Regulatory Science Symposium: Bringing Drugs and Biologics to Market - Session 5: "Pediatric Clinical Trials and Study Plans"

Competencies: Pediatric Clinical Trials, Clinical Trial Endpoints, Decentralized Clinical Trials, Regulatory Compliance, Regulatory Science, Clinical Research and Regulations, Clinical Trials, Regulatory and Quality Sciences, Clinical Trial Quality

Course Syllabus/Topics

1. History and Key Developments
   1. First documented study in 1796
   2. Establishment of Pediatric labelling in the 1970s
   3. FDA Modernization Act in 1997
   4. The Best Pharmaceuticals for Children Act (BPCA) in 2002 and the Pediatric Research Equity Act (PREA) in 2003
2. Pediatric and Adult Clinical Trials
   1. Smaller sample size
   2. Adult trials are more likely to be randomized than pediatric trials
   3. Ethical Standards vary
3. Endpoints
   1. Assessment endpoints modified for children
   2. Quality of life is becoming a major endpoint for both adult and pediatric trials
      1. e.g.: Vision tests for children may involve naming shapes over letters
4. Regulations
   1. FDA's classification of pediatric populations into four age groups: neonates, infants, children, and adolescents
   2. Adults provide informed consent while children provide assent, requiring signatures from parents or legal guardians
5. PREA
   1. Enacted in 2003, mandates pediatric assessments for new drug and biologic applications unless waived or deferred
6. BPCA
   1. Enacted in 2002, provides incentives such as additional patent exclusivity for conducting pediatric studies on patented drugs
   2. Created Pediatric Advisory Committee to provide guidance
   3. Results and data are submitted to the FDA for consideration
7. Written Requests
8. Approvals
9. Accelerating Approval Process
   1. Leverage FDA’s fast-track, breakthrough therapy, accelerated approval, and priority review programs
10. IRB
    1. `They evaluate risk-benefit ration
    2. Important to include members with pediatric experience
    3. Pediatric studies classified into different risk categories, from minimal risk to greater than minimal risk with or without prospect of direct benefit
11. Pediatric Study Plans (PSP)
    1. Regulatory development plans required by the FDA to ensure new drugs and biologics are appropriately studied in children
    2. Requirements for PSP submission according to PREA
    3. iPSP submitted no later than 60 days after end of Phase 2
    4. Include new active ingredients, indications, dosages, dosing regimens, and routes of administration
12. Exemptions and Waivers
    1. Orphan drug designations exempt from PREA requirements
    2. Full or partial waivers granted for certain conditions such as evidence suggesting the drug will be ineffective or unsafe in children
13. Deferrals
14. PSP Components
    1. Overview of the disease, the drug or biologic, planned pediatric studies (e.g., pharmacokinetic and efficacy/safety studies), pediatric formulation development, and timelines
15. FDA Compliance
    1. FDA reviews study plans and maintains a public database of PREA post-market requirements
    2. Non-compliance can result in FDA non-compliance letters and impact a site's reputation
16. Formulations
17. Australia - Regulatory Differences
    1. Therapeutic Goods Administration (TGA) is the FDA equivalent
    2. Sponsors to complete a pediatric development program form included in Module 1.10 of the CTD
18. Challenges
    1. Safety concerns, ethical considerations, and recruitment difficulties
    2. Age-appropriate dosage forms
19. Informed Consent Challenges
20. Decentralized Clinical Trials (DCTs)
    1. Offers potential solutions with remote sessions, home health visits, telehealth and digital data collection
    2. eConsent
21. Key Takeaways
22. CHLA - video

Acknowledgements:
Accompanying text created by: Mahita Parasa, Student Worker; Karen Manrique, Program Administrator, SC CTSI (kmanriqu@usc.edu)