Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disorder of the central nervous system. It is associated with a variable, large number of symptoms which cause significant disability and reductions in health-related quality of life. The Expanded Disability Status Scale (EDSS) is a clinician reported outcome (ClinRO) measure and is the most widely used disability rating scale in MS. Common to many ClinROs, due to the subjective nature of assessment it is important to train physicians in the assessment and scoring of the EDSS and to put in place other mechanisms to minimize the intra- and inter-rater variability.
One approach to help standardize the rating and scoring of the EDSS was the development of the “Neurostatus” – a standardized approach that has been generally accepted as gold standard in most pharmaceutical clinical trials, including successful regulatory drug applications. Conducting an assessment using the Neurostatus-EDSS includes calculating seven functional system scores (Visual, Brainstem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral); assessing an ambulation score to determine walking capacity (distance possible and use of assistance); and calculating the resulting “EDSS step” using the Neurostatus-EDSS calculation table. The scoring of the individual functional systems is derived from the assessment and rating of up to 120 individual signs and symptoms.
Signant Health has worked with the owners of the Neurostatus to implement an electronic version of the Neurostatus-EDSS (eEDSS) to limit inconsistencies, inaccuracies, conflicting recordings and miscalculations that may adversely affect the reliability of EDSS scores reported using the pen-and-paper version of the standardized assessment.
The eEDSS uses a touch-screen tablet computer for electronic capture of the results of the neurological examination including the Neurostatus subscores, functional system scores, the ambulation score and the resulting calculation of the EDSS step. An internal algorithm provides real-time feedback, based on the Neurostatus definitions, indicating inconsistencies in the scoring of parts of the neurologic examination, functional systems, ambulation score, and EDSS. The final decision on the correct scores remains with the physician, who can overrule the algorithm. The eEDSS is enhanced further through centralized expert rating quality assessment. This is performed by researchers at University Hospital Basel (UHB) to provide additional feedback to the raters to improve consistency and accuracy of rating between and within assessors.
Dr Marcus D’Souza, University Hospital Basel (UHB), and colleagues from UHB, Novartis and Signant Health (formerly CRF Health) recently published experience data on the use of the eEDSS obtained from two phase III MS trials.
The study reported that 40.1% of initial rater assessments contained miscalculations of the functional system or ambulation or the overall EDSS score. In addition, the study showed that 14.8% of EDSS scores were changed by the site raters as a result of the automated and central-rater checking process employed by the solution. Because the EDSS typically represents the primary endpoint in MS clinical trials, this electronic method including automated logic checks and central rater quality assurance is a useful tool to increase standardization, consistency, and reliability of EDSS assessments in clinical MS trials.
Read the full article, published in Multiple Sclerosis Journal, 7 May 2019.