Post-Approval Pediatric Use of Drugs Granted Waivers from Pediatric Testing

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.