Adopted guidelines reflect a harmonised European approach to a specific scientific issue and should reflect the most recent scientific knowledge. However, whilst EU regulations are mandatory for all member states and EU directives must be followed by national laws in line with the directive, EMA guidelines do not have legal force and alternative approaches may be taken, but these obviously require more justification. This new series of the BJCP, developed in collaboration with the EMA, aims to address this issue by providing an annotated version of some relevant EMA guidelines and regulatory documents by experts. Hopefully, this will help in promoting their diffusion and in opening a forum for discussion with our readers.
BACKGROUNDFor a medicine to be authorised, clinical efficacy and safety should be established, usually through robust and relevant clinical trial data.The conduct of paediatric clinical trials is, however, fraught with hurdles related to operational practicalities, regional differences in standards of care, lack of standard of care, cultural expectations, and ethical challenges. Additional complexities relate to the rarity of the diseases and gaps in knowledge about the pathophysiology and epidemiology of diseases across paediatric age subsets, particularly in neonates and children less than 2 years of age. These challenges lead to concern internationally that despite the implementation of the legal framework in the United States and from the first 10 years of the Paediatric Regulation in the EU, depending on the disease and age of the child, 50% to 80% of children are still treated off-label. [1][2][3] Often, drug development proceeds in adults first, and once approved in adults, medicines are prescribed off-label to children, out of need, long before an evidence base establishes efficacy, safety, and appropriate dosing. This is particularly of relevance for the youngest age ranges, as typically, for these groups, dosages are more difficult to predict, and both the disease and the response to the drug may differ, to at least some extent. For the last decades, when a medicine is not authorised for children, paediatric clinical practice will rely on