Supplementary file 1_Can patient self-evaluation of functional status be used for evaluation of impairment of motor function in Guillain-Barré syndrome? Mapping clinician- and patient-reported outcomes in a phase 3 study of eculizumab in Japan.docx

Background and purposeGuillain-Barré syndrome (GBS) is an autoimmune neurological disorder characterized by muscle weakness. In clinical trials, treatment benefit and disease severity are typically measured using clinician-reported outcome measures like the Hughes Functional Grading Scale (HFGS). However, patient-reported outcome measures, such as the Rasch-built Overall Disability Scale (R-ODS) may provide additional insight into the patient experience during treatment. In this study, exploratory analyses of clinical trial data were performed to investigate how existing clinician-reported outcomes and patient-reported outcomes can help to assess disease progression by providing an accurate measurement of functional status.
MethodsData were collected as part of a phase 3 study to assess the safety and efficacy of eculizumab in patients in Japan with severe GBS. The association between HFGS score and R-ODS total centile score (linear measure of limitations; 0, most severe activity and social participation limitations and 100, no limitations) was assessed using the Spearman rank-order correlation coefficient. Threshold values of R-ODS total centile score that could differentiate between patients with an HFGS score of ≤ 1 and > 1 were determined using receiver-operating characteristic curve analyses and mapping (Rasch measurement theory). A triangulation approach was used to establish a proposed value for R-ODS total centile score equivalent to an HFGS score of ≤ 1 or > 1.
ResultsOverall, 57 patients were included in this analysis. These exploratory analyses revealed good correlation between R-ODS total centile and HFGS scores. Using the Rasch model, mapping of HFGS to R-ODS scores showed a good fit. Evaluation of the R-ODS threshold that could approximate the functional motor symptom categories based on HFGS (score of 0 or 1) revealed a range of values from 60 to 80. Based on a trial sample, a threshold of 60 was found to have 100% sensitivity and 87% specificity at week 4, and 93.8% sensitivity and 77.8% specificity at week 24.
ConclusionThis study established thresholds for the R-ODS total centile score that could approximate classification of functional impairment in GBS based on the HFGS score. Given that the R-ODS reflects the patient perspective, it may be used to capture a more complete picture of GBS severity.