Abstract
Objective: Pediatric studies for new biological agents are mandated by recent legislation, necessitating careful thought to evaluation of emerging multiple sclerosis (MS) therapies in children with MS. Challenges include a small patient population, the lack of prior randomized clinical trials, and ethical concerns. The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research.
Methods: The Steering Committee of the International Pediatric MS Study Group identified key focus areas for discussion. A total of 69 meeting attendees were assembled, including 35 academic experts. Regulatory and pharmaceutical representatives also attended, and provided input, which informed academic expert consensus decisions.
Results: The academic experts agreed that clinical trials were necessary in pediatric MS to obtain pharmacokinetic, safety and efficacy data, and regulatory approval allowing for greater medication access. The academic experts agreed that relapse was an appropriate primary outcome measure for phase III pediatric trials. An international standardized cognitive battery was identified. The pros and cons of various trial designs were discussed. Guidelines surrounding MRI studies, pharmacokinetics, pharmacodynamics, and registries were developed. The academic experts agreed that given the limited subject pool, a stepwise approach to the launch of clinical trials for the most promising medications is necessary in order to ensure study completion. Alternative approaches could result in unethical exposure of patients to trial conditions without gaining knowledge.
Conclusion: Consensus points for conduct of clinical trials in the rare disease pediatric MS were identified amongst a panel of academic experts, informed by regulatory and industry stakeholders.
GLOSSARY
- ADS=
- acute demyelinating syndrome;
- AE=
- academic expert;
- ARR=
- annualized relapse rate;
- BPCA=
- Best Pharmaceuticals Act for Children;
- CAL=
- cumulative active lesion;
- CIS=
- clinically isolated syndromes;
- EDSS=
- Expanded Disability Status Scale;
- EMA=
- European Medicines Agency;
- FDA=
- US Food and Drug Administration;
- IPMSSG=
- International Pediatric MS Study Group;
- MS=
- multiple sclerosis;
- MSIF=
- MS International Federation;
- NMSS=
- National MS Society;
- PIP=
- pediatric investigation plan;
- PK=
- pharmacokinetic;
- PREA=
- Pediatric Research Equity Act
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received July 27, 2012.
- Accepted December 10, 2012.
- © 2013 American Academy of Neurology
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