Application of the 1998 Pediatric Rule to Oncology

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

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Clinical Research

• Recorded for at least 2400 years
• Children were often the first patients for new
  procedures and interventions
• Among the founding principles of modern food and
  drug regulation was protecting children

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Brief History

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

4
Pathways to Development

• Conventional
• Pre-clinical ---gt Adult - - - gt Pediatric
• Possible
• Pre-clinical ---gt Adult Pediatric
• Pre-clinical ---gt Pediatric - - -gt Adult

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FDA Pediatric Initiatives

• 1994 Rule established principle of extrapolation
  of efficacy data from adult population to
  pediatric population if certain conditions were
  met
• 1997 Exclusivity Extension in FDAMA

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Exclusivity Extension

• No linkage between adult and pediatric
  indications
• Voluntary program
• Realized in response to an FDA Written Request
• May be approached in oncology by a Phase I and a
  portfolio of Phase II or pilot studies
• Over 20 Written Requests issued

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1998 Pediatric Rule

• Mandates pediatric studies if the indication for
  an application under review can be found in
  children and therapeutic advance or widespread
  use are anticipated
• Applies to drugs and biologicals
• If the indication does not apply to children,
  then a waiver can be granted
• Does not specifically address extrapolation of
  efficacy- raises issue of Are studies
  warranted?
• Does not delay development for adult indication

8
Question for committee

• The circumstances that would trigger the 1998
  Rule would be anticipation of a therapeutic
  advance in an indication that applies for both
  adults and children. How should the 1998 Rule be
  applied once it has been invoked?

9
Goals

• Recommendations for considerations in designing
  dose finding studies, particularly when adult
  data are available
• Recommendations for considerations in using adult
  data for the design and interpretation of
  pediatric safety and efficacy studies

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Example of a principle

• 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