Richard C. “Mort” Wasserman, MD, MPH Professor of Pediatrics, University of Vermont

1. Current Status of U.S. Pediatric Clinical Research Infrastructure:A Snapshot of Multi-Site Research Capacity Richard C. “Mort” Wasserman, MD, MPH Professor of Pediatrics, University of Vermont Director, Pediatric Research in Office Settings (PROS) American Academy of Pediatrics Work done with Eric Slora, PhD, Donna Harris, MA, and Alison Bocian, MS. Supported by the American Academy of Pediatrics

2. Presentation Objectives • Explain focus on multi-site pediatric clinical research infrastructure • Provide a snapshot of pediatric clinical research network infrastructure • Provide a snapshot of pharmaceutical trials infrastructure • Offer some conclusions relevant to pediatric drug & medical device development

3. Rationale for Focus on Multi-Site Clinical Research Infrastructure • Pediatric clinical research often must recruit subjects from multiple sites, either because the clinical condition under study is uncommon, or because the study outcomes occur infrequently • Dictionary definition of infrastructure: “underlying foundation” or “basic framework” • Multi-site clinical research requires more of an infrastructure than single site research

4. Multi-Method Approach: Interviews • Interviews: From February-July, 2007, we interviewed 33 pediatric clinical research experts on the topic of U.S pediatric clinical research capacity • Informant list: • developed to maximize cognitive diversity • refined during recruitment according to themes emerging in the interviews • Informants’ primary and secondary areas of expertise: • academician (21) • federal official (5) • industry medical officer (8) • pediatric research network leader (10) • pediatric specialist leader (8) • pediatric clinical pharmacologist (5) • practitioner-research site director (9)

5. Multi-Method Approach:Enumerating the ExclusivelyPediatric Clinical Research Networks • Searched research network databases: IECRN & AHRQ-PBRN for exclusively pediatric networks • Identified additional networks: • Web search • Interview informants • Surveyed network contacts about past and current activities

6. Multi-Method Approach:Other Surveys • Survey of ~1,000 pediatric practitioners in PROS regarding pharmaceutical trials • Survey of 43 AAP subspecialty section and council leaders about clinical and pharmaceutical trials research among their members

7. Multi-Method Approach:Enumerating the Number of Sites in U.S. & Canada Participating in Pediatric Pharmaceutical Trials • Data from Clinicaltrials.gov • Data from FDA written requests

8. Results:Pediatric Clinical Research Networks • Types of networks (n=78) • Primary care (study topics are applicable to the general pediatric population): 22 • Specialty (study topics are pertinent to a pediatric subspecialty such as oncology, rheumatology): 36 • Disease-Specific (study topics are within a specific disease such as inflammatory bowel disease, type I diabetes): 20

9. Results:Pediatric Clinical Research Networks • Network diversity: • Longevity (range 1-50+ years) • Geography • Regional (24%): national (30%); international (41%) • Types of studies: • Diagnostic test evaluation, variety of RCTs (patient and cluster level), registry, outcomes research, pharmacokinetics, qualitative research • Core funding: NIH, MCHB, AHRQ, foundations, institutional, none! • Number of publications: (range 0 - >1000) • ~ half entertain protocols from industry for pharmaceutical trials

10. Results:Pediatric Pharmaceutical Research • Qualitative analysis of interviews • dominant theme of insufficient pediatric drug trial capacity • lack of systems for finding, incentivizing, maintaining trial sites • complexity/demands of conducting drug trials in clinical settings • lack of qualified pediatric pharmacologists and clinician investigators trained in FDA Good Clinical Practice • poorly designed drug trial protocols that discourage pediatricians and parents from participating

11. Results:Pediatric Pharmaceutical Research • Qualitative analysis of interviews • Potential solutions • Consensus-building among stakeholders to create pediatric pharmaceutical trial systems • Initiatives to train more pediatric pharmacologists and educate clinicians in Good Clinical Practice • Advocacy for high quality pharmaceutical protocols designed by scientists sensitive to pediatric issues • Pediatric and public education on the importance of pediatric pharmaceutical trials

12. Results:Enumerating the Number of Sites in U.S. & Canada Participating in Pediatric Pharmaceutical Trials • ???

13. Bottom Line • Pediatric clinical research infrastructure relevant to pediatric drug & medical device development, although excellent in some areas, is inconsistently developed and highly fragmented • This meeting is a necessary step in correcting that situation