title: Progression on the Multiple Sclerosis Functional Composite in multiple sclerosis: what is the optimal cut-off for the three components?
abstract: For the Timed 25-Foot Walk (T25FW) and 9-Hole Peg Test (9HPT), components of the Multiple Sclerosis Functional Composite (MSFC), cut-off points of 20% change have previously been defined as meaningful endpoints of functional decline. Recently, however, a 15% change of MSFC components was introduced. The objective of this study was to determine optimal cut-offs for all MSFC components to indicate clinical disease progression in a primary progressive (PP) multiple sclerosis (MS) population. T25FW, 9HPT and the Paced Auditory Serial Addition Test (PASAT) were performed in 161 patients with PPMS with a 2-year interval. Absolute and relative differences in test scores were calculated. For each cut-off point of relative change, proportions of patients who progressed (deterioration beyond cut-off value) and improved (improvement beyond cut-off value) were calculated. Further, we calculated the ratio of 'improved' versus 'progressed' patients. Line graphs were created indicating: percentage progressed patients, percentage improved patients, and ratio of improved versus progressed patients. The optimal cut-off was determined by searching the cut-off point with the lowest ratio of improved versus progressed patients, while at the same time capturing a substantial amount of progression. For both T25FW and 9HPT, the ratio between patients that improved and worsened clearly decreased between the cut-offs of 15% and 20%. For the PASAT, the ratio between patients improved and worsened was persistently poor. In conclusion, a cut-off of 20% for both T25FW and 9HPT has a better signal-to-noise ratio than lower values (e.g. 15%) and is therefore preferable for the assessment of disease progression. No satisfactory cut-off point for the PASAT could be determined.
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. l.bosma@vumc.nl
authors.forename: L V A E
authors.initials: LV
authors.lastname: Bosma
authors.forename: J J
authors.initials: JJ
authors.lastname: Kragt
authors.forename: L
authors.initials: L
authors.lastname: Brieva
authors.forename: Z
authors.initials: Z
authors.lastname: Khaleeli
authors.forename: X
authors.initials: X
authors.lastname: Montalban
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: M
authors.initials: M
authors.lastname: Tintoré
authors.forename: B M J
authors.initials: BM
authors.lastname: Uitdehaag
mesh_terms: D003071:Cognition; D004185:Disability Evaluation; D018450:Disease Progression; D005060:Europe; D006225:Hand / Q000503:physiopathology; D006801:Humans; D009048:Motor Skills; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013997:Time Factors; D016138:Walking