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.