Semiparametric regression analysis for time-to-event marked endpoints in cancer studies

Chen Hu, Alex Tsodikov

Research output: Contribution to journalArticle

Abstract

In cancer studies the disease natural history process is often observed only at a fixed, random point of diagnosis (a survival time), leading to a current status observation (Sun (2006). The statistical analysis of interval-censored failure time data. Berlin: Springer.) representing a surrogate (a mark) (Jacobsen (2006). Point process theory and applications: marked point and piecewise deterministic processes. Basel: Birkhauser.) attached to the observed survival time. Examples include time to recurrence and stage (local vs. metastatic). We study a simple model that provides insights into the relationship between the observed marked endpoint and the latent disease natural history leading to it. A semiparametric regression model is developed to assess the covariate effects on the observed marked endpoint explained by a latent disease process. The proposed semiparametric regression model can be represented as a transformation model in terms of mark-specific hazards, induced by a process-based mixed effect. Large-sample properties of the proposed estimators are established. The methodology is illustrated by Monte Carlo simulation studies, and an application to a randomized clinical trial of adjuvant therapy for breast cancer.

Original languageEnglish (US)
Pages (from-to)513-525
Number of pages13
JournalBiostatistics
Volume15
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Keywords

  • Disease natural history
  • Marked endpoints
  • Semiparametric regression

ASJC Scopus subject areas

  • Medicine(all)
  • Statistics and Probability
  • Statistics, Probability and Uncertainty

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