Survival Analysis of Drug Combinations Using a Hazards Model with Time-Dependent Covariates

Abstract

Hazard functions in cancer chemotherapeutic situations may not be proportional, so a nonproportional hazard model has been developed. The dose-response surface is explored by regression analysis of experimental data, and after the estimation of the underlying hazard function the quality of the fit of the model is assessed. Further, treatment levels may be optimized, and estimated survival distributions can be plotted for any treatment combination. In an example of two-drug treatment of murine L1210 leukemia, statistically significant nonproportionality is determined. Analysis permits extraction of potentially important information on drug interrelationships, which has been previously unavailable.

Direct search methods in the optimisation of cancer chemotherapy regimens

“…This possibility may be investigated by performing two or more searches with differently located starting complexes. However, the problem may be unimportant in the present context, for adequately characterised biological response surfaces have so far all shown single optima (Carter et al, 1977(Carter et al, , 1982(Carter et al, , 1985Gennings et al, 1988;Solana et al, 1986;Stablein et al, 1980;Staniswalis & McCrady, 1988;Wampler et al, 1978;Wilson et al, 1986).…”

Everolimus With Very Low-Exposure Cyclosporine A in De Novo Kidney Transplantation: A Multicenter, Randomized, Controlled Trial

“…To estimate the effect of the concentration of the drugs on the risk of BPAR, a survival analysis of EVL and CsA blood levels combinations using a Hazard model with time-dependent covariates was performed (9).…”

Comparing proportional hazards and accelerated failure time models for survival analysis

“…Estimation of the parameters will require the maximization of the partial likelihood function [22] giving the following estimates and standard errors: In this example, the additional exibility for the hazard function indicates that there is a signiÿcant treatment di erence. However, this e ect disappears when the survival time of the patients increases, reaching slightly better results for long-term survivors by using the combined treatment [16].…”