2017 ACC/AAP/AHA Health Policy Statement on Opportunities and Challenges in Pediatric Drug Development: Learning From Sildenafil

T he STARTS-1 and -2 trials (Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension) and subsequent 2012 US Food and Drug Administration (FDA) product labeling for sildenafil use in pediatric patients with pulmonary hypertension highlight many of the challenges to the development and approval of medications for children. This experience served as the impetus for direct collaboration between FDA representatives and the Joint Council on Congenital Heart Disease (JCCHD) (representing the pediatric cardiology leadership of the American College of Cardiology, the American Heart Association, and the American Academy of Pediatrics) to improve communication and realign missions with regard to pediatric drug trials. These discussions led to the joint FDA/JCCHD development of this statement, which describes the current environment and identifies possible future directions for reducing barriers to pediatric drug trials. There are many challenges to the development and approval of medications for children. The STARTS-1 and -2 trials, which are described briefly in the next section, highlight many of the challenges in pediatric trial design and approval of medications for children, especially those with rare diseases. Through a series of conversations between the FDA and JCCHD that had their origin around review of the effect of the STARTS-1 and -2 trials and subsequent regulatory response on clinical practice, it became clear that better communication and alignment of goals surrounding pediatric drug trials were needed. This paper serves as unique opportunity to bring leaders of the pediatric cardiology community and FDA together as 1 voice. Fewer than 50% of drugs approved for use in the United States have sufficient data to support labeling for dosing, safety, and efficacy in children.1,2 Several studies estimate at least 40% and up to 100% of hospitalized children are prescribed at least 1 medication that is used “off-label.”3 …