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. 2023 Apr 26;18(4):e0283669.
doi: 10.1371/journal.pone.0283669. eCollection 2023.

Determining minimal clinically important differences in the North Star Ambulatory Assessment (NSAA) for patients with Duchenne muscular dystrophy

Vandana Ayyar Gupta  1 , Jacqueline M Pitchforth  1 , Joana Domingos  1 , Deborah Ridout  2   3 , Mario Iodice  1 , Catherine Rye  1 , Mary Chesshyre  1 , Amy Wolfe  1 , Victoria Selby  1 , Anna Mayhew  4 , Elena S Mazzone  5 , Valeria Ricotti  1   3 , Jean-Yves Hogrel  6 , Erik H Niks  7   8 , Imelda de Groot  9 , Laurent Servais  6   10   11 , Volker Straub  4 , Eugenio Mercuri  5   12 , Adnan Y Manzur  1 , Francesco Muntoni  1   3 ; iMDEX Consortium and the U.K. NorthStar Clinical Network
Affiliations

Determining minimal clinically important differences in the North Star Ambulatory Assessment (NSAA) for patients with Duchenne muscular dystrophy

Vandana Ayyar Gupta et al. PLoS One. .

Abstract

The North Star ambulatory assessment (NSAA) is a functional motor outcome measure in Duchenne muscular dystrophy (DMD), widely used in clinical trials and natural history studies, as well as in clinical practice. However, little has been reported on the minimal clinically important difference (MCID) of the NSAA. The lack of established MCID estimates for NSAA presents challenges in interpreting the significance of the results of this outcome measure in clinical trials, natural history studies and clinical practice. Combining statistical approaches and patient perspectives, this study estimated MCID for NSAA using distribution-based estimates of 1/3 standard deviation (SD) and standard error of measurement (SEM), an anchor-based approach, with six-minute walk distance (6MWD) as the anchor, and evaluation of patient and parent perception using participant-tailored questionnaires. The MCID for NSAA in boys with DMD aged 7 to 10 years based on 1/3 SD ranged from 2.3-2.9 points, and that on SEM ranged from 2.9-3.5 points. Anchored on the 6MWD, the MCID for NSAA was estimated as 3.5 points. When the impact on functional abilities was considered using participant response questionnaires, patients and parent perceived a complete loss of function in a single item or deterioration of function in one to two items of the assessment as an important change. Our study examines MCID estimates for total NSAA scores using multiple approaches, including the impact of patient and parent perspective on within scale changes in items based on complete loss of function and deterioration of function, and provides new insight on evaluation of differences in these widely used outcome measure in DMD.

Trial registration: ClinicalTrials.gov NCT02780492.

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Conflict of interest statement

E.H.Niks report grants from Spieren voor Spieren, Duchenne Parent Project, ZonMW, AFM and PPMD. He has been site principal investigator for clinical trials conducted by BioMarin, GSK, Eli Lilly, Santhera Pharmaceuticals, Italfarmaco SpA, Roche Pharma, Reveragen, NS Pharma, Fibrogen, Sarepta, Alexion, Janssen and Argnx outside the submitted work. He also reports ad hoc consultancies for BioMarin, Summit, PTC therapeutics, WAVE Life Sciences, Edgewise, Epirium Bio, Janssen, Sarepta and Regenxbio. All reimbursements were received by the LUMC. No personal financial benefits were received. I.de Groot has received consulting and education fees from PTC Therapeutics, Santhera, Biomarin/Prosensa. J-Y.Hogrel has received consulting fees from Biogen, Sarepta, Minoryx and Roche. L.Servais has received consulting fees from Roche, Biogen, Avexis, Cytokinetics, Sarepta, Biomarin, Santhera, Servier, Biophytis and Dynacure. He is coordinating natural history studies funded by Valerion, Dynacure and Roche. A.Mayhew has received consulting fees from Roche, Novartis (Avexis), Biogen, Rehenxbio, PTC, BMS/Roche, Sarepta, Italfarmaco, Pfizer, Summit, Catabasis, Santhera, Vision, Mallinckrodt, Lysogen, Modis and Wave. V.Straub received speaker honoraria from Sanofi Genzyme and has participated in advisory boards for Audentes Therapeutics, Biogen, AveXis, Pharmaceuticals, Pfizer, Roche, Sanofi Genzyme, Sarepta Therapeutics, Summit Therapeutics and Wave Therapeutics. V.Ricotti is co-founder, EVP, CMO of DiNAQOR, and served as a consultant for Solid Biosciences and Antisense Therapeutics. F.Muntoni reports grants from Sarepta, grants from Wave, grants from PTC Therapeutics, personal fees from Avexis, Roche, Pfizer, Dyne Therapeutics, Sarepta, outside the submitted work. M.Chesshyre has had the costs associated with attending a conference (including travel, accommodation, conference fee, food and drink) funded by PTC Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Scatter plot of annual changes in 6MWD vs NSAA total score (non-overlapping changes).
Fig 2
Fig 2. Preventing loss of function.
Distribution of participant responses for significant change as minimum number of items on NSAA for preventing loss of activity (i.e., preventing a change in score from 1 to 0). The x-axis represents minimum number of sub items for which prevention of loss of function was meaningful for a parent (red) and for a patient with DMD (blue).
Fig 3
Fig 3. Maintaining function.
Distribution of participant responses for significant change as minimum number of items on NSAA for maintenance of function (i.e., preventing a change in score from 2 to 1). The x-axis represents minimum number of sub items for which maintaining the activity was meaningful for a parent (red) and for a patient with DMD (blue).
Fig 4
Fig 4. Participant responses for minimum requirements for participating in a clinical trial lasting 2 years based on improvement of motor function, slowing the decline of motor function, or stopping the decline of motor function of items in the NSAA.
NA = missing response.
See this image and copyright information in PMC

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References

    1. Mercuri E, Bönnemann CG, Muntoni F. Muscular dystrophies. Lancet. 2019. Nov 30;394(10213):2025–2038. doi: 10.1016/S0140-6736(19)32910-1 . - DOI - PubMed
    1. Moat SJ, Bradley DM, Salmon R, Clarke A, Hartley L. Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK). Eur J Hum Genet. 2013. Oct;21(10):1049–53. Epub 2013 Jan 23. doi: 10.1038/ejhg.2012.301 . - DOI - PMC - PubMed
    1. Reinig AM, Mirzaei S, Berlau DJ. Advances in the Treatment of Duchenne Muscular Dystrophy: New and Emerging Pharmacotherapies. Pharmacotherapy. 2017. Apr;37(4):492–499. Epub 2017 Mar 10. doi: 10.1002/phar.1909 . - DOI - PubMed
    1. McDonald CM, Campbell C, Torricelli RE, Finkel RS, Flanigan KM, Goemans N, et al.. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017. Sep 23;390(10101):1489–1498. Epub 2017 Jul 17. doi: 10.1016/S0140-6736(17)31611-2 . - DOI - PubMed
    1. Charleston JS, Schnell FJ, Dworzak J, Donoghue C, Lewis S, Chen L, et al.. Eteplirsen treatment for Duchenne muscular dystrophy: Exon skipping and dystrophin production. Neurology. 2018. Jun 12;90(24): e2146–e2154. Epub 2018 May 11. Erratum in: Neurology. 2018 Sep 25;91(13):637. doi: 10.1212/WNL.0000000000005680 . - DOI - PubMed

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