Biological Variability to Drug Response: Sex Difference in Clinical Trials


FDA Convening

Biological Variability to Drug Response: Sex Difference in Clinical Trials

May 16, 2016 — 12:00AM–{12}:{00}{AM}


Gregory Daniel, PhD, MPH
Ruthanna Davi, PhD
Garret FitzGerald, MD
David J. Greenblatt, MD
Mark McClellan, MD, PhD
Virginia M. Miller, MBA, PhD
Rita F. Redberg, MD, MSc
Rick Sax, MD
Jerald S. Schindler, DrPH
Robert Temple, MD
John J. Whyte, MD, MPH
Janet Woodcock, MD


We know there is biologic variability to drug response. What we don’t know is what those major causes of variability are. The U.S. Food and Drug Administration (FDA) is being asked to ensure pivotal trials are adequately powered to detect demographic differences of sex, race, age, and ethnicity on drug safety and efficacy. Yet the hypothesis-driven, population-mean-based results of randomized clinical trials (RCTs) are not designed to yield definitive insights into the differential responses of subgroups, or for that matter, any individual.

Given that a randomized clinical trial cannot test every subgroup, how do we determine which subgroups actually matter? If we believe there is a biologic plausibility that a certain subgroup will respond differently to the same drug, how do we design a trial to capture that difference? How much confidence do we have in that finding? How much uncertainty are we comfortable with? How can we as a scientific community, improve the nature of the “learn-confirm” clinical trial process to better understand variability in drug response? And are there viable alternatives to RCTs that may be more useful in identifying meaningful differences in drug response?

Acknowledging that the randomized control trial is not the only solution, and may not even be the best approach, the FDA called a meeting to discuss best practices to understanding variability to drug response. Duke-Margolis hosted s hosting this day-long meeting in collaboration with experts from government, academia, industry, and patient advocacy groups to discuss biologic variability in regard to FDA CDER-approved drugs and biologics.

Funding for this conference was made possible in part by a cooperative agreement from the Food and Drug Administration. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services nor does mention of trade names, commercial practices, or organizations imply endorsements by the U.S. Government.