May 15, 2019
Global Agreement on Standards for Clinical Trials Involving Children and Adolescents with MS
SUMMARY: While multiple sclerosis (MS) is typically diagnosed in young adults aged 20-49, the disease also affects children and adolescents. Typically, disease modifying treatments for MS are only tested in adults, providing little information on the safety and efficacy of new treatments in children and adolescents. Regulations from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) aim to ensure that medicines for use in children are of high quality, ethically researched and authorized appropriately with evidence on use of medicines in children. As a result, there is a need to better understand when and how to involve children and adolescents in clinical trials by exploring the complex feasibility and ethical issues related to pediatric clinical trials for the development of standardized practices globally.
DETAILS: In January 2018, the International Pediatric multiple sclerosis (MS) Study Group (IPMSSG) —a group of 165 care providers, representing 44 countries, dedicated to optimizing worldwide care, education and research in pediatric MS —convened a meeting with the steering committee and key stakeholders to review and reach consensus on updated recommendations for clinical trials involving children and adolescents with MS. This meeting was sponsored by MS Society of Canada and the National MS Society (USA). The IPMSSG published their consensus recommendations in the journal Neurology.
The updated recommendations include:
- No more than one phase 3 clinical trial should be performed for the same therapeutic.
- For pediatric clinical trials with agents proven effective in adult MS, it is inappropriate to use placebos (non-active agents) as controls.
- Clinical trials (in Phase 3) in adults should consider enrollment of teenagers in some situations.
- Pediatric pharmacokinetic/pharmacodynamic (PK/PD) studies (studies that determine how drugs are absorbed and metabolized by the body) should be completed for all new agents to identify the appropriate dose in children.
- For drugs that have been well-studied in adults and have evidence-based to support their potential efficacy in children, an open-label study should be considered as sufficient for approval in pediatric MS.
- For randomized controlled trials of agents, the control could be fingolimod (or other drugs commonly used to treat pediatric MS).
- For add-on trials, the new agent could be compared to placebo, provided that other immunomodulatory therapies, such as fingolimod or others, are maintained.
- Open-label extension studies should be mandated for all clinical trials in pediatric MS populations.
- Open-label studies or registries should be designed to monitor safety in patients 12 and under.
- In the case that an open-label study is deemed insufficient for registration in pediatric MS, a short-controlled trial with an MRI primary endpoint is recommended rather than clinical endpoint.
IMPACT: These updated recommendations from the IPMSSG will help to address the need for high-quality evidence on the effectiveness of new disease modifying therapies for the optimal treatment of children and adolescents with MS.
To read the complete recommendations in the journal of Neurology, click here.