Ethical challenges in paediatric clinical trials in multiple sclerosis.

Children and adolescents with multiple sclerosis (MS) are reported to show high rates of relapse early in the course of the disease as well as cognitive deterioration over time. Immunomodulatory therapies developed for adult MS patients are currently the standard first-line agents for most paediatric MS patients. Available data indicate that the three interferon-beta preparations and glatiramer acetate are safe and well tolerated in children and adolescents with MS, and provide preliminary indications of efficacy in terms of relapse rate reduction. However, these treatments are only partly effective and their routes of administration can be bothersome, particularly for children. Emerging therapies for MS offer promise for improved disease control and long-term clinical outcome, with the advantage of an oral administration for some of them. The future approval of these new medications requires clinical trial consideration of such therapies in the paediatric population. Many of these new agents carry a higher risk for serious adverse events with increased toxicity and still undefined long-term side effects. There are ethical issues as well as issues related to feasibility that must be borne in mind when planning investigation trials for new pharmacological agents in the paediatric population, including immunological maturity, key period of exposure to numerous community-acquired infections, neurodevelopmental factors, in addition to short-term and long-term age-related toxicities. Furthermore, the lack of a large enough paediatric MS population worldwide limits some designs and the feasibility of participation in all the studies. Emerging new therapies have the potential to optimize the care of both paediatric and adult patients with MS. Future treatment trials in children and adolescents with MS will require a multicentre design, definition and selection of key outcome measures, and identification of the most promising therapies. Risks versus benefits of each specific treatment should be weighed and comprehensively discussed.