Helping people with multiple sclerosis (MS) live their lives to the fullest starts with proving the safety and efficacy of drugs and interventions with robust studies. Yet clinical trials across therapy areas and indications are beset with challenges.
They can be inefficient, unrepresentative, or simply not ask the right question, all of which contributes to delays to getting the right care to the right person at the right time. And that is why International Advisory Committee on Clinical Trials in MS, a global body sponsored by ECTRIMS and the US National Multiple Sclerosis Society, is taking action.
A two-day international meeting of MS researchers from a range of disciplines, including epidemiology, biostatistics, and patient advocacy, has culminated in a series of five papers aimed at tackling some of the biggest issues facing MS researchers. Published in the Multiple Sclerosis Journal last month, the articles offer consensus recommendations on topics from driving up involvement and increasing diversity, to understanding the heterogeneity of treatment response and selecting appropriate outcome measures. We take a quick look at some of the main themes.
In the first, Improving the efficiency of clinical trials in multiple sclerosis, the authors highlight the limitations of conventional clinical trials, and argue that more novel approaches could help drive efficiency.
“Phase III clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilised a limited number of conventional designs with a high degree of success,” write the authors. However, trials for people with progressive forms of the condition and for rehabilitation therapies have been less fruitful.
This is because traditional Phase III designs, which employ strict inclusion and exclusion criteria, are limited in the types of questions that can be addressed, and who can participate. They are ill-suited to the task of testing complex treatment strategies, and come with long timelines and high price tags, the paper says.
Recent advances in clinical trial management could offer a solution. Novel designs like platform and adaptive studies allow researchers to assess multiple treatments at once, and big data analytics has enabled the generation of potentially practice-changing real-world evidence. Translating these new approaches into patient benefit, however, will require a new research infrastructure.
Among the paper’s nine recommendations is a call for “sustained funding, collaboration, and broad stakeholder engagement” to support platform trials, and for opportunities for multi-national platform trials to be explored. They also suggest the community make better use of real-world data registries to address questions such as the comparative effectiveness of specific therapies.
Hot topic elements of trial design that have received increased attention in recent years are those of diversity, inclusion, and engagement.
Enhancing diversity of clinical trial populations in multiple sclerosis points to a growing evidence base that shows that demographic characteristics, social determinants of health, health inequities, and health disparities substantially influence the general and disease-specific health outcomes of people with MS. Hypertension is more likely to be underdiagnosed among Hispanic/Latinx persons with MS than their white American counterparts, for example, while immigrants to Canada with the condition are hospitalised more often in the first year of diagnosis than long-term residents.
Such disparities can only be addressed with the use of robust evidence. Yet MS clinical trial participants do not represent all people with MS who are treated in practice, write the paper’s authors, adding that inconsistent reporting of demographic diversity hinders our understanding of the problem. They go on to recommend the use of diversity plans, community engagement and education, and biologically justified, rather than templated, eligibility criteria.
Studies and outcomes that matter[iii]
Of course, the benefits of inclusion are not limited to tackling health inequalities and understanding the efficacy of interventions in different groups. Studies that involve patients, their families, and care givers in design and execution are more likely to enrol and retain participants, measure relevant outcomes, and result in treatments and care programmes that matter to them.
“Involvement in the design enables the development of interventions that are acceptable to patients and feasible, as well as the selection of outcomes that are important to patients, enhancing future uptake in clinical practice,” write the authors of Enhancing involvement of people with multiple sclerosis in clinical trial design.
Their rapid review of patient and public involvement (PPI) in MS trials over the last five years, however, found it was lacking.
“As an international MS research community, PPI in clinical research must become part of the research process without exception if we are to maximize opportunity and impact for people living with and affected by MS,” they conclude, pointing to tools such as those developed by the European Commission-sponsored MULTI-ACT project to help researchers develop appropriate engagement plans.
People-centred, efficient research
Together, the five articles, and their practical recommendations, strive to move the needle towards a greater, more efficient, more patient-centred MS research ecosystem.
Because helping the research community improve the quality of their studies, will help the research community improve the lives of people living with MS, the world over.
- All five papers are open access. Click here for more information https://ectrims.eu/ms-clinical-trials-committee/
About the International Advisory Committee on Clinical Trials in Multiple Sclerosis
The International Advisory Committee on Clinical Trials in Multiple Sclerosis is a global body sponsored by ECTRIMS and the US National Multiple Sclerosis Society (NMSS). The Committee has been in existence for over 30 years and is composed of experts in clinical trials and clinical research in MS.
The Committee provides perspective and guidance in areas of interest to planning and implementation of clinical trials for new agents for the treatment of multiple sclerosis. It is well known for its work in developing the McDonald Diagnostic Criteria and the 1996 and 2013 clinical course descriptors for MS. The Committee works as a whole, in international meetings and consensus-building activities, or through subcommittees and task forces on specific topics.
[i] Gray, E., Amjad, A., Robertson, J., Beveridge, J., Scott, S., Peryer, G., … & Chataway, J. (2023). Enhancing involvement of people with multiple sclerosis in clinical trial design. Multiple Sclerosis Journal, 29(9), 1162-1173.
[ii] Marrie, R. A., Chataway, J., Bierer, B. E., Finlayson, M., Martinez-Lapiscina, E. H., Panagoulias, J., … & Amezcua, L. (2023). Enhancing diversity of clinical trial populations in multiple sclerosis. Multiple Sclerosis Journal, 29(9), 1174-1185.
[iii] Gray, E., Amjad, A., Robertson, J., Beveridge, J., Scott, S., Peryer, G., … & Chataway, J. (2023). Enhancing involvement of people with multiple sclerosis in clinical trial design. Multiple Sclerosis Journal, 29(9), 1162-1173.