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

Abstract

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.

MSProDiscuss – Entwicklung eines digitalen Tools zur standardisierten Patientenanamnese, um Progredienz bei Multipler Sklerose zu identifizieren

“…Im nächsten Schritt wurden die identifizierten Variablen hinsichtlich ihrer Relevanz für die MS-Progression und ihres Beitrages zur Pathogenese gewichtet, um den Scoring-Algorithmus des Testsystems zu entwickeln [39]. Auch hierbei wurden quantitative und qualitative Analysen kombiniert.…”

“…Die Entwicklung von MSProDiscuss wurde durch eine nicht-zweckgebundene Förderung von Novartis und durch die Kooperation mit Adelphi unterstützt und vollzog sich in vier Schritten (▶Abb. 2): Zunächst wurden die zentralen indikationsrelevanten Variablen identifiziert [21] und entsprechend ihrer Bedeutung für die MS-Progression in einen Scoring-Algorithmus integriert [39], der schließlich psychometrisch validiert wurde [40] und derzeit in Real-World-Studien erprobt wird [41,42]. und Neurologen (n = 16) zeigte sich, dass eine Reihe von Symptomen und Beeinträchtigungen mit der Krankheitsprogression assoziiert waren (Gehfähigkeit, Kognition, Gleichgewicht, Muskelschwäche, visuelle Symptome, Blasenfunktion, Fatigue).…”

“…Wegweisend für einen neuen Ansatz zur frühen SPMS Detek tion könnte die Integration verschiedener quantitativer klinischer Tests, der Krankheitsgeschichte und der qualitativen Wahrnehmungen der Patienten sein (Patient Reported Outcomes) [21,39]. Ein solcher möglichst im digitalen Format verfügbarer Ansatz sollte in der Praxis leicht implementierbar und in Echtzeit interpretierbar sein [21].…”

How to reduce the delay of diagnosing secondary progression in multiple sclerosis

“…Using quantitative and qualitative methods of its analysis, subtle signs and symptoms can be identified which are suggestive of progression to differentiate RRMS from early SPMS disease phase. 7 Variables associated with the nature of the symptoms (e.g. intermittent vs persistent, stable vs worsening) and the presence of ambulatory, mobility, and cognitive symptoms were the most significantly associated to early SPMS.…”

Multiple Sclerosis Progression Discussion Tool Usability and Usefulness in Clinical Practice: Cross-sectional, Web-Based Survey

“…The Multiple Sclerosis Progression Discussion Tool (MSProDiscuss) is a digital tool for use by health care professionals (HCPs) in clinical practice to raise awareness of the risk of progression from RRMS to SPMS through a structured interaction between HCPs and patients. MSProDiscuss aims to help physicians, in dialog with patients, to evaluate early, subtle signs suggestive of MS disease progression [ 7 ]. The tool is based on a set of weighted questions that collect structured information on disease activity (relapses or magnetic resonance imaging activity), symptoms, and impact of the patient’s overall symptoms on daily living in the previous 6 months.…”