SP02-32: Examination of FDA Pediatric Regulations: Inclusion of Pediatric Participants in Clinical Trials
University of Southern California United States
Assess the impact of the Best Pharmaceuticals for Children Act (BCPA).
Drugs approved by the FDA from 2016 to 2018 following adoption of the BPCA were assessed. Clinical studies data available in Clinicaltrials.gov were categorized as including both pediatric and adult populations, only a pediatric population, and pediatric sub-populations.
Between 2016 and 2018, following passage of the BCPA, 26 drugs were approved by the FDA. In 2016, 2 drugs were approved, and 27 clinical trials were conducted. Of these clinical trials, 10 studies were open to both adults and pediatrics, but 2 studies were excluded due to ambiguous data presentation and lack of pediatric data, leaving 8 available for assessment. Examples of ambiguous data presentation include not providing separate pediatric statistics, grouping pediatric and adult populations together (i.e. ages 15 to 64 years), and solely presenting reduced data such as means and standard deviations. This made it difficult to determine which data represented the pediatric population. Of the 10 studies, 2 had less than 1% pediatric representation. In 2017, 11 drugs were approved, and 69 clinical trials were conducted. Of these clinical trials, 41 studies were open to both adults and pediatrics, but 3 studies were excluded, leaving 38 for assessment. Of the 38 studies, 25 had less than 1% pediatric representation. In 2018, 13 drugs were approved, and 124 clinical trials were conducted. Of the 124 clinical trials, 101 studies were open to both adults and pediatrics, but 12 studies were excluded, leaving 89 studies for assessment. Of the 89 studies, 54 had less than 1% pediatric representation. From an assessment of 135 clinical trials, where both pediatric and adult populations were eligible, there is a clear lack of standardization in terms of which ages constitute a particular pediatric sub-population even though guidelines for these sub-populations exist under the BCPA. Because of lacking standardization of ages and presentation of data, the data could not be examined on an equivalent basis. Instead, the information for each drug was examined separately for pediatric inclusion. Of all 26 drugs, 23 had at least 1 study with less than 1% of pediatrics representation in studies open to both groups. This is alarming as these drugs are currently used by pediatrics.
From 2016 to 2018, 154 studies, where both pediatric and adult populations were eligible, were conducted for 26 drugs approved under the BPCA. A significant number, 19 studies (12.3%), were excluded due to ambiguous data presentation. An examination of the remaining 135 studies (87.7%) revealed:
• There is a lack of standardization of which ages constitute a pediatric sub-population even though guidelines for these sub-populations exist from the Center for Drug Evaluation and Research (CDER).
• There is a lack of pediatric representation in clinical trials involving both adults and pediatrics.
• There is a lack of adequate presentation of data and inclusion of all pediatric sub-populations.
There is a need for incentives and revised legislation requiring harmonized presentation of pediatric data in clinical trials, because drugs approved post-BPCA are utilized by pediatrics. Crucial information, such as dosage, will be revealed from this harmonization, leading to more accurate and informative pediatric drug labels. Safe labeling of medication for pediatrics remains a serious public health challenge. In 2014, Children’s Hospital Los Angeles reported 15,145 in-patient visits and estimated 26,503 out-patient visits who could have benefited from access to clinical trials. Additionally, the Centers for Disease Control and Prevention (CDC) reports more than 60,000 U.S. children visit emergency rooms annually due to adverse drug effects. Moreover, the findings of this study demonstrate that a lack of pediatric information can affect therapeutic areas associated with pediatrics. This is consistent with the Report to Congress regarding Pediatric Labeling of Orphan Drugs in 2019 which found 127 out of 221 indications pertaining to pediatrics lacked pediatric information or missing information for particular sub-populations. Ultimately, a more informative pediatric drug label informs prescribers and the caretakers of children.