1. Application of the 1998 Pediatric Rule to Oncology Steven Hirschfeld, MD PhD CDR U.S. Public Health Service Medical Officer Division of Oncology Drug Products Center for Drug Evaluation and Research Food and Drug Administration

2. Brief History n Pediatric therapeutic development has never been as thorough or robust as adult therapeutic development n Many therapies are administered to children without adequate study n Many therapies are not made available for pediatric study until after adult marketing studies are completed

3. Pathways to Development Conventional n Pre-clinical ---> Adult - - - > Pediatric Possible n Pre-clinical ---> Adult + Pediatric n Pre-clinical ---> Pediatric - - -> Adult

4. FDA Pediatric Initiatives n 1994 Rule established principle of extrapolation of efficacy data from adult population to pediatric population if certain conditions were met n 1997 Exclusivity Extension in FDAMA

5. 1998 Pediatric Rule n Mandates pediatric studies if the indication for an application under review can be found in children n Applies to drugs and biologicals n If the indication does not apply to children, then a waiver can be granted n Does not specifically address extrapolation of efficacy- raises issue of “Are studies warranted?” n Does not delay development for adult indication

6. Question for committee How should the 1998 Rule be applied for solid tumors and central nervous system malignancies?

7. Goals n Recommendations for adult indications that should trigger the Pediatric Rule n Recommendations for adult indications that should be waived from compliance n Recommendations for general principles that may used to apply the Pediatric Rule

8. Example of a principle n If a lesion is necessary for establishing or maintaining the malignant phenotype and if a therapy is directed against that lesion, then studies in tumors where the lesion occurs and has the same critical role are warranted