Registering pharmaceuticals for treating children


Many pharmaceuticals have not received a license to be marketed for children. The potential paediatric market may be small, trials in children are difficult and fear of litigation deters sponsors thus many sponsors choose not to seek regitsration in this market. In consequence, many treatments are used ‘off-label’ by paediatricians. This is a far-from satisfactory state of affairs and recently the European Medicines Agency (EMEA) has moved to require sponsors developing pharmaceuticals to have Paediatric Investigation Plans (PIPs) specifically addressing the development in children[1]. The intention of this legislation is laudable. Nevertheless, there are some doubts as to what extent it can be successful. In many diseases children are a small minority of patients. Thus, any reasonably powered paediatric programme might report years after the adult programme has finished. Alternatively if a smaller programme is submitted, it is highly likely that it would fail to provide convincing proof of efficacy and safety. Thus despite having legislated a requirement for PIPs, the EMEA may find itself in exactly the same position it was before: pharmaceuticals being developed for adults and then being used off-label for children. This shows that legislation alone is not enough tackle this issue; a logical, scientific approach weighing up cost and benefits is required. In particular it needs to be decided how much further separate information is required to make a useful contribution to determining the efficacy and safety of pharmaceuticals in children whose utility in an adult population has already been established taking account of the costs involved, both monetary and in terms of delayed implementation of treatment.


This topic is one that is ripe for the application of decision analysis. For example, it seems strange that current legislation on this topic takes no quantitative account of the prevalence of conditions in paediatric populations, since this clearly must effect the time horizon of opportunity for any treatment.





1.         EMEA, Guideline on the format and content of applications for agreement or modification of a paediatric investigation plan and requests for waivers or deferrals and concerning the operation of the compliance check and on criteria for assessing significant studies, Vol. 2008/C 243/01 (2008).