Background Pediatric anticancer drug development has numerous challenges. The PREA and the BPCA were passed to address the deficiency in pediatric drug development in general. Until recently, the requirement for pediatric evaluation of most oncology products has been waived, because children typically do not have the same type of cancers which occur commonly in adults or the indication or drug had been granted orphan designation. PREA therefore had no impact. Pediatric studies for labeling updates are largely done through BPCA by a Written Request, issued by FDA. Because pediatric and adult populations do not share the same biology, natural history, or disease progression, there are limited opportunities to extrapolate adult efficacy and safety to the pediatric population. The requirements for the pediatric studies have varied greatly over time. Procedure In this study, we searched WRs that were issued by the FDA since 2001. We found 40 such requests issued for oncology drugs and biologics which had been accepted by sponsors. Results Clinical trials included in 23 of the WRs have been concluded, 19 have resulted in exclusivity, and 3 drugs that were studied have been approved for use in pediatric populations. Herein we present the spectrum of WRs from a regulatory, study design, dosing, formulation, analysis plan, evidential standard of efficacy and safety perspective. Conclusions This provides information on requests in the past nearly 20 years and studies completed. As WRs are the anchor of pediatric cancer development for the time being, this can potentially provide insight on how pediatric cancer drug development may change in the future.

Background Pediatric anticancer drug development has numerous challenges. Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA), has been put forth to address the deficiency in pediatric drug development in general. Until recently, the requirement for pediatric evaluation of most oncology products for adult cancers was waived, because children typically do not have adult-type cancers or the indication or drug had been granted orphan designation. PREA therefore had no impact. Pediatric studies for labeling updates are largely done through BPCA by a Written Request (WR), issued by FDA. Because pediatric and adult populations do not share the same biology, natural history, or disease progression, there are limited opportunities to extrapolate adult information to pediatric. The requirements for the pediatric studies can vary greatly. Procedure In this study, we searched WRs that were issued by the FDA since 2001. We found 42 requests for pediatrics in oncology drugs and biologics. Results Studies included in 25 of the WRs have concluded, 18 have been given exclusivity, and 4 drugs have been approved for use in pediatric populations. The current status of the WRs are presented from regulatory, study design, dosing, formulation, analysis plan, evidential standard of efficacy and safety. Conclusions This would serve the purposes to study what has been requested over the years and what have been completed in response to the requirements. We consider this to be the anchor of pediatric cancer development for current stage and can potentially provide insight on how pediatric cancer drug development would change for the future years.