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Semiparametric regression analysis of clustered survival data with semi-competing risks

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  • Peng, Mengjiao
  • Xiang, Liming
  • Wang, Shanshan

Abstract

Analysis of semi-competing risks data is becoming increasingly important in medical research in which a subject may experience both nonterminal and terminal events, and the time to the intermediate nonterminal event (e.g. onset of a disease) is subject to dependent censoring by the terminal event (e.g. death) but not vice versa. Typically, both two types of events are dependent. In many applications, subjects may also be nested within clusters, such as patients in a multi-center study, leading to possible association among event times due to unobserved shared factors across subjects. To incorporate dependency within clusters and association between two types of event times, we propose a new flexible semiparametric modeling framework where a copula model is employed for the joint distribution of the nonterminal and terminal events, and their marginal distributions are modeled by Cox proportional hazards models with random effects. A nonparametric maximum likelihood estimation procedure is developed and implemented through a Monte Carlo EM algorithm. The proposed estimator is also shown to enjoy desirable asymptotic properties. Results from extensive simulation studies indicate that the proposed method performs very well in finite samples and is especially robust against misspecification of the random effects distribution. We further illustrate the practical utility of the method by analyzing data from a multi-institutional study of breast cancer.

Suggested Citation

  • Peng, Mengjiao & Xiang, Liming & Wang, Shanshan, 2018. "Semiparametric regression analysis of clustered survival data with semi-competing risks," Computational Statistics & Data Analysis, Elsevier, vol. 124(C), pages 53-70.
    • Handle: RePEc:eee:csdana:v:124:y:2018:i:c:p:53-70
    DOI: 10.1016/j.csda.2018.02.003
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    References listed on IDEAS

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    Cited by:

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    2. Murray, James & Philipson, Pete, 2022. "A fast approximate EM algorithm for joint models of survival and multivariate longitudinal data," Computational Statistics & Data Analysis, Elsevier, vol. 170(C).
    3. Annalisa Orenti & Patrizia Boracchi & Giuseppe Marano & Elia Biganzoli & Federico Ambrogi, 2022. "A pseudo-values regression model for non-fatal event free survival in the presence of semi-competing risks," Statistical Methods & Applications, Springer;Società Italiana di Statistica, vol. 31(3), pages 709-727, September.
    4. Xifen Huang & Jinfeng Xu & Hao Guo & Jianhua Shi & Wenjie Zhao, 2022. "An MM Algorithm for the Frailty-Based Illness Death Model with Semi-Competing Risks Data," Mathematics, MDPI, vol. 10(19), pages 1-13, October.
    5. Bo-Hong Wu & Hirofumi Michimae & Takeshi Emura, 2020. "Meta-analysis of individual patient data with semi-competing risks under the Weibull joint frailty–copula model," Computational Statistics, Springer, vol. 35(4), pages 1525-1552, December.
    6. Philipson, Pete & Hickey, Graeme L. & Crowther, Michael J. & Kolamunnage-Dona, Ruwanthi, 2020. "Faster Monte Carlo estimation of joint models for time-to-event and multivariate longitudinal data," Computational Statistics & Data Analysis, Elsevier, vol. 151(C).
    7. Murray, James & Philipson, Pete, 2023. "Fast estimation for generalised multivariate joint models using an approximate EM algorithm," Computational Statistics & Data Analysis, Elsevier, vol. 187(C).
    8. Zhang, Cuihong & Ning, Jing & Cai, Jianwen & Squires, James E. & Belle, Steven H. & Li, Ruosha, 2024. "Dynamic risk score modeling for multiple longitudinal risk factors and survival," Computational Statistics & Data Analysis, Elsevier, vol. 189(C).
    9. Luiza S. C. Piancastelli & Wagner Barreto-Souza & Vinícius D. Mayrink, 2021. "Generalized inverse-Gaussian frailty models with application to TARGET neuroblastoma data," Annals of the Institute of Statistical Mathematics, Springer;The Institute of Statistical Mathematics, vol. 73(5), pages 979-1010, October.

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