OBJECTIVES: Transition from RRMS to SPMS is difficult to diagnose. Here, we describe methodology for developing a screening tool that can help physicians to diagnose SPMS early. METHODS: Tool will be developed along 3 steps: Quantitative research: A retrospective cross-sectional study to describe differentiating characteristics between SPMS and late RRMS patients using Adelphi Real World database. 2791 MS patient record forms from 125 neurologists (US) are available. Key variables will include demographics, MS history, treatment history, daily activities, symptoms and clinical characteristics including MRI activity. Patients will be stratified based on EDSS and disease duration into: Early RRMS (control group), Late RRMS and Early SPMS. A multivariate regression analysis will identify the significant predictors of patient classification as ‘Late RRMS’ or ‘Early SPMS’ by physician. Qualitative research: (1) Open-ended qualitative interviews of patients (16 each in the US and Germany—8 RRMS and 8 SPMS/country) and treating clinicians (8/country) to identify and characterize key differentiating features of these two MS phenotypes. (2) Integrating interviews with quantitative research to draft the tool. (3) Use of draft version by physicians treating SPMS patients. (4) Cognitive debriefing with physician. Tool validation: Sensitivity and specificity will be validated against reference tests in a 12Month prospective observational study in patients with late RRMS and SPMS after the implementation of the tool. RESULTS: Data collected will be used to generate a paper version of the tool that will track the disease experience of late RRMS patients periodically (relapse and recovery, symptoms, quality of life). After validating the paper version, an electronic version will be considered. A calculator will be added to the tool to predict likelihood of patient progression to SPMS. CONCLUSIONS: Such a validated tool is expected to support physicians in more accurate and timely identification of SPMS patients to provide optimized clinical intervention.