Sex, Drugs, and R&D: Missing Innovation from Regulating Female Enrollment in Clinical Trials

By Valerie Michelman & Lucy Msall. Excerpts:

"Abstract

This  paper  considers  the  consequences  of  unequal  representation  in  research.   From 1977-1993,  the Food and Drug Administration (FDA) issued guidance that “women of  child bearing  potential”  should  not  be  included  as  human  subjects  in  early-stage clinical trials.  We study how the pharmaceutical industry’s response to the guidance shaped  the  course  of  innovation  serving  men  and  women.   We  develop  a  model  of drug development which predicts that the guidance leads to less innovation for female-focused drugs.  Compliance with the guidance decreases the informativeness of clinical trials  for  drugs  intended  to  treat  predominantly  female  diseases,  resulting  in  higher expected costs. To bring our theory to the data, we link biomedical patents, commercial data  on  drug  development,  and  FDA  records  of  approved  drugs.   By  exploiting  the contrast between drug and non-drug biomedical patents, we estimate that the guidance resulted in a sex-specific drug innovation gap of 14%.  We test for downstream effects on drug development and approval.  Our results inform current policy tradeoffs about under representation of racial minorities, pregnant people, and older adults in clinical research."

"In this paper, we study a regulation that restricted female enrollment in drug trials.  The policy provides us the opportunity to quantify how under representation inhuman subjects research distorts who benefits from innovation.  From 1977 to 1993,the U.S. Food and Drug Administration (FDA) instructed drug developers that “pre-menopausal female[s] capable of becoming pregnant” should not be included as human subjects in early stage clinical drug trials.  The category of pre-menopausal women includes all women up to approximately the age of 50.  Pharmaceutical firms considered post-menopausal women a poor substitute, as older adults were usually excluded from early trials during the period for cost reasons.  Therefore the effect of this policy was to ensure that nearly all early stage trials were conducted on men (Goldmann, 1993).See Section 2 for details and Section A.1 for additional context.

Our work is motivated by a simple intuition:  when pre-menopausal women are excluded from initial trials,  the trials generate less information about drug quality for women.  To compensate for this decrease in the informativeness, firms must either conduct additional early trials before deciding whether to proceed to late trials,  or risk committing substantial resources to later trials with less certainty about the outcome.As a result, compliance with the guidance raises the costs of developing drugs to treat predominantly female diseases."