Introduction
A 1968 editorial article in the Journal of Pediatrics referred to
children as “therapeutic orphans” [1] to express the frustration
of many clinicians over the lack of pediatric prescribing information
for approved drugs [2]. For the past decades, pediatric cancer drug
development has faced biological, societal and economic challenges, such
as low prevalence patient population, concerns relating to ethical
issues and perception of increased liability of testing drugs in
children, companies not interested in pediatric studies and many more.
The Pediatric Research Equity Act (PREA) [3], which requires
studies, and the Best Pharmaceuticals for Children Act (BPCA) [4],
which provides the incentive of additional exclusivity for products of
sponsors who conduct requested studies in the pediatric population, were
enacted in 2003 and 2002 respectively, following the initial legislative
provision for exclusivity in 1997 to correct this serious deficiency in
drug development for young patients.
The requirement for pediatric evaluation of most oncology products
developed for adult cancers is generally waived, because the common
cancers which occur in adults and which are the focus of drug discovery
and development efforts are never or very rarely seen in children or
because the indication or drug had been granted orphan designation. PREA
therefore has had no impact on pediatric anticancer drug development.
Pediatric studies for labeling updates are largely done through BPCA by
the fulfillment of a Written Request (WR), issued by the FDA. Because
cancers in the pediatric and adult populations generally do not share
the same biology, natural history and disease progression, full
extrapolation from adults is unlikely, and requirements for the
pediatric studies can vary greatly according to the disease indications.
As a result, the requirements of oncology drug studies in WR can vary
greatly.
The objective of this research is to identify, review, and evaluate all
the written requests (WRs) for pediatric clinical trials regarding solid
tumor and hematologic malignancies that were initially issued by the
Food and Drug Administration between the dates January 1, 2001, and
December 31, 2019. The authors from the Office of Biostatistics (OB),
Office of Clinical Pharmacology (OCP) in CDER and Oncology Center of
Excellence (OCE) have collaborated to review the content of WRs issued
to sponsors for oncology drugs and biologics.