Original article| Volume 57, 103438, January 2022

Determining the minimal important change of the 6-minute walking test in Multiple Sclerosis patients using a predictive modelling anchor-based method

Published:November 30, 2021DOI:


      • The minimally important change (MIC) for improvement of the 6-minute walking test is 19.7 m in patients with Multiple Sclerosis (MS).
      • The MIC for deterioration of the 6-minute walking test is 7.2 in the same patients.
      • The MICs can help physicians and therapist to evaluate their treatment.



      The minimal important change (MIC) of the 6-minute walk test (6MWT) is not clear for patients with Multiple Sclerosis (MS), hampering treatment evaluation. The aim of our study was therefore to determine the MIC of the 6MWT in MS patients.


      MS patients did the 6MWT using the instruction to walk at comfortable speed twice with approximately one year in between. After the second 6MWT they completed 3-point anchor question. The MICadjusted with a 95% confidence interval (CI) was calculated with the predictive modelling method with bootstrapping.


      118 MS patients (mean age 48.2 years, 23.7% men) were included between September 2018 and October 2019. Mean 6MWT distance was 468 ± 112 m at baseline and 469 ± 115 m one year later. Twenty-three (19.5%) patients answered their walking distance improved, 43 (36.4%) answered it worsened. A MICadjusted for improvement of 19.7 m (95%CI 9.8–30.9 m) was found, and for deterioration of 7.2 m (95%CI -3.3–18.2 m).


      Using the most sophisticated statistical method, the MICadjusted of the 6MWT in MS patients was 19.7 m for improvement, and 7.2 m for deterioration. This knowledge allows physiotherapists and physicians to evaluate if their treatment has led to a meaningful improvement for their MS patients or if walking of their patients has deteriorated.



      CI (confidence interval), COSMIN (COnsensus-based Standards for the selection of health Measurement Instruments), EDSS (Expanded Disability Status Scale), ICC (intraclass correlation coefficient), MIC (Minimal Important Change), MS (Multiple Sclerosis), 6MWT (6-Minute Walking Test), SD (standard deviation), ROC (receiver operating curve)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Multiple Sclerosis and Related Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • ATS
        Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test.
        Am. J. Respir. Crit. Care Med. 2002; 166: 111-117
        • Baert I.
        • Freeman J.
        • Smedal T.
        • et al.
        Responsiveness and clinically meaningful improvement, according to disability level, of five walking measures after rehabilitation in multiple sclerosis: a European multicenter study.
        Neurorehabil. Neural Repair. 2014; 28: 621-631
        • Bohannon R.W.
        • Crouch R.
        Minimal clinically important difference for change in 6-minute walk test distance of adults with pathology: a systematic review.
        J. Eval. Clin. Pract. 2017; 23: 377-381
        • Buoite Stella A.
        • Morelli M.E.
        • Giudici F.
        • et al.
        Comfortable walking speed and energy cost of locomotion in patients with multiple sclerosis.
        Eur. J. Appl. Physiol. 2020; 120: 551-566
        • Compston A.
        • Coles A.
        Multiple sclerosis.
        Lancet. 2008; 372: 1502-1517
        • Gijbels D.
        • Alders G.
        • Van Hoof E.
        • et al.
        Predicting habitual walking performance in multiple sclerosis: relevance of capacity and self-report measures.
        Mult. Scler. 2010; 16: 618-626
        • Goldman M.D.
        • Marrie R.A.
        • Cohen J.A.
        Evaluation of the six-minute walk in multiple sclerosis subjects and healthy controls.
        Mult. Scler. 2008; 14: 383-390
        • Halliday S.J.
        • Wang L.
        • Yu C.
        • et al.
        Six-minute walk distance in healthy young adults.
        Respir. Med. 2020; 165105933
        • Hartung H.P.
        • Graf J.
        • Aktas O.
        • et al.
        Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 - continuity and change.
        Curr. Opin. Neurol. 2019; 32: 327-337
        • Holden M.K.
        • Gill K.M.
        • Magliozzi M.R.
        • et al.
        Clinical gait assessment in the neurologically impaired. Reliability and meaningfulness.
        Phys. Ther. 1984; 64: 35-40
        • Learmonth Y.C.
        • Dlugonski D.D.
        • Pilutti L.A.
        • et al.
        The reliability, precision and clinically meaningful change of walking assessments in multiple sclerosis.
        Mult. Scler. 2013; 19: 1784-1791
        • Mokkink L.B.
        • Terwee C.B.
        • Patrick D.L.
        • et al.
        The COSMIN study reached international consensus on taxonomy, terminology, and definitions of measurement properties for health-related patient-reported outcomes.
        J. Clin. Epidemiol. 2010; 63: 737-745
        • Morard M.D.
        • Besson D.
        • Laroche D.
        • et al.
        Fixed-distance walk tests at comfortable and fast speed: potential tools for the functional assessment of coronary patients?.
        Ann Phys Rehabil Med. 2017; 60: 13-19
        • Pearson M.
        • Dieberg G.
        • Smart N.
        Exercise as a therapy for improvement of walking ability in adults with multiple sclerosis: a meta-analysis.
        Arch. Phys. Med. Rehabil. 2015; 96 (e7): 1339-1348
      1. R. Development Core, (2012) Team: R: A language and Environment For Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria.

        • Terluin B.
        • Eekhout I.
        • Terwee C.B.
        • et al.
        Minimal important change (MIC) based on a predictive modelling approach was more precise than MIC based on ROC analysis.
        J. Clin. Epidemiol. 2015; 68: 1388-1396
        • Terluin B.
        • Eekhout I.
        • Terwee C.B.
        The anchor-based minimal important change, based on receiver operating characteristic analysis or predictive modelling, may need to be adjusted for the proportion of improved patients.
        J. Clin. Epidemiol. 2017; 83: 90-100
        • Terwee C.B.
        • Peipert J.D.
        • Chapman R.
        • et al.
        Minimal important change (MIC): a conceptual clarification and systematic review of MIC estimates of PROMIS measures.
        Qual. Life Res. 2021;
        • Weller D.
        • Lörincz L.
        • Sutter T.
        • et al.
        Fampridine-induced changes in walking kinetics are associated with clinical improvements in patients with multiple sclerosis.
        J. Neurol. Sci. 2020; 416116978
        • Woaye-Hune P.
        • Hardouin J.B.
        • Lehur P.A.
        • et al.
        Practical issues encountered while determining Minimal Clinically Important Difference in Patient-Reported Outcomes.
        Health Qual. Life Outcomes. 2020; 18: 156