Marcus W Koch1, Jop Mostert2, Pavle Repovic2, James D Bowen2, Bernard Uitdehaag2, Gary Cutter2. 1. From the Departments of Clinical Neurosciences (M.W.K.) and Community Health Sciences (M.W.K.), University of Calgary, Canada;Department of Neurology (J.M.), Rijnstate Hospital, Arnhem, the Netherlands; Multiple Sclerosis Center (P.R., J.D.B.), Swedish Neuroscience Institute, Seattle, WA; Department of Neurology (B.U.), MS Center Amsterdam, Amsterdam University Medical Centers, the Netherlands; and Department of Biostatistics (G.C.), University of Alabama at Birmingham. mwkoch@ucalgary.ca. 2. From the Departments of Clinical Neurosciences (M.W.K.) and Community Health Sciences (M.W.K.), University of Calgary, Canada;Department of Neurology (J.M.), Rijnstate Hospital, Arnhem, the Netherlands; Multiple Sclerosis Center (P.R., J.D.B.), Swedish Neuroscience Institute, Seattle, WA; Department of Neurology (B.U.), MS Center Amsterdam, Amsterdam University Medical Centers, the Netherlands; and Department of Biostatistics (G.C.), University of Alabama at Birmingham.
Abstract
OBJECTIVE: To investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets. METHODS: Using original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations. RESULTS: In both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates. CONCLUSIONS: All investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS.
RCT Entities:
OBJECTIVE: To investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets. METHODS: Using original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations. RESULTS: In both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates. CONCLUSIONS: All investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS.
Authors: Marcus W Koch; Jop P Mostert; Jerry S Wolinsky; Fred D Lublin; Bernard Uitdehaag; Gary R Cutter Journal: Neurology Date: 2021-08-25 Impact factor: 11.800
Authors: Marcus W Koch; Jop Mostert; Pavle Repovic; James D Bowen; Jacynthe Comtois; Eva Strijbis; Bernard Uitdehaag; Gary Cutter Journal: J Neurol Date: 2022-05-16 Impact factor: 6.682
Authors: Brian C Healy; Bonnie I Glanz; Elyse Swallow; James Signorovitch; Kaitlin Hagan; Diego Silva; Corey Pelletier; Tanuja Chitnis; Howard Weiner Journal: Mult Scler J Exp Transl Clin Date: 2021-04-11
Authors: Marcus W Koch; Jop Mostert; Pavle Repovic; James D Bowen; Eva Strijbis; Bernard Uitdehaag; Gary Cutter Journal: Mult Scler Date: 2021-12-30 Impact factor: 5.855
Authors: Eva Mm Strijbis; Pavle Repovic; Jop Mostert; James D Bowen; Bernard Mj Uitdehaag; Gary Cutter; Marcus W Koch Journal: Mult Scler Date: 2022-09 Impact factor: 5.855
Authors: Anissa Kalinowski; Gary Cutter; Nina Bozinov; Jessica A Hinman; Michael Hittle; Robert Motl; Michelle Odden; Lorene M Nelson Journal: Mult Scler Date: 2021-06-08 Impact factor: 5.855
Authors: Marcus W Koch; Jop Mostert; Pavle Repovic; James D Bowen; Eva Strijbis; Bernard Uitdehaag; Gary Cutter Journal: Mult Scler Date: 2021-07-26 Impact factor: 6.312