The Ethical Dilemma across history
Prioritizing protection of the fetus was an important factor that
prevented pregnant women to participate in clinical drug trials. Several
federal regulations now request clarification on inclusion criteria by
defining whether the fetus or the pregnant woman are being targeted, and
whether the study aims to highlight therapeutic or non-therapeutic
outcomes [8]. In 1974, after the devastating thalidomide disaster,
congress asked the newly established National Commission for the
Protection of Human Subjects of Biomedical and Behavioral Research to
make recommendations for the conduct of research involving pregnant
women and fetuses (Federal regulations at subpart B of 45 CFR 46)
[9]. Dr. Kelsey, who was the primary reviewer of the thalidomide
application assigned by the FDA, delayed the approval of thalidomide
over concerns of adverse effects and the drug was never approved in the
United States [10]. The aim of the recommendations thus was to
protect the fetus from unnecessary harm. More than twenty years later
and after much deliberation, the wording was changed in 2001 to include
a more proscriptive approach; stating that pregnant women or fetuses may
be involved in research if all of 10 conditions are met (Table
1) . In 2002, a registry for reporting adverse effects was established.
In 2004, the FDA developed the guidance on pharmacokinetic (PK) studies
in pregnancy, and, in 2005, guidance was provided on clinical lactation
studies and pregnancy [11]. In 2009, the Second Wave Initiative was
launched aiming to systematically address the knowledge gap on treatment
of pregnant women in a collaborative manner [12]. The FDA has also
addressed drug labeling to include risk summary and clinical
consideration in an effort to improve patient care decision and
counseling under the Pregnancy and Lactation Labeling Rule (PLLR)
[7]. This was first proposed in 2008 with the revised version put in
action in 2014. While much has been done to support the moral imperative
of including pregnant women, much more needs to be done to ensure that
we provide pregnant women with beneficence, autonomy, and justice.