A review on the role of extrapolation as basis for paediatric marketing authorization applications of medicines in the EU.

Aims: For new medicines, drug companies obtain regulatory approval on the strategy to generate evidence in the paediatric population, which can be supported by extrapolation of evidence obtained in a reference population. This study investigated whether paediatric marketing authorization applications (PMAAs) supported by extrapolation based on exposure-matching were more successful-i.e. approval of the targeted paediatric population-and efficient-i.e. duration of the drug development-compared to PMAAs not supported by extrapolation.

Methods: Data was extracted from completed paediatric investigation plans (PIPs), associated drug labels and public assessment reports published on the European Medicines Agency website. Assessment reports were evaluated to assess whether PMAAs were supported by extrapolation based on exposure-matching. Wilcoxon rank-sum tests were used to compare PMAAs supported and not supported by extrapolation based on exposure-matching for outcomes of interest.

Results: Exposure-matching supported the benefit/risk assessment of 39.6% of the PMAAs. Targeted and approved minimum age of the paediatric population were comparable for PMAAs where extrapolation based on exposure-matching supported the benefit/risk assessment (2.0 vs. 2.0 years, P-value = .72), but not for PMAAs not supported by extrapolation (0.2 years vs. 0.5 years, P-value = .05). Completion of drug development was 5.4 years vs. 4.3 years (P = .04) in PMAAs supported by extrapolation based on exposure-matching compared to those not supported by extrapolation, respectively.

Conclusions: PMAAs supported by extrapolation based on exposure-matching succeeded more often in obtaining marketing approval in the targeted paediatric population than PMAAs not supported by exposure-matching, but were also less efficient.