For Researchers

Treatment of patients with Relapsing-Remitting Multiple Sclerosis (RRMS) relies on clinical and radiological disease activity, the benefit-risk profile of drug therapy, and preferences of patients and physicians. However, there is limited guidance supporting evidence-based personalized decision-making on how to adapt the increasingly available highly efficient immunosuppressive treatments to treat patients as little as possible but as much as necessary; ensuring no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events and improved care.

The overarching objective of MultiSCRIPT is to establish a learning system in which accumulating data will enable the continuous generation of new hypotheses on how treatment and care strategies can be further personalized to treat patients as little as possible but as much as necessary at the right time, i.e., ensuring no evidence of disease activity (with more sensitive biomarkers such as for example sNfL), while achieving better patient-relevant outcomes, and improved care by better informing shared decision-making. The learning system will be evolutionary with continuous adaptive processes of data collection, analysis, interpretation, hypothesis testing, and clinical implementation embedded within the SMSC.

The Swiss MS Cohort Study (SMSC) since 2012 has developed a critical expertise in the standardization and integration of high-quality clinical, imaging and biomarker assessments across 8 Swiss leading MS centers in >1600 MS patients. The SMSC offers a unique opportunity to establish a platform trial to continuously assess multiple new intervention.

A learning cycle consists of three steps, which are described below.

Step 1: Development of a new intervention to be assessed

The development of new interventions and definition of hypotheses to be tested will be based on systematic reviews, key experts’ opinions in the field and evidence continuously emerging from the SMSC from previous MultiSCRIPT cycles or other related projects within RC2NB. For an intervention to be assessed within MultiSCRIPT a consensus needs to be reached on how this intervention should be implemented and translated into usual care if proven beneficial

Delphi survey will be an integral part of the platform structure ensuring informed decision making in the scientific process of generating new hypothesis and developing new treatment guidelines.

Step 2: Trial conduct

Patients will be allocated to the new treatment and/or care management compared with the usual care at the time of the randomization. For more details see Cycle 1 below.

Step 3: Close-out of the learning cycle

Based on the trial results and/or emerging evidence in the scientific literature, the Trial Steering Committee will decide whether the tested intervention should be implemented in usual care as a new treatment and/or care management. If it becomes the usual care and it would then be used as the control in subsequent learning cycles against which future new interventions will be tested. Such future new interventions may include, for example, the addition of a new biomarker to monitor disease activity, or new or modified diagnostic, therapeutic or care management interventions.

Key features of MultSCRIPT:

  • Platform for pragmatic randomized trials
  • Continuous evaluation embedded in usual care
  • Personalized treatment strategies for patients with MS
  • Patient-relevant outcomes

CYCLE 1: Intensive biomarker monitoring using sNfL

The first cycle will be a comparison of an intensive biomarker monitoring strategy using the serum neurofilament light chain (sNfL) biomarker with the current usual care. Extensive research has been conducted on sNfL within the SMSC. sNfL is associated with future disease activity and is increasingly used as a treatment response marker. We plan to include 915 RRMS patients. In the intervention group, 6-monthly monitoring of sNfL will together with information on relapses, disability and magnetic resonance imaging (MRI) inform more personalized treatment decisions (e.g., escalation or de-escalation) supported by pre-specified treatment guidelines established through a Delphi survey. In the control group, patients will receive usual care with their usual 6- or 12-monthly visits. Two primary outcomes will be used: 1) Evidence of disease activity (EDA3: occurrence of relapses, disability worsening (Expanded Disability Status Scale (EDSS)), or MRI activity) and 2) quality of life (MQoL-54) using 24-month follow-up.

The intervention will be considered superior to usual care if either more patients have no EDA3, or their health-related quality of life increases. Secondary outcomes will include relapses, disability worsening, MRI activity, serious adverse events and economic outcomes.

Data collection will be embedded within the SMSC using established trial-level quality procedures. The first cycle will last 4.5 years.