With advances in biomedical research, biomarkers are becoming increasingly important prognostic factors for predicting overall survival, while the measurement of biomarkers is often censored due to instruments' lower limits of detection. This leads to two types of censoring: random censoring in overall survival outcomes and fixed censoring in biomarker covariates, posing new challenges in statistical modeling and inference. Existing methods for analyzing such data focus primarily on linear regression ignoring censored responses or semiparametric accelerated failure time models with covariates under detection limits (DL). In this paper, we propose a quantile regression for survival data with covariates subject to DL. Comparing to existing methods, the proposed approach provides a more versatile tool for modeling the distribution of survival outcomes by allowing covariate effects to vary across conditional quantiles of the survival time and requiring no parametric distribution assumptions for outcome data. To estimate the quantile process of regression coefficients, we develop a novel multiple imputation approach based on another quantile regression for covariates under DL, avoiding stringent parametric restrictions on censored covariates as often assumed in the literature. Under regularity conditions, we show that the estimation procedure yields uniformly consistent and asymptotically normal estimators. Simulation results demonstrate the satisfactory finite‐sample performance of the method. We also apply our method to the motivating data from a study of genetic and inflammatory markers of Sepsis.
Popular parametric and semiparametric hazards regression models for clustered survival data are inappropriate and inadequate when the unknown effects of different covariates and clustering are complex. This calls for a flexible modeling framework to yield efficient survival prediction. Moreover, for some survival studies involving time to occurrence of some asymptomatic events, survival times are typically interval censored between consecutive clinical inspections. In this article, we propose a robust semiparametric model for clustered interval‐censored survival data under a paradigm of Bayesian ensemble learning, called soft Bayesian additive regression trees or SBART (Linero and Yang, 2018), which combines multiple sparse (soft) decision trees to attain excellent predictive accuracy. We develop a novel semiparametric hazards regression model by modeling the hazard function as a product of a parametric baseline hazard function and a nonparametric component that uses SBART to incorporate clustering, unknown functional forms of the main effects, and interaction effects of various covariates. In addition to being applicable for left‐censored, right‐censored, and interval‐censored survival data, our methodology is implemented using a data augmentation scheme which allows for existing Bayesian backfitting algorithms to be used. We illustrate the practical implementation and advantages of our method via simulation studies and an analysis of a prostate cancer surgery study where dependence on the experience and skill level of the physicians leads to clustering of survival times. We conclude by discussing our method's applicability in studies involving high‐dimensional data with complex underlying associations.
more » « less- NSF-PAR ID:
- 10397102
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Biometrics
- Volume:
- 78
- Issue:
- 3
- ISSN:
- 0006-341X
- Format(s):
- Medium: X Size: p. 880-893
- Size(s):
- ["p. 880-893"]
- Sponsoring Org:
- National Science Foundation
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Failure time data subject to various types of censoring commonly arise in epidemiological and biomedical studies. Motivated by an AIDS clinical trial, we consider regression analysis of failure time data that include exact and left‐, interval‐, and/or right‐censored observations, which are often referred to as partly interval‐censored failure time data. We study the effects of potentially time‐dependent covariates on partly interval‐censored failure time via a class of semiparametric transformation models that includes the widely used proportional hazards model and the proportional odds model as special cases. We propose an EM algorithm for the nonparametric maximum likelihood estimation and show that it unifies some existing approaches developed for traditional right‐censored data or purely interval‐censored data. In particular, the proposed method reduces to the partial likelihood approach in the case of right‐censored data under the proportional hazards model. We establish that the resulting estimator is consistent and asymptotically normal. In addition, we investigate the proposed method via simulation studies and apply it to the motivating AIDS clinical trial.
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