Flexible modeling of the hazard rate and treatment effects in long-term survival studies.
The effects of predictors on time to failure may be difficult to assess in cancer studies with longer follow-up, as the commonly used assumption of proportionality of hazards holding over an extended period is often questionable. Motivated by a long-term prostate cancer clinical trial, we contrast and compare four powerful methods for estimation of the hazard rate. These four methods allow for varying degrees of smoothness as well as covariates with effects that vary over time. We pay particular attention to an extended multiresolution hazard estimator, which is a flexible, semi-parametric, Bayesian method for joint estimation of predictor effects and the hazard rate. We compare the results of the extended multiresolution hazard model to three other commonly used, comparable models: Aalen's additive model, Kooperberg's hazard regression model, and an extended Cox model. Through simulations and the analysis of a large-scale randomized prostate cancer clinical trial, we use the different methods to examine patterns of biochemical failure and to estimate the time-varying effects of androgen deprivation therapy treatment and other covariates.
1 Department of Applied Mathematics, University of Colorado, CO, USA.
Yolanda
Y
Hagar
2 Department of Public Health Sciences, University of Chicago, IL, USA.
James J
JJ
Dignam
1 Department of Applied Mathematics, University of Colorado, CO, USA.
Vanja
V
Dukic
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
D000726:Androgen Antagonists
Biochemical failure; hazard rate; multiresolution hazard; non-proportional hazards; prostate cancer; survival analysis