Evaluating biomarkers for prognostic enrichment of clinical trials

Kathleen F. Kerr, Jeremy Roth, Kehao Zhu, Heather Thiessen-Philbrook, Allison Meisner, Francis Perry Wilson, Steven Coca, Chirag R. Parikh

Research output: Contribution to journalArticlepeer-review


Background/Aims: A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. Methods: We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)–(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. Results: We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. Conclusion: In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

Original languageEnglish (US)
Pages (from-to)629-638
Number of pages10
JournalClinical Trials
Issue number6
StatePublished - Dec 1 2017
Externally publishedYes


  • Biomarker
  • clinical trial
  • prognostic enrichment
  • risk prediction

ASJC Scopus subject areas

  • Pharmacology


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