Impact of copula directional specification on multi-trial evaluation of surrogate end points

Lindsay A. Renfro, Hongwei Shang, Daniel J. Sargent

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Evaluation of surrogate end points using patient-level data from multiple trials is the gold standard, where multi-trial copula models are used to quantify both patient-level and trial-level surrogacy. While limited consideration has been given in the literature to copula choice (e.g., Clayton), no prior consideration has been given to direction of implementation (via survival vs. distribution functions). We demonstrate that even with the "correct" copula family, directional misspecification leads to biased estimates of patient-level and trial-level surrogacy. We illustrate with a simulation study and a reanalysis of disease-free survival as a surrogate for overall survival in early stage colon cancer.

Original languageEnglish (US)
Pages (from-to)857-877
Number of pages21
JournalJournal of Biopharmaceutical Statistics
Volume25
Issue number4
DOIs
StatePublished - Jul 4 2015

Keywords

  • Clinical trials
  • Copula
  • Meta-analysis
  • Surrogate end points
  • Survival copula

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Statistics and Probability

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