June 25, 2014

International Pediatric MS Study Group's Recommendations on Clinical Trials Published

Background: Childhood MS

MS is usually considered to be a disease of young adults. However, a number of studies indicate that between 2.7% and 5% of individuals with MS are diagnosed much earlier in life. The majority of children with MS are between 10 and 17 years old, but MS has been seen as early as two years of age.

Children with MS typically experience a relapsing-remitting course, characterized by clearly defined attacks (called relapses) ofsymptoms that subside (remit) either on their own or with treatment. Duringthe periods of remission, there are no new symptoms and no progression of the disease. Other forms of MS are almost never seen in children.

The cause of childhood MS remains unknown, just as it is for adults. More problematically there are limited studies on how or if disease-modifying treatments work for children with MS. International collaboration and implementation of multi-centre studies focusing on MS in children are urgently needed to narrow the knowledge gap and increase treatment options.

International Pediatric MS Study Group:

To meet this need, the International Pediatric MS Study Group (IPMSSG) was created in April 2006.  It is made up of more than 150 physicians and researchers as well MS Society representatives around the world. Led by the Multiple Sclerosis International Federation (MSIF), the IPMSSG is working to enhance healthcare, education, and research in pediatric MS and related demyelinating disorders of the central nervous system. Several prominent Canadian MS clinicians and researchers who have each contributed to understanding and treatment of pediatric MS are involved with this voluntary group: Dr. Brenda Banwell, Dr. Amit Bar-Or, Dr. Ruth Ann Marrie, and Dr. Ann Yeh.

Today, many new therapies for adult MS are on the horizon. Recent legislation in the United States and Europe now mandates that pediatric studies be carried out whenever a new treatment is anticipated for use in children. The IPMSSG recognizes that pediatric clinical trials pose many challenges including a limited number of children to study and a lack of available clinical trial data. The January 2012 meeting was an occasion to address these challenges and discuss the members’ views on evaluating emerging therapeutic options for children with MS.

The IPMSSG Clinical Trials Summit:

The IPMSSG clinical trials summit workshop, “Towards Therapeutic Trials in Pediatric Multiple Sclerosis,” in January 2012, brought 69 attendees together, including:

  • IPMSSG members
  • Medical and academic experts in MRI, clinical trial design, therapeutics and neuropsychology
  • Representatives from US Food and Drug Administration (FDA), European Medicines Agency (EMA) and Health Canada
  • Pharmaceutical company representatives
  • Staff leadership from the National MS Society, MSIF, MS Society of Canada and Italian MS Society

Goals and Outcomes:

The primary objective was to discuss feasibility, ethical challenges, and most effective methods for pediatric clinical trials of new medications in MS. Prior to the meeting, 7 expert working groups were convened to focus on key areas:

  • Clinical outcome measures
  • Cognitive outcome measures
  • MRI outcome measures
  • Clinical trial design
  • Pediatric pharmacology
  • Safety and biological mechanisms
  • Long-term outcome registries

During the meeting, delegates weighed in on the benefits and challenges associated with conducting clinical trials in pediatric MS patients. They affirmed that clinical trials are necessary to assess short- and long-term safety of therapies and to gain accurate information on dose and treatment length for children. They noted the current lack of information on disease patterns in pediatric MS and the lack of earlier pediatric clinical trials for current therapies commonly used in adults.

There was discussion on clinical, MRI and cognitive outcomes in pediatric trials and consensus points were identified. They agreed that measuring the frequency of relapses would be a primary outcome of phase III trials and that implementing a long-term drug safety registry reporting on serious adverse effects in children with MS would be useful. Finally, they explored the potential role of an international pediatric MS clinical trials network, which would ensure consistency among protocols, aid development of better trials everywhere to prevent exposure of children to trials that could fail to produce knowledge, and serve as a resource for past and ongoing trials.

The formal report on the meeting and its recommendations was published in an issue of Neurology this March. This publication is the world’s most widely read peer-reviewed journal for the neurology community—and will therefore serve professionals in pediatric MS research and care around the world.


Outcomes from the IPMSSG Clinical Trials Summit as well as future work conducted by the pediatric group will ensure consistency in future pediatric MS clinical trials. The summit was a unique opportunity for experts in the field as well as industry and regulatory stakeholders to come together and share knowledge in an area that requires further research and understanding. The development of MS clinical trials for the younger MS patient population exclusively will point to vital information on dose, safety, efficacy, and long-term benefits of current and emerging MS therapies.

Chitnis T et al. International Pediatric MS Study Group Clinical Trials Summit. Neurology 2013 Mar 19; 80(12):1161-1168