Horacio Plotkin, vice president and medical lead, Rare Disease and Pediatric Center of Excellence, discusses the challenges researchers face when conducting studies in the pediatric space and talks about the impact of PPD’s Pediatric Investigator Network (PIN), a network of 14 pediatric centers of excellence established to share scientific thinking, improve pediatric study design and communicate knowledge across the international research community.
What do you think are the biggest challenges researchers currently face in working with pediatric populations?
The biggest challenge today is perhaps that most drugs used in the pediatric population are prescribed “off-label.” Economic reasons (the pediatric market may be too small to theoretically justify expensive clinical studies), ethical misconceptions and strategic reasons (e.g., concerns that children show adverse events not seen in adults) often guide decisions about pediatric drug development.
A particularly challenging group is newborn patients. There are several reports on the lack of research on medications in newborns with respect to safety, effectiveness or dose. Meanwhile, infants admitted to a neonatal intensive care unit may receive up to 60 medications in their first month of life, in many cases used off-label. The Best Pharmaceuticals for Children Act of 2002 and the Pediatric Research Equity Act of 2003 both “worked” and as a result 651 drugs in the U.S. have new or revised labeling for pediatric patients, but they did not particularly help newborns. There are many specific technical and ethical challenges to conducting clinical research in this population, but clinical studies are definitely warranted.
Why is it important to advance child-centric research in the drug development industry?
Children are not small adults. There are many obvious differences in terms of metabolism, body surface, the ability to take medicines and even preferences with regards to the taste of medicines. In many cases, adult formulations (large pills) are not suitable for children. Additionally, safety and efficacy may be very different in growing individuals.
Dosing is often done by body weight in pediatric patients, as opposed to fixed doses in adults. In many cases, dividing the adult dose by 75 (the weight in kilograms for an average adult) to calculate the dose per kilogram is not appropriate. Therefore, the conduct of dosing studies specific for growing individuals is paramount.
Other important considerations are the comfort and trust of pediatrics patients once they are enrolled, which are very important for retention in clinical studies.
How is PPD’s Pediatric Investigator Network working to overcome these challenges and advance pediatric drug development?
The Pediatric Investigator Network (PIN), a network of 14 pediatric centers of excellence established to share scientific thinking, is actively involved not only in study execution, but also in study protocol development. Through real-life experience in pediatric centers of excellence, members of the PIN can advise sponsors of clinical trials on practical matters involving pediatric patients, including aspects such as hospitalization and discharge criteria, admissible blood sampling volumes, feasibility of endpoints, assent language, etc.
Why is building community within the pediatric research space especially important?
In this day and age, collaborative work among medical centers to potentiate experience and expertise is the rule. Exchange of ideas and good practices lead to better patient care and clinical studies, particularly in the pediatric environment, where off-label and empirical use of medications are common. In that sense, all members of the network can benefit from others’ experience, which improves the safety and efficacy of treatments.
Horacio Plotkin is vice president and medical lead of the Rare Disease and Pediatric Center of Excellence.