The value of surrogate endpoints for predicting real-world survival across five cancer types

Jason Shafrin, Ron Brookmeyer, Desi Peneva, Jinhee Park, Jie Zhang, Robert A. Figlin, Darius N. Lakdawalla

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints - progression-free survival (PFS) and time to progression (TTP) - to predict real-world OS across five cancers.Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan-Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991-2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R2 from linear regressions.Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P = 0.026). Among all real-world patients using sample treatments (N = 309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P = 0.194). Results were qualitatively similar using median absolute prediction error and R2 metrics.Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone.

Original languageEnglish (US)
Pages (from-to)731-739
Number of pages9
JournalCurrent Medical Research and Opinion
Issue number4
StatePublished - Apr 2 2016


  • Comparative effectiveness research
  • neoplasms
  • observational study
  • progression-free survival
  • surrogate endpoints
  • survival

ASJC Scopus subject areas

  • Medicine(all)


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