Biomarkers Consortium - Workshop: Defining an Evidentiary Criteria Framework for Surrogate Endpoint Qualification

The Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium, in partnership with the Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research, hosted a public meeting entitled Framework for Defining Evidentiary Criteria: Surrogate Endpoint Qualification Workshop on July 30th and 31st, 2018.

This workshop aimed to create alignment among scientific stakeholders including FDA, NIH, the biopharmaceutical industry, academic researchers and patient groups regarding a proposed framework for determining the levels of evidence required to qualify biomarkers for use in drug development, with an emphasis on surrogate endpoints. A primary aim of the meeting was to elaborate the general framework for biomarker qualification along with specific application to different contexts of use (COUs), including assessment of several representative case studies involving surrogate endpoint markers of specific clinical outcome measures.

Surrogate Endpoint Core Program Committee:

Stacey Adam - Director Cancer, FNIH

Ken Anderson -Program Director, Dana–Farber Cancer Institute

Steve Broadbent – Chief Operating Officer, Critical Path Institute

Martha Brumfield - President & CEO, Critical Path Institute

Sara Eggers - Office of Strategic Programs, FDA/CDER

Steve Hoffmann - Director Inflammation and Immunity, FNIH

Laura Jaeger - Scientific Policy Advisor, FDA/CDER

Reza Kazemi-Tabriz – Operations Research Analyst, FDA/CDER

Gary Kelloff - Special Advisor and Biomarkers Consortium Cancer Steering Committee Co-Chair, NCI/NIH

Leila Lackey - Operations Research Analyst, FDA/CDER

Chris Leptak - Director Biomarker Qualification Program and Biomarkers Consortium Executive Committee Member, FDA

Lisa McShane – Sr. Statistician, NIH/NCI

Joseph Menetski - Associate VP Research Partnerships, FNIH

Theresa Mullin - Associate Director for Strategic Initiatives, FDA/CDER

Elizabeth Ottinger - Senior Project Manager, NIH/NCATS

James Revkin – Senior Director, Pfizer

John-Michael Sauer - Executive Director, Predictive Safety Testing Consortium, Critical Path Institute

Myrlene Staten – Program Director and Biomarkers Consortium Metabolic Disorders Steering Committee Co-Chair NIH/NIDDK

Adeline Vanderver - Program Director of the Leukodystrophy CoE, Children’s Hospital of Philadelphia

John Wagner - Senior VP and Biomarkers Consortium Executive Committee Member, Takeda

Steve Williams - Chief Medical Officer, SomaLogic Inc

Robert Wolk – Director, Pfizer

Presentations from the Workshop:

Surrogate Endpoint Qualification Workshop Introduction
Joseph Menetski, Ph.D.
Associate Vice President of Research Partnerships
Foundation for the National Institutes of Health

Brief Overview of Biomarkers: Value, Limitations, and the
Biomarker Qualification Program

Peter Stein, M.D.
Deputy Director
Office New Drugs, CDER
U.S. Food & Drug Administration

21st Century Cures Biomarker Qualification :Updates, Deliverables, and Progress Towards Defined Evidence
Christopher Leptak, M.D., Ph.D.
Director of the Biomarker Qualification Program
Office New Drugs, CDER
U.S. Food & Drug Administration

A Framework for Defining Evidentiary Criteria for Biomarker Qualification
John Wagner, M.D., Ph.D.
Senior Vice President and Head
Clinical and Translational Sciences
Takeda Pharmaceutical International

Thoughts on Evidentiary Criteria for Biomarker Qualification:
A “Decision Science” Perspective

Reza Kazemi-Tabriz, Ph.D.
Performance Analysis and Data Services Staff Director
U.S. Food & Drug Administration

Concepts and Case Study Template for Surrogate Endpoints Workshop
Lisa M. McShane, Ph.D.
Acting Associate Director, Division of Cancer Treatment and Diagnosis
National Cancer Institute
National Institutes of Health

LDL-C and HDL-C as Surrogate Endpoints
James Revkin, M.D.
Senior Director, Global Clinical Lead

Minimal Residual Disease (MRD) in Multiple Myeloma (MM)
Ken Anderson, M.D.
Chief, Division of Hematologic Neoplasia
Director of the Jerome Lipper Multiple Myeloma Center and
Vice Chair of the Joint Program in Transfusion Medicine, Dana-Farber Cancer Institute

Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease
Arlene Chapman, M.D.
Professor of Medicine, Chief, Section of Nephrology, Department of Medicine
University of Chicago

Alexander Disease
Adeline Vanderver, M.D., Amy Waldman, M.D., MSCE
Leukodystrophy Center of Excellence, Children's Hospital of Philadelphia
Albee Messing, VMD, Ph.D.
Waisman Center, University of Wisconsin - Madison

Case Study Framework Summaries


  • Improve the quality and standardization of submissions to the FDA
  • Better characterize and define surrogate endpoints for drug development through example case studies
  • Support FDA in the development of Guidance(s) for the level of evidentiary criteria sufficient for surrogate endpoint qualification

Results & Accomplishments

Guidance Documents

FDA Facts: Biomarkers and Surrogate Endpoints

Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics, May 2017

Surrogate Endpoint Resources for Drug and Biologic Development

Table of Surrogate Endpoints That Were the Basis of Drug Approval or Licensure

Considerations for Discussion of a New Surrogate Endpoint(s) at a Type C PDUFA Meeting Request (PDF-111KB)

BEST Resource Taxonomy

Scientific Publications

What evidence do we need for biomarker qualification? Leptak G, Menetski JP, Wagner JA, Aubrecht J, Brady L, Brumfield M, Chin WW, Hoffmann S, Kelloff G, Lavezzari G, Ranganathan R, Sauer J-M, Sistare FD, Zabka T, Wholley D. Sci Transl Med. 2017 Nov 22;9(417).

Evidentiary Criteria Framework Final Version

Workshop Agenda


FNIH Web Announcement (Dec. 7, 2017): Science Translational Medicine Publishes Article on Evidence Needed for Biomarker Qualification


Children's Hospital of Philadelphia

Critical Path Institute

Dana-Farber Cancer Institute

Food and Drug Administration 

National Cancer Institute (NCI)

National Center for Advancing Translational Sciences (NCATS)

Pfizer Inc

University of Chicago


Joseph Menetski, Associate Vice President, Research Partnerships,