Sep 21, 2019 Volume 394 Number 10203 p979-1112
Prescribing off-label drugs for children: when will it change?
A study in Pediatrics, published on Sept 16, paints a familiar picture. Using data from the US National Ambulatory Medical Care Surveys 2006–15, Divya Hoon and colleagues show that in 44·5% of visits to office-based physicians who prescribed systemic drugs to children, these drugs were prescribed off label. Off-label prescription can be outside the approved age, weight, dose, formulation, route of administration, or indication. In this study, 74·6% of all off-label prescriptions were for an unapproved disorder for the specific drug and 17·6% were off-label by age. Over the study period, there was a rise in off-label orders by indication and the reasons varied by age group. There were more off-label prescriptions for gastrointestinal disorders in the youngest age groups and for psychiatric disorders in the older age groups. Studies of inpatient care have shown even higher percentages, especially for off-label drug use in the neonatal and paediatric intensive-care setting.
Progress to address this issue has been slow. The first paediatric drug development incentive legislation was introduced as part of the US Food and Drug Administration (FDA) Modernization Act more than 20 years ago. This law was followed by the Best Pharmaceutical for Children Act in 2002 and the Pediatric Research Equity Act (PREA) in 2003. Under PREA, the FDA is allowed to require paediatric studies of any drug likely to be used in a substantial number of children or when there are no good alternatives for children. Yet a study published last year showed that at the time of approval only 18 of 114 new drugs or new indications for drugs that would fall under the PREA requirement had any information on efficacy, safety, or dosing in children. Furthermore, after a median follow-up of 6·8 years, only 47 of 114 had any paediatric information.
Children are not small adults and evidence-based treatment is arguably even more important in children. Both the potential of adverse events with lifelong consequences and the danger of ineffective drugs with poor outcomes have far-reaching consequences. The current efforts are woefully inadequate.