author(s)
Amjad Khan

abstract
The availability of safe, effective, and age-appropriate medications for children has been limited by specific scientific, ethical, legal, and operational challenges that pediatric drug development faces. Over the past 20 years, regulatory incentives and methodological improvements—such as pediatric extrapolation, adaptive and platform trial designs, model-informed drug development (MIDD), and the use of real-world data (RWD)—have started to address some of these gaps, but significant obstacles persist. This systematic review not only highlights new opportunities and suggestions to accelerate the development of safe and effective pediatric treatments but also summarizes research on the barriers faced in pediatric drug development. Key findings include ongoing issues related to off-label use and drug availability, difficulties in trial design and recruitment for small and diverse pediatric populations, and ethical restrictions on sampling; however, progress has been made through advances in extrapolation guidance, MIDD, innovative trial platforms, and international regulatory harmonization.