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Original research
Measurement properties of the Inclusion Body Myositis Functional Rating Scale
  1. Sharfaraz Salam1,
  2. Tara Symonds2,
  3. Helen Doll2,
  4. Sam Rousell2,
  5. Jason Randall2,
  6. Lucy Lloyd-Price2,
  7. Stacie Hudgens3,
  8. Christina Guldberg4,
  9. Laura Herbelin5,
  10. Richard J Barohn5,
  11. Michael G Hanna1,
  12. Mazen M Dimachkie6,
  13. Pedro M Machado1,7
  14. On behalf of Members of the Arimoclomol in IBM Investigator Team of the Neuromuscular Study Group
  1. 1Department of Neuromuscular Diseases, University College London, London, UK
  2. 2Clinical Outcomes Solutions Ltd, Folkestone, UK
  3. 3Clinical Outcomes Solutions Ltd, Tucson, Arizona, USA
  4. 4Orphazyme Aps, Copenhagen, Denmark
  5. 5Department of Neurology, University of Missouri, Columbia, Missouri, USA
  6. 6Department of Neurology, University of Kansas City Medical Center, Kansas City, Missouri, USA
  7. 7NIHR University College London Hospitals Biomedical Research Centre, University College London Hospitals National Health Service (NHS) Trust, London, UK
  1. Correspondence to Professor Pedro M Machado; p.machado{at}ucl.ac.uk

Abstract

Objectives To evaluate the validity, reliability, responsiveness and meaningful change threshold of the Inclusion Body Myositis (IBM) Functional Rating Scale (FRS).

Methods Data from a large 20-month multicentre, randomised, double-blind, placebo-controlled trial in IBM were used. Convergent validity was tested using Spearman correlation with other health outcomes. Discriminant (known groups) validity was assessed using standardised effect sizes (SES). Internal consistency was tested using Cronbach’s alpha. Intrarater reliability in stable patients and equivalence of face-to-face and telephone administration were tested using intraclass correlation coefficients (ICCs) and Bland-Altman plots. Responsiveness was assessed using standardised response mean (SRM). A receiver operator characteristic (ROC) curve anchor-based approach was used to determine clinically meaningful IBMFRS change.

Results Among the 150 patients, mean (SD) IBMFRS total score was 27.4 (4.6). Convergent validity was supported by medium to large correlations (rs modulus: 0.42–0.79) and discriminant validity by moderate to large group differences (SES=0.51–1.59). Internal consistency was adequate (overall Cronbach’s alpha: 0.79). Test–retest reliability (ICCs=0.84–0.87) and reliability of telephone versus face-to-face administration (ICCs=0.93–0.95) were excellent, with Bland-Altman plots showing good agreement. Responsiveness in the worsened group defined by various external constructs was large at both 12 (SRM=−0.76 to −1.49) and 20 months (SRM=−1.12 to −1.57). In ROC curve analysis, a drop in at least two IBMFRS total score points was shown to represent a meaningful decline.

Conclusions When administered by trained raters, the IBMFRS is a reliable, valid and responsive tool that can be used to evaluate the impact of IBM and its treatment on physical function, with a 2-point reduction representing meaningful decline.

Trial registration number NCT02753530.

  • INCL BODY MYOSITIS
  • MUSCLE DISEASE
  • NEUROMUSCULAR
  • RANDOMISED TRIALS
  • RHEUMATOLOGY

Data availability statement

Data are available on reasonable request. Data sharing requests can be submitted after 1 year following publication of the main study results, to the corresponding authors, who will provide a data access request form. Data sharing requests will be considered by the Trial Steering Committee on a case-by-case basis, and data will be shared if the request is considered reasonable, of scientific interest, and legally and ethically possible.

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Data availability statement

Data are available on reasonable request. Data sharing requests can be submitted after 1 year following publication of the main study results, to the corresponding authors, who will provide a data access request form. Data sharing requests will be considered by the Trial Steering Committee on a case-by-case basis, and data will be shared if the request is considered reasonable, of scientific interest, and legally and ethically possible.

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Footnotes

  • X @pedrommcmachado

  • MMD and PMM contributed equally.

  • Correction notice Since this paper first published, affiliation 7 has been updated and PMM and MMD have been listed as joint last authors.

  • Collaborators Members of the Arimoclomol in IBM Investigator Team of the Neuromuscular Study Group

    Anthony A. Amato MD (Department of Neurology, Brigham & Women's Hospital, Boston, MA, USA); Emma Ciafaloni MD (Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA); Miriam Freimer MD (Department of Neurology, The Ohio State Wexner Medical Center, Columbus, OH, USA; Summer B. Gibson MD (Neuromuscular Division, University of Utah School of Medicine, Salt Lake City, UT, USA); Sarah M. Jones MD (Department of Neurology, University of Virginia, Charlottesville, VA, USA); Todd D. Levine MD (Department of Neurology, HonorHealth, Phoenix, AZ, USA); Thomas E. Lloyd MD (Departments of Neurology and Neuroscience, Johns Hopkins University, Baltimore, MD, USA); Michael P. McDermott PhD (Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA); Tahseen Mozaffar MD (Division of Neuromuscular Disorders, University of California, Irvine, Orange, CA, USA); Aziz I. Shaibani (Nerve & Muscle Center of Texas, Baylor College of Medicine, Houston, TX, USA); Matthew Wicklund (Department of Neurology, University of Texas Health Science Center at San Antonio, TX, USA).

  • Contributors The first draft of the manuscript was written by SS and PMM. All authors critically reviewed and commented on each draft of the manuscript. All authors approved the final manuscript for submission. PMM and MMD contributed to this manuscript equally and are joint last authors. PMM is the guarantor for this study.

  • Funding The arimoclomol trial was cofunded by a 4-year FDA Office of Orphan Products Development grant (grant/award no. R01FD004809) and Orphazyme A/S (grant/award no. N/A).

  • Disclaimer The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health.

  • Competing interests SS is supported by a UCL Queen Square Institute of Neurology & Cleveland Clinic London MPhil/PhD Neuroscience Fellowship. TS, HD, SR, JR, LL-P and SH are employees of Clinical Outcomes Solutions, a health research consultancy that was paid to conduct the measurement properties analyses reported in this study. CG was an employee of Orphazyme A/S, the pharmaceutical company that funded the measurement properties analyses reported in this study. LH has no disclosures to report. RJB has received funding from the FDA Office Orphan Products Development grant for his role in the arimoclomol trial. MGH receives research funding from the Medical Research Council UK and has previously acted as a consultant for Novartis and for Orphazyme A/S. MMD serves or recently served as a consultant for Abata/Third Rock, Abcuro, Amicus, ArgenX, Astellas, Cabaletta Bio, Catalyst, CNSA, Covance/Labcorp, CSL-Behring, Dianthus, Horizon, EMD Serono/Merck, Ig Society, Janssen, Medlink, Octapharma, Priovant, Sanofi Genzyme, Shire Takeda, TACT/Treat NMD, UCB Biopharma, Valenza Bio and Wolters Kluwer Health/UpToDate; MMD also received research grants or contracts or educational grants from Alexion/AstraZeneca, Alnylam Pharmaceuticals, Amicus, Argenx, Bristol-Myers Squibb, Catalyst, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, The Myositis Association, and UCB Biopharma/RaPharma. PMM has received honoraria from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme Pfizer, Roche and UCB.

  • Provenance and peer review Not commissioned; externally peer reviewed.