A Novel, Integrative Approach for Evaluating Progression in Multiple Sclerosis: Development of a Scoring Algorithm.

BACKGROUND

There is an unmet need for a tool that helps to evaluate patients who are at risk of progressing from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS). A new tool supporting the evaluation of early signs suggestive of progression in multiple sclerosis (MS) has been developed. In the initial stage, concepts relevant to progression were identified using a mixed method approach involving regression on data from a real-world observational study and qualitative research with patients and physicians. The tool was drafted in a questionnaire format to assess these variables.

OBJECTIVE

This study aimed to develop the scoring algorithm for the tool, using both quantitative and qualitative research methods.

METHODS

The draft scoring algorithm was developed using two approaches: quantitative analysis of real-world data and qualitative analysis based on physician interviews and ranking and weighting exercises. Variables that were included in the draft tool and regarded as most clinically relevant were selected for inclusion in a multiple logistic regression. The analyses were run using physician-reported data and patient-reported data. Subsequently, a ranking and weighting exercise was conducted with 8 experienced neurologists as part of semistructured interviews. Physicians were presented with the variables included in the draft tool and were asked to rank them in order of strength of contribution to progression and assign a weight by providing a percentage of the overall contribution. Physicians were also asked to explain their ranking and weighting choices. Concordance between physicians was explored.

RESULTS

Multiple logistic regression identified age, MS disease activity, and Expanded Disability Status Scale score as the most significant physician-reported predictors of progression to SPMS. Patient age, mobility, and self-care were identified as the strongest patient-reported predictors of progression to SPMS. In physician interviews, the variables ranked and weighted as most important were stability or worsening of symptoms, intermittent or persistent symptoms, and presence of ambulatory and cognitive symptoms. Across all physicians, the level of concordance was 0.278 (P<.001), indicating a low to moderate, but statistically significant, level of agreement. Variables were categorized as high (n=8), moderate (n=8), or low (n=10) importance based on the findings from the different approaches described above. Accordingly, the respective questions in the tool were assigned a weight of "three," "two," or "one" to inform the draft scoring algorithm.

CONCLUSIONS

This study further confirms the need for a tool to provide a consistent, comprehensive approach across physicians to support the early evaluation of signs indicative of progression to SPMS. The novel and comprehensive approach to develop the draft scoring algorithm triangulates data obtained from ranking and weighting exercises, qualitative interviews, and a real-world observational study. Variables that go beyond the clinically most obvious impairment in lower limbs have been identified as relevant subtle/sensitive signs suggestive of progressive disease.