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Clin Trials. 2017 Dec;14(6):629-638. doi: 10.1177/1740774517723588. Epub 2017 Aug 10.

Evaluating biomarkers for prognostic enrichment of clinical trials.

Author information

1
1 Department of Biostatistics, University of Washington, Seattle, WA, USA.
2
2 Program of Applied Translational Research, Yale University School of Medicine and VA Medical Center, New Haven, CT, USA.
3
3 Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
4 Section of Nephrology, Yale University School of Medicine, New Haven, CT, USA.

Abstract

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.

KEYWORDS:

Biomarker; clinical trial; prognostic enrichment; risk prediction

PMID:
28795578
PMCID:
PMC5714681
DOI:
10.1177/1740774517723588
[Indexed for MEDLINE]
Free PMC Article

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