Performing clinical drug trials in children with a rare disease

Over the past 50 years, the advancements in medical and health research have radically changed the epidemiology of health conditions in neonates, children, and adolescents; and clinical research has on the whole, moved forward. However, large sections of the pediatric community remain vulnerable and underserved, by clinical research. One reason for this is the fact that most pediatric diseases are also rare diseases (i.e., they fit the EU definition of a rare condition, by affecting no more than 5 in 10,000 individuals), and indeed the majority of conditions under this umbrella heading are in fact much rarer, affecting fewer than 1 in 100,000. Rare pediatric diseases incur particular challenges, both in terms of actually conducting clinical trials but also planning trials (and indeed, stimulating the preclinical research and knowledge generation necessary to embark on clinical trials in the first place). The pediatric regulation and orphan regulation (covering rare diseases) were introduced to address the complexities in research and development of medicines specifically for children and for people living with a rare disease, respectively. The regulations have been reasonably effective, particularly in areas where adult and pediatric diseases overlap, driving the development of more pediatric medicines; however, challenges still remain, often exacerbated by the rarity of the diseases. These include issues around trial planning, the need for more innovative methodologies in smaller populations, significant delays in trial start up and recruitment, recruitment issues (due to small populations and the nature of the conditions), lack of endpoints, and scarce data. This chapter will discuss some of the major challenges in delivering trials in pediatric rare diseases while also assessing current and future solutions to address these.