Promises, Pitfalls, and Paths Forward for the Pediatric Research Equity Act.

Importance: Since its enactment in 2003, the Pediatric Research Equity Act (PREA) has significantly increased the number of pediatric drug studies performed and expanded pediatric drug labeling. Despite these advancements, many drugs used in children still lack pediatric-specific US Food and Drug Administration (FDA) labeling, even when pediatric studies are required by law. Recent legislative changes strengthened the FDA's enforcement authority over PREA. As these changes are implemented, persistent gaps in pediatric drug development warrant examination. Addressing these gaps may help ensure that children are systematically included in clinical research and that medications used in children are supported by rigorous evidence on safety, dosing, and efficacy. Observations: Legislation to ensure pediatric drug safety and efficacy has a long history, yet pediatric-specific labeling frequently lags behind initial drug approval, with many studies required under PREA remaining incomplete for years after initial FDA approval. Consequently, off-label prescribing can be necessary for pediatric health care, leaving children exposed to medications lacking adequate pediatric evidence. Barriers to the timely completion of clinical trials are often attributed to challenges inherent to smaller, disease-specific pediatric populations; however, the FDA's limited enforcement authority and insufficient resources to address delayed pediatric trial completion play an underappreciated role. In addition, limited ability to track required studies and insufficient public transparency undermine the regulatory goals intended to protect children. With new legislative authority strengthening enforcement of PREA, understanding these barriers is essential to ensure this authority is effectively deployed to improve children's health. Conclusions and Relevance: To ensure children have access to safe, effective, evidence-based medications, effective policy changes are necessary. The FDA should use its new authority to ensure the timely completion of required pediatric studies and enhance public transparency by improving mechanisms to track PREA-mandated research.