Pediatric drug information available at the time of new drug approvals: A cross-sectional analysis.

PURPOSE: Greater than 50% of drugs lack pediatric labeling information, resulting in widespread "off-label" use in children. To increase pediatric prescribing information, the Pediatric Research Equity Act (PREA) was passed in 2003, requiring new drug applications to include pediatric assessments. We evaluated the study of new drugs in children since PREA was implemented. METHODS: We performed a cross-sectional analysis of new drug applications submitted to the FDA from December 2003 to July 2012, using publicly available documents at Drugs@FDA. We calculated the proportion of new drugs that included a pediatric assessment at the time of approval and at a final review performed in July 2016. RESULTS: We identified 92 new drugs requiring pediatric assessments. Only 20 (21.7%) had been fully studied in children at the time of approval, while 9 (9.8%) had been partially assessed, and 63 (68.5%) did not have pediatric data. Among drugs approved without pediatric assessments, 4.2% met FDA deferral deadlines and 34.9% eventually submitted pediatric data. At the time of our final review, allowing for a mean of 8.6 years since drug approval, 57.6% of new drugs had not been fully assessed in children. The mean time between approval in adults and availability of pediatric data for drugs approved without pediatric assessments was 6.5 years. CONCLUSIONS: These results represent a comprehensive evaluation of the study of new drugs in children and demonstrate that many drugs continue to be approved without pediatric data. Our findings serve to inform approaches to strengthen adherence to PREA requirements.

Evaluation of FDA Labeling Changes Related to PREA Safety-Waivers.

PURPOSE: The Pediatric Research Equity Act (PREA) gives the US Food and Drug Administration (FDA) authority to require pediatric studies for drug and biologics products under certain circumstances and to waive this requirement in some, or all, pediatric ages. When studies are waived for safety, PREA stipulates the safety issue must be described in labeling. This study assessed the rate of including waiver-related safety information in labeling. METHODS: FDA databases were reviewed to determine the number of safety-related pediatric study waivers and issued from December 2003 through August 2020, and corresponding labeling to establish when relevant safety information was included. Descriptive comparisons were conducted across Cohort 1: December 2003-2007, Cohort 2: 2008-2011, Cohort 3: 2012-2015, and Cohort 4: 2016-August 2020. RESULTS: One hundred sixteen safety waivers were issued [Cohort 1 (n = 1); Cohort 2 (n = 38), Cohort 3 (n = 37), and Cohort 4 (n = 40)] for 84 unique drugs or biologics. Most (106 of 116; 91%) waiver-related safety issues were described in labeling [Cohort 1 (1 of 1), Cohort 2 (33 of 38), Cohort 3 (33 of 37), and Cohort 4 (39 of 40)]. Safety waivers were most common in patients ≤ 17 years (n = 40) and least common in patients ≤ 6 months (n = 15). Products for infections (n = 32) were the most common group receiving safety waivers; 17 for non-antiviral anti-infective products including treatments for dermatologic infestations/infections, and 15 for antiviral products. CONCLUSION: The data confirm that FDA consistently describes waiver-related safety information in drug/biologic product labeling since the inception of PREA in December of 2003.