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 5 decades, pediatric cancer
drug development has faced biological, societal and economic challenges,
due to low prevalence patient population, concerns related to ethical
issues and perception of increased liability in testing drugs in
children, and lack of financial incentives.
Two laws passed by the U.S. Congress, the Pediatric Research Equity Act
(PREA) [3], which provides the requirement for pediatric studies,
and the Best Pharmaceuticals for Children Act (BPCA) [4], which
provides the incentive of additional exclusivity for products of
sponsors who voluntarily 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 under PREA 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 trials 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 trials can vary greatly according to the disease indications.
As a result, the requirements of oncology drug trials in WR vary
greatly. As BPCA has been the only legislative initiative that impacts
pediatric cancer drug development, more recent WRs were issued for
products early in development to accelerate pediatric assessment and
requirements for studies included in the WRs were contingent upon the
results of a preceding study.
The objective of this research is to identify, review, and evaluate all
the written requests (WRs) for pediatric clinical trials of new drug
products for 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.