preferred ones in RMST-based methods. IPCW regression can be an alternative sensitivity analysis. We encourage adoption of both traditional methods and RMST-based methods to present effects of covariates comprehensively.