The Charité MS Initiative
In 2016, the Charité launched an initiative for patients with multiple sclerosis (MS). Its goal is to improve the quality of clinical MS trials and to increase patient relevance. After discussions with the Federal Chancellery, the Federal Ministry of Health and pharmaceutical companies, the Charité developed a concept for achieving this goal. The concept was based on the US Forum for Collaborative HIV Research. As a neutral institution, the initiative now connects patient representatives, MS experts, authorities and institutions in the healthcare system as well as research-based pharmaceutical companies in order to submit joint proposals at an early stage for the design of studies on drug therapies. The initiative also pays special attention to patient-relevant endpoints and the development of studies and registries to gain better insights into the benefits and harms of MS drugs in the post-approval period.
Background:
Multiple sclerosis is the most common autoimmune disease of the central nervous system, affecting more than 200,000 people in Germany. They suffer from impaired vision and sensation as well as restrictions in coordination and even paralysis. MS is usually diagnosed between the ages of 20 and 40 and it is not curable so far. In 85 to 90 percent of patients, the disease starts with relapsing neurological deficits, which usually disappear completely or partially after weeks or months. After years or decades, a transition into a chronic-progressive course often occurs with a gradual deterioration of the neurological condition. Since the development of the first immunotherapy in 1995, numerous substances have been approved for the immunomodulatory treatment of MS, with the aim of reducing the number of relapses. Since then, the therapeutic landscape has expanded considerably. It now includes not only a pure relapse prevention approach, but also individualized medical care.
Certain symptoms and consequences of the disease are highly relevant for patients, but today’s clinical studies rarely attach importance to these symptoms. This was also pointed out in a study (1) by a working group of the Drug Commission of the German Medical Association (AkdÄ), the Charité University Hospital Berlin, and the Institute for Quality and Efficiency in Health Care (IQWiG). The analysis of 29 drug approval (“pivotal”) phase III trials on disease course-modifying/immunomodulating drugs for the treatment of MS showed that the patient perspective and thus symptoms such as fatigue (i.e. tiredness and increased exhaustibility) or health-related quality of life were generally not taken into account. In contrast, biological indicators and endpoints of imaging procedures with unclear relevance for the severity of the disease were routinely investigated.
Future studies on MS should attribute greater importance to the immediate experience of patients with MS, for example by focusing more on patient-reported outcomes (PROs). The working group developed recommendations for the improvement of clinical studies on MS. These recommendations were also based on the findings of the MS Initiative. It became clear that for those affected it is particularly important whether symptoms such as fatigue, depression, cognitive impairment, pain, spasticity, sleep disorders or loss of vision increase. These and other patient-relevant endpoints should be considered more in clinical studies. Sinje Gehr, Project Head of the Charité MS Initiative, states: “With our recommendations, we want to make a contribution to the improvement of care for patients with MS”. Prof. Dr. Friedemann Paul, Scientific Director of the Experimental and Clinical Research Center (ECRC), a joint facility of the Charité and Max Delbrück Center for Molecular Medicine (MDC), notes: “If we design future studies in such a way that they are more closely orientated to the patients’ needs, we will obtain study results that are more likely to enable us to provide patients with more targeted and individualized medical care.” In addition, methodologically sound data on long-term adverse effects or benefits of the drugs were mostly lacking because they were mainly investigated in one- or two-year drug approval studies.
The MS Initiative has succeeded in bringing together the relevant stakeholders in clinical MS studies so that different views and perspectives could be exchanged. Such exchange formats can make a valuable contribution to forming biomedical research more patient-relevant. The article now published in the EPMA Journal shows the results of this intensive long-term cooperation.
References:
(1) Gehr S, Kaiser T, Kreutz R, Ludwig WD, Paul F: Suggestions for improving the design of clinical trials in multiple sclerosis — results of a systematic analysis of completed phase III trials. EPMA Journal (2019) 10: 425. doi.org/10.1007/s13167-019-00192-z.