A computationally simple bivariate survival estimator for efficacy and safety

Denise Scholtens, Rebecca Betensky

Research output: Contribution to journalArticle

Abstract

Both treatment efficacy and safety are typically the primary endpoints in Phase II, and even in some Phase III, clinical trials. Efficacy is frequently measured by time to response, death, or some other milestone event and thus is a continuous, possibly censored, outcome. Safety, however, is frequently measured on a discrete scale; in Eastern Cooperative Oncology Group clinical trial E2290, it was measured as the number of weekly rounds of chemotherapy that were tolerable to colorectal cancer patients. For the joint analysis of efficacy and safety, we propose a non-parametric, computationally simple estimator for the bivariate survival function when one time-to-event is continuous, one is discrete, and both are subject to right-censoring. The bivariate censoring times may depend on each other, but they are assumed to be independent of both event times. We derive a closed-form covariance estimator for the survivor function which allows for inference to be based on any of several possible statistics of interest. In addition, we derive its covariance with respect to calendar time of analysis, allowing for its use in sequential studies.

Original languageEnglish (US)
Pages (from-to)365-387
Number of pages23
JournalLifetime Data Analysis
Volume12
Issue number3
DOIs
StatePublished - Sep 1 2006

Fingerprint

Efficacy
Safety
Estimator
Survival
Oncology
Chemotherapy
Clinical Trials
Colorectal Cancer
Right Censoring
Phase III Clinical Trials
Calendar
Statistics
Survival Function
Censoring
Survivors
Colorectal Neoplasms
Closed-form
Drug Therapy

Keywords

  • Bivariate survival
  • Efficacy and safety
  • Group sequential analysis

ASJC Scopus subject areas

  • Medicine(all)
  • Applied Mathematics

Cite this

A computationally simple bivariate survival estimator for efficacy and safety. / Scholtens, Denise; Betensky, Rebecca.

In: Lifetime Data Analysis, Vol. 12, No. 3, 01.09.2006, p. 365-387.

Research output: Contribution to journalArticle

Scholtens, Denise ; Betensky, Rebecca. / A computationally simple bivariate survival estimator for efficacy and safety. In: Lifetime Data Analysis. 2006 ; Vol. 12, No. 3. pp. 365-387.
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