Download A US Perspective - Global Forum on Bioethics in Research

Research With Pregnant Women
Permissible Regulations, Cautious Practice:
A US Perspective
Anna C. Mastroianni, JD, MPH
Professor of Law, University of Washington School of Law
Associate Director, Institute for Public Health Genetics
Seattle, USA
Leslie Meltzer Henry, JD, PhD
Professor of Law, University of Maryland Carey School of Law
Core Faculty, Johns Hopkins Berman Institute of Bioethics
Baltimore, USA
Orientation
• United States permits pregnant women’s participation in research
under conditions specified in regulations and official guidances
• Facilitated through local IRB review with national oversight
• “Subpart B” [Additional Protections for Pregnant Women, Human
Fetuses and Neonates Involved in Research] regulations set up ethical
framework, with extensive reach and international influence
• Permissibility stymied by regulatory and other legal obstacles
www.pregnancyethics.org
The Reach of Subpart B
NIH-Funded Research
Research Funded by U.S. Agency
that Follows Subpart B
Conducted Inside or Outside of the
United States
Conducted Inside or Outside of the
United States
SUBPART B APPLIES
Any Funder
Any Funder
Research Conducted at an FWA
Institution Inside or Outside of
the United States
Research Team Member Affiliated
with FWA Institution Inside or
Outside of the United States
www.pregnancyethics.org
US Regulatory Approach to Common Ethical Issues
Presumption
of Inclusion
“Pregnant women or fetuses may be involved in research if all
of the following conditions are met…” (2001)
Contrast ICH “ In general, pregnant women should be excluded
…where drug not intended for use in pregnancy”
Population
Classified as
Vulnerable
“IRB…should be particularly cognizant of the special problems of
research involving vulnerable populations, such as…pregnant
women…..”
Contrast ICH: “special population” with “unique risk/benefit
considerations “ or “modification of use of the dose or schedule
of a drug “ and “attention… to informed consent.”
www.pregnancyethics.org
US Regulatory Approach to Common Ethical Issues
Benefit-Risk
Prospect of
direct
benefit to
woman or
fetus
“risk to the fetus is caused solely by
interventions or procedures that hold out the
prospect of direct benefit for the woman or
the fetus”
No
prospect of
direct
benefit to
woman or
fetus
Where “no such prospect of benefit, the risk
to the fetus is not greater than minimal” and
research purpose is “development of
important biomedical knowledge which
cannot be obtained by any other means”
www.pregnancyethics.org
Additional Mechanism for Approving Research
with Pregnant Women
• Standard: “reasonable opportunity to further the
understanding, prevention, or alleviation of a serious problem
affecting the health or welfare of pregnant women [or] fetuses
…”
• Process: Decision by Secretary of Health and Human Services,
after consultation with expert panel, public comment, and
public meeting
www.pregnancyethics.org
US Regulatory Approach to Common Ethical
Issues: Paternal Consent
• Inform of “reasonably foreseeable impact of the research on the
fetus”
• Additional consent of father required if research holds out
prospect of direct benefit solely to the fetus
• Exceptions: unavailability, incompetence, temporary incapacity,
pregnancy resulted from rape or incest.
www.pregnancyethics.org
Default Approach 
De Facto Exclusion of Pregnant Women
Many researchers and institutional review boards (IRBs) continue to regard
pregnancy as a near-automatic cause for exclusion, regardless of the costs of
exclusion or the magnitude or likelihood of the risks of participation.
A. Lyerly, M. Little & R. Faden. The second wave: toward responsible inclusion of pregnant women in research.
Real-Life Implications
• Fewer than 20 FDA-approved drugs are approved for use during
pregnancy
• Mean time for determining risk of medication in pregnancy: 27 years postdrug approval
www.pregnancyethics.org
Legal Obstacles
Lawyers are active and influential participants in
decisionmaking throughout the research process
• Regulatory Ambiguity and Inconsistency
• Legal Risk Management
• Litigation Climate and “Long Tail” Liability Concerns
• Insurance Availability
• Compensation Availability
• Venue-Specific Laws
• International Complexity
• Fetal Protection Laws
www.pregnancyethics.org
Acknowledgments
www.pregnancyethics.org