Health Policy Statement Tackles Opportunities and Challenges of Pediatric Drug Development

There are many challenges to the development and approval of medications for children. A new health policy statement published in the Journal of the American College of Cardiology on June 29 describes the current environment and identifies possible future directions for reducing barriers to pediatric drug trials.

The writing committee, chaired by Craig A. Sable, MD, FACC, explain that the STARTS-1 and -2 trials (Sildenafil in Treatment-Naïve Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension) raised concerns about sildenafil therapy in children, resulting in labeling from the U.S. Food and Drug Administration (FDA) stating the use of sildenafil was not recommended in pediatric patients with pulmonary hypertension. This experience led to direct collaboration between FDA representatives and the Joint Council on Congenital Heart Disease (JCCHD) – which represents pediatric cardiology leadership of the ACC, the American Heart Association and the American Academy of Pediatrics – to improve communication and realign missions regarding pediatric drug trials.

Some characteristics of the pediatric population pose challenges to the development of pediatric drug trials. Infants and children go through stages of rapid growth and development that can alter the pharmacokinetics and pharmacodynamics of some therapeutics. The long life expectancy of children can make appropriate study endpoints difficult to define. Additionally, the ethics of clinical research in children remain a significant issue. The small population of children affected by cardiovascular disease also makes it difficult to design well-powered randomized clinical trials to test the effectiveness and safety of new therapeutics.

Going forward, the writing committee says that investigators studying therapeutics in children may need to consider alternatives to the classic randomized, controlled trial design, such as adaptive trial designs. Novel techniques, such as activity measurement, may allow for approval if the medication can show that a child functions better. The use of surrogate study endpoints can be particularly important in pediatric studies, in which long-term outcomes relevant to children are difficult to assess. Such surrogate endpoints can be clinical, physiological or biochemical. Personalized medicine, computer modeling and simulation, and registry studies may also be of future value in the pediatric population.

“With continuous development of new medications, and a lack of data on outcomes with those currently available, there is a need to formulate new tools for pediatric clinical trials and alternative study designs to overcome identified barriers,” the authors write. “Open communication between clinician-scientists and the FDA is a key strategy for success. This paper highlights the need for cooperation in describing the current state and direction of pediatric research and the regulatory environment as it pertains to the development of cardiovascular drugs.” 

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Pulmonary Hypertension and Venous Thromboembolism, CHD & Pediatrics and Quality Improvement, Heart Failure and Cardiac Biomarkers, Pulmonary Hypertension

Keywords: Biological Markers, Cardiovascular Agents, Cardiovascular Diseases, Child, Growth and Development, Health Policy, Heart Diseases, Hypertension, Pulmonary, Infant, Life Expectancy, Mustelidae, Pediatrics, Randomized Controlled Trials as Topic, Registries, Research Design, Research Personnel, United States Food and Drug Administration


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