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  • Article
    A Proportional Hazards Mixture Cure Model for Subgroup Analysis: Inferential Method and an Application to Colon Cancer Data
    (MDPI, 2025) Liu, Kai; Balakrishnan, Narayanaswamy; Peng, Yingwei
    When determining subgroups with heterogeneous treatment effects in cancer clinical trials, the threshold of a variable that defines subgroups is often pre-determined by physicians based on their experience, and the optimality of the threshold is not well studied, particularly when the mixture cure rate model is considered. We propose a mixture cure model that allows optimal subgroups to be estimated for both the time to event for uncured subjects and the cure status. We develop a smoothed maximum likelihood method for the estimation of model parameters. An extensive simulation study shows that the proposed smoothed maximum likelihood method provides accurate estimates. Finally, the proposed mixture cure model is applied to a colon cancer study to evaluate the potential differences in the treatment effect of levamisole plus fluorouracil therapy versus levamisole alone therapy between younger and older patients. The model suggests that the difference in the treatment effect on the time to cancer recurrence for uncured patients is significant between patients younger than 67 and patients older than 67, and the younger patient group benefits more from the combined therapy than the older patient group.
  • Article
    Afthd: Bayesian Accelerated Failure Time Model for High-Dimensional Time-To Data
    (Springernature, 2025) Kumari, Pragya; Bhattacharjee, Atanu; Vishwakarma, Gajendra K.; Tank, Fatih
    Analyzing high-dimensional (HD) data with time-to-event outcomes poses a formidable challenge. The accelerated failure time (AFT) model, an alternative to the Cox proportional hazard model in survival analysis, lacks sufficient R packages for HD time-to-event data under the Bayesian paradigm. To address this gap, we develop the R package afthd. This tool facilitates advanced AFT modeling, offering Bayesian analysis for univariate and multivariable scenarios. This work includes diagnostic plots and an open-source R code for working with HD data, extending the conventional AFT model to the Bayesian framework of log-normal, Weibull, and log-logistic AFT models. The methodology is rigorously validated through simulation techniques, yielding consistent results across parametric AFT models. The application part is also performed on two different real HD liver cancer datasets, which reveals the proposed method's significance by obtaining inferences for survival estimates for the disease. Our developed package afthd is competent in working with HD time-to-event data using the conventional AFT model along with the Bayesian paradigm. Other aspects, like missing values in covariates within HD data and competing risk analysis, are also covered in this article.