1. 1 Impediments to Early Initiation of Pediatric Studies in a Clinical Oncology Drug Development Program A Large Pharmaceutical Company Perspective  Corporate Considerations –Need to demonstrate a “pathway to registration” in a large-market indication  Drug Development Considerations –Elucidation of the adult safety profile and MTD usually facilitates subsequent pediatric development –Formulation requirements (IV and oral)  IP and Liability Considerations –MTA and CRADA processes

2. 2 Impediments to Early Initiation of Pediatric Studies in a Clinical Oncology Drug Development Program A Large Pharmaceutical Company Perspective  Regulatory Considerations –Burden of proof required for registration in the context of a very limited study population –Integration of new agents into complex treatment regimens  Isolation of therapeutic effect and safety profile –Standard definitions of DLT may not be optimal for pediatric populations –Pediatric Exclusivity restrictions  Inclusion of all pediatric age-groups in early clinical trials  Constraints on using “old data” that may otherwise be adequate to support new labeling

3. 3 Impediments to Early Initiation of Pediatric Studies in a Clinical Oncology Drug Development Program A Large Pharmaceutical Company Perspective Clinical Resource Considerations  Competition for a scarce resource –Overall availability of eligible patients for pediatric phase I studies –Success of the pediatric cooperative groups Prioritization of new drugs within COG Prioritization of new drugs within COG  Validity of preclinical pediatric tumor models

4. 4 Overcoming Impediments Early Initiation of Pediatric Drug Development  Lower the regulatory hurdles to pediatric registration if and when this can be justified -Prerequisite of the adequately powered randomized trial? -Define “clinical benefit” in children? -Establish acceptable surrogate endpoints for use in pediatric trials?  Increase access to eligible patients – Promote increased industry-COG-NCI collaboration  Ex-US enrollment initiatives  Prioritization of scarce patient resources  Expedite initiation and execution of trials  Jointly funded development (MTA and CRADA)  Maintain and expand incentive programs for early pediatric oncology drug development – Unique issues and needs