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.