Extent of Safety Database in Pediatric Drug Development: Types of
Assessment, Analytical Precision, and Pathway for Extrapolation through
On-Target Effects
Pediatric patients should have access to medicines that have been
appropriately evaluated for safety and efficacy. Given this goal of revised
labelling, the adequacy of the pediatric clinical development plan and
resulting safety database must inform a favorable benefit-risk assessment for
the intended use of the medicinal product. While extrapolation from adults can
be used to support efficacy of drugs in children, there may be a reluctance to
use the same approach in safety assessments, wiping out potential gains in
trial efficiency through a reduction of sample size. To address this
reluctance, we explore safety review in pediatric trials, including factors
affecting these data, specific types of safety assessments, and precision on
the estimation of event rates for specific adverse events (AEs) that can be
achieved. In addition, we discuss the assessments which can provide a benchmark
for the use of extrapolation of safety that focuses on on-target effects.
Finally, we explore a unified approach for understanding precision using
Bayesian approaches as the most appropriate methodology to describe/ascertain
risk in probabilistic terms for the estimate of the event rate of specific AEs