FDA Redefines Expectations for Clinical Trials in Children and Pregnant Women 
​​[Posted on: Thursday, April 12, 2018]

Two new FDA guidance documents discuss the practical and regulatory aspects of testing new products in children and pregnant women confirming the well-established industry practices for these populations. Both documents emphasize the need to test new drugs in children and pregnant women only when absolutely necessary and to use alternate data sources to reduce clinical testing in these populations. Pregnant women are generally not included in most clinical trials due to concerns for the health of the fetus. Hence nonclinical data is extrapolated to project response in pregnant women. However, pregnant women are almost as likely to need treatments as any other population but both the patients and the prescribers are reluctant to use a given new treatment owing to the lack of the appropriate clinical data. On the other hand, it is required by law to test new drugs and biologics in children. Under the Pediatric Drug Equity Act (PREA) of 2003, drugs must be tested in pediatric and adult populations unless it is well established that the target disease does not occur in children. That said, most drugs are first tested in adults and many a times approved based on data from adults, with pediatric studies conducted later in the development program leading to delays in FDA approval of pediatric use. For pregnant women, FDA sets 10 conditions that must be met to test new drugs. There must be data from non-clinical and non-pregnant women indication any potential risks before testing in pregnant women. The projected risk to fetus, based on non-clinical data, must be minimal and justification for generating clinical data in fetus be established. Risk to the fetus must be minimized. Proper informed consent from the pregnant woman, and in some cases, from the father of the fetus, must be obtained disclosing the foreseeable risks. And the research team must have no role in determining timing, methods or procedures for termination of pregnancy, if needed, or the viability of the neonate. As a general rule, FDA wants the sponsors of clinical trials to only do trials in pregnant women when the risk is minimal based on other data, and there is a reasonably high likelihood of benefit to the participant. FDA is fine with moving the clinical trials in pregnant women to post-market phase of the drug. None of this should come as a surprise to experienced drug developers as this is an established practice already. Children are involved in about 20% of all clinical trials and most clinical trials in pediatric populations are conducted for pediatric indications where the disease either does not occur in adults or is less prevalent. Before conducting a pediatric study, FDA expects sponsors to first justify the dose, biological effect, safety and potential efficacy based on existing knowledge which includes evidence generated in adult with the same disease or condition, where possible, nonclinical data, data about related compounds, disease pathophysiology, as well as consideration of the developmental physiology of the relevant pediatric populations. Safety can be extrapolated from adult populations in most cases, and efficacy can be predicted using simulations and computational modeling. The guidance goes on to describe the various aspects of pediatric clinical trial development which are standard across the industry such as feasibility, risk assessment, formulation changes, pathphysiological considerations between pediatric and adult populations, population segmentation by age and physiology, and other factors. In general, both the guidance documents reconfirm common sense and, by most accounts, currently well established industry practices for clinical trials in pediatric patients and pregnant women. There are no surprises here.