Post-Approval Pediatric Use of Drugs Granted Waivers from Pediatric Testing.
Half of the drugs granted pediatric testing waivers are used in children, suggesting a need for post-approval studies to ensure safety.
Where it sits
this study against the rest of the leuprorelin corpusSummary and findings
The study evaluated the pediatric use of drugs granted waivers from pediatric testing using a commercial claims database. Among 291 drugs with waivers, 147 showed pediatric use within three years of approval. Median pediatric users per month was 0.47, with some drugs having substantial off-label use.
Abstract
The Pediatric Research Equity Act mandates new drugs be tested in children before Food and Drug Administration (FDA) approval, though roughly one-fifth of these drugs are granted complete waivers from pediatric testing. With the high prevalence of these waivers, US children may be at risk of being treated by drugs without pediatric testing (and therefore with unclear risk-benefit profiles). We evaluated how often drugs granted pediatric testing waivers are prescribed in US children using a large commercial claims database. Using public FDA data, we identified drugs granted pediatric testing waivers from 2007 to 2022 that did not report pediatric testing prior to FDA approval. We used the Merative MarketScan Commercial Database to determine monthly pediatric users for the first 36 months after approval. We defined "pediatric users" as the number of unique pediatric patients with ≥1 dispensing in a month. Among 291 drugs granted waivers from pediatric testing, 147 (51%) had observable pediatric use in the first 3 years following approval. Median summed users was 17 (interquartile range [IQR], 3-102), with median 0.47 users/month (IQR, 0.08-2.83). Among the top 20 most-used drugs, pediatric users ranged from 508 (valsartan/hydrochlorothiazide) to 22,111 (conjugated estrogen cream) (median 1,050.5; IQR, 709.5-1,690.8), with a median of 29.2 users/month (IQR, 19.7-47.0). Among drugs granted waivers from pediatric trials, half have observable off-label use in children in the 3 years after FDA approval. Routine clinical use evidence from these prescriptions could be collected to inform drug labeling updates, and some drugs have sufficient use to make post-approval pediatric studies feasible.
Background
The study addresses the concern that drugs granted waivers from pediatric testing may still be used in children, potentially exposing them to untested treatments. The Pediatric Research Equity Act requires pediatric testing for new drugs, but waivers are sometimes granted, leaving a gap in safety and efficacy data for pediatric populations. Understanding the extent of off-label pediatric use is crucial for assessing the need for post-approval studies.
Methods
The study used a large commercial claims database to evaluate the pediatric use of drugs granted waivers from pediatric testing. Drugs were identified using public FDA data from 2007 to 2022. Pediatric users were defined as unique patients with at least one dispensing in a month, tracked for the first 36 months post-approval. The primary outcome was the number of pediatric users per drug.
Results
Among 291 drugs with waivers, 147 (51%) had observable pediatric use within three years post-approval. The median number of summed pediatric users was 17, with an interquartile range of 3 to 102. The median number of users per month was 0.47, with an IQR of 0.08 to 2.83. For the top 20 most-used drugs, pediatric users ranged from 508 to 22,111, with a median of 1,050.5 users.
Interpretation
The findings suggest that a significant proportion of drugs granted pediatric testing waivers are used off-label in children. While the median use is low, some drugs have substantial pediatric use, indicating a potential need for post-approval studies to ensure safety and efficacy. The study highlights the importance of monitoring off-label use to inform potential updates to drug labeling.
Key findings
- 291 drugs granted waivers from pediatric testing.
- 147 drugs (51%) had observable pediatric use in the first 3 years.
- Median summed users was 17 (IQR, 3-102).
- Median 0.47 users/month (IQR, 0.08-2.83).
- Pediatric users for top 20 drugs ranged from 508 to 22,111.
Limitations
- Observational study design.
- Reliance on claims data.
- Potential underreporting of pediatric use.
- No causal inference possible.