Associate professor Copenhagen Centre for Regulatory Science, University of Copenhagen Copenhagen, Denmark
Background: The European Paediatric regulation (EPR) was set in place to facilitate the development of medicines for the paediatric population. Its success in doing so has been questioned, particularly regarding cancer treatments for children. The main regulatory tool in the EPR to achieve its goals is the Paediatric Investigation Plans (PIPs), agreed upon between the sponsor and the European Medicines Agency Paediatric Committee (PDCO).
Objectives: The objective of this study is to map the trajectories of all PIPs in oncology approved by PDCO since its initiation in 2007 until December 2022 and to assess if these PIPs resulted in paediatric cancer indications.
Methods: We identified all PDCO decisions for paediatric product development for an oncology indication since the initiation of PDCO in August 2007 until December 2022, excluding PIPs only relating to diagnosis or supportive care. All agreed PIPs were followed until compliance check, conversion to full waiver, discontinuation, or end of study (Dec. 2022). We also identified anti-cancer products approved through the centralised procedure and retrieved information about paediatric cancer indications in the approved product from the Summary of Product Characteristics. Anti-cancer products were linked to the original PIPs, to analyse how many PIPs had resulted in paediatric indications.
Results: From 2007 until 2022 PCDO has issued a decision on paediatric development or waiver for 345 applications for anti-cancer drugs. For 197 of them, a full waiver was granted, three decisions were refusals of applications, and for the remaining 145 a partial waiver or full PIP was agreed upon. Among these, five were modified to a waiver, and nine were discontinued within the study period. Adolescents were included in all PIPs, children were included in 94% of PIPs, infants and toddlers in 76%, and newborns in 29% of PIPs. At end of study 53 of 131 PIPs had reached the agreed date of completion, and 18 (33%) of these had received a positive compliance check. Fifty-nine anti-cancer products with a PIP were granted MA (covered by 68 individual PIPs), with a median time since MA of 7.5 years 20 of these products had one or more paediatric cancer indications as a result of 22 individual PIPs. One of these products was subsequently withdrawn their MA. Eleven paediatric cancer indication was granted to products with completed PIPs, for additional 9 products whose PIPs had not yet received a positive compliance check.
Conclusions: For the majority of anti-cancer products paediatric development is waived, and only 33% of PIPs are completed despite having exceeded the agreed completion date. Completed PIPs resulted in indication paediatric indications in 60% of the cases. In addition a few non-completed PIPs also resulted in approved paediatric indications.
