Extrapolating innovations from pediatric clinical trials
While neonates and children have been lumped with pregnant women under
the umbrella of vulnerable populations, numerous advances have led to
success in conducting pediatric clinical trials [46]. Quality of
clinical data in pediatrics has stemmed from the fact that investigators
tend to include multiple drugs in a single protocol, extensive
pharmacokinetic and pharmacodynamic modeling and incorporation of
multiple sites [47]. As for legislative processes, the Best
Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity
Act (PREA) contributed to the development of drug trials in the
pediatric population. The BPCA provided incentive for drug development
and PREA enforces pediatric studies to be conducted of medication that
would help the health of children. Incentives included exclusive
marketing by manufacturers for an additional six month for conducting
pediatric-focused studies, which can translate to up to 500 million
dollars in revenue for each drug [48]. Unfortunately, these do not
yet apply to the pregnant population.
Recent innovations in clinical trial design allowed the development and
use of population-based pharmacokinetic and pharmacodynamic modeling to
better understand the mechanism of drugs within the physiologic milieu
[49, 50]. These advances will likely help optimize selected drug
doses and understand interaction with tissues in an attempt to minimize
unwanted adverse effects to the fetus. These models have been described
by Mendes and Zhang [49, 50]. Population
pharmacokinetics-pharmacodynamics studies have been used in pediatric
clinical trials and have been found to be very helpful as they
incorporate drug properties, physiologic variables, and target tissues
to determine effect [51]. Despite its success in pediatric
populations, its use in the pregnant population seems underutilized.
A multi-disciplinary collaboration is necessary to optimally design and
conduct clinical drug trials in pregnant women. For example, if a
rheumatologist wishes to conduct a trial on effective treatment of
rheumatoid arthritis flare and include pregnant women, a collaboration
with maternal-fetal medicine and neonatology specialists should be
considered to optimize outcome of the study and avoid adverse effect of
treatment or disease on the fetus.