S15: Inclusion of Pediatric Participants in Clinical Trials: Which Regulatory Process is Better, BPCA or NDA?
University of Southern California United States
To determine whether clinical trials (CTs) are inclusive of the pediatric population through a comparison of CT data for drugs approved under the Best Pharmaceuticals for Children Act (BPCA) versus drugs approved via New Drug Approvals (NDA).
CTs for drugs receiving marketing exclusivity from 2016-2018 under the BPCA were compiled using Clinicaltrials.gov. For comparison purposes, information from FDA.gov about CTs for drugs approved via a NDA pathway from 2016-2018 were compiled from the approval drug labels and Drug Trials Snapshot.
Between 2016 and 2018, the U.S. Food and Drug Administration (FDA) approved 127 New Drug Applications (NDA). Of these NDAs, 31 drugs were approved for use by the pediatric population. Of these 31 drugs, 25 drugs (80.6%) included information on pediatric participants in their clinical trials and their approved drug labels. Most of these clinical studies tested the intervention in both adult and pediatric populations. For the rest of the drugs, two drugs (0.06%) demonstrated their efficacy and safety for pediatric use through extrapolation of studies with adult clinical trial participants, three drugs (0.10%) mentioned that additional safety studies involving pediatric population were conducted but did not refer to the number of pediatric participants in their approved drug labels, and one drug (0.03%) utilized animal studies to prove safety and efficacy for pediatric use. In the same time period (2016 to 2018), 22 drugs received marketing exclusivity under the BPCA, and of these drugs, 18 drugs (82%) resulted in a pediatric indication as result of additional pediatric clinical studies. For all 22 drugs, a total of 196 CTs were found within clinicaltrials.gov. Of these studies, 135 studies were open to both adult and pediatric populations, ten were available to the entire pediatric population, and 51 were available to specific pediatric sub-populations. Due to exclusion criteria, only 118 of the CTs, where both pediatric and adult populations were eligible, were assessed and 65 of these had less than 1% pediatric representation.
From CT data for drugs approved under the BPCA versus NDA pathways, the majority of studies included both adults and pediatrics to demonstrate safety and efficacy of the therapeutic intervention in the pediatric population. For the BPCA, there is an increasing trend of CTs, where adults and pediatrics are eligible, compared to pediatric or pediatric subpopulations. In 2016, pediatric subpopulation CTs were the majority of studies conducted, but none for 2017, and only 7 of 86 CTs in 2018. This indicates a reliance on CTs where both adults and pediatrics are eligible to fulfill FDA requests for pediatric CTs. In fact, 65% of drugs that have pediatric indications had more studies conducted involving adults and pediatrics than pediatric or pediatric sub-populations. Whereas for the NDA pathway, more drugs are being approved for pediatric indications (n= 6 in 2016, n=8 in 2017, and n=17 in 2018). This does not necessarily indicate an increased pediatric participation in clinical trials for these medications because in both 2016 and 2017, the safety and efficacy of one drug for pediatric use was supported by data extrapolation of clinical studies open only to adults. For NDAs approved in 2018 with pediatric indications, the approved drug labels of three drugs indicate additional safety data was collected from pediatric participants but do not contain the sample size or demographic data and one NDA used data from animal studies to prove safety and efficacy for pediatric use. This comparison of CT information for drugs used by the pediatric population approved through BPCA and NDA pathways shows an increasing numbers of drugs are being approved for use by the pediatric population, that clinical studies conducted to prove the pediatric indication tend to incorporate subjects from both adult and pediatric populations, and that pediatric indications do not always necessarily correlate to pediatric-specific dosage and administration instructions.