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Multicenter Study
. 2024 Aug;31(8):e16309.
doi: 10.1111/ene.16309. Epub 2024 Apr 24.

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study

Giorgia Coratti  1   2 , Francesca Bovis  3 , Maria Carmela Pera  1   2 , Mariacristina Scoto  4 , Jacqueline Montes  5 , Amy Pasternak  6 , Anna Mayhew  7 , Robert Muni-Lofra  7 , Tina Duong  8 , Annemarie Rohwer  4 , Sally Dunaway Young  8 , Matthew Civitello  9 , Francesca Salmin  10 , Irene Mizzoni  11 , Simone Morando  12 , Marika Pane  1   2 , Emilio Albamonte  10 , Adele D'Amico  11 , Noemi Brolatti  12 , Maria Sframeli  13 , Chiara Marini-Bettolo  7 , Valeria Ada Sansone  10   14 , Claudio Bruno  12 , Sonia Messina  13 , Enrico Bertini  11 , Giovanni Baranello  4   15 , John Day  8 , Basil T Darras  6 , Darryl C De Vivo  5 , Michio Hirano  5 , Francesco Muntoni  4   15 , Richard Finkel  9 , Eugenio Mercuri  1   2 ; ISMAC group
Collaborators, Affiliations
Multicenter Study

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study

Giorgia Coratti et al. Eur J Neurol. 2024 Aug.

Abstract

Background and purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort.

Methods: The study employed two distinct methods. MDC was calculated using distribution-based approaches to consider standard error of measurement and effect size change in a population of 321 patients (176 SMA II and 145 SMA III), allowing for stratification based on age and function. MCID was assessed using anchor-based methods (receiver operating characteristic [ROC] curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12-month HFMSE could be anchored to a caregiver-reported clinical perception questionnaire.

Results: With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of -2 for type II and -4 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and -3.2 for deterioration. Furthermore, distribution-based methods uncovered varying values across age and functional status subgroups within each SMA type.

Conclusions: These results emphasize that the interpretation of a single MCID or MDC value obtained in large cohorts with different functional status needs to be made with caution, especially when these may be used to assess possible responses to new therapies.

Keywords: Hammersmith Functional Motor Scale Expanded; minimal clinically important differences; minimal detectable change; spinal muscular atrophy.

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Conflict of interest statement

G.C., M.C.P., M.Sc., J.M., A.P., A.M., R.M.L., T.D., S.D.Y., M.C., M.P., E.A., V.A.S., A.D., C.B., S.Me., E.B., G.B., and E.M. report personal fees from Biogen, Roche, Avexis, and Novartis outside the submitted work. G.C. reports personal fees from Genesis Pharma and Biologix outside the submitted work. None of the other authors has any conflict of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Receiver operating characteristic curves to discriminate improved/stable patients from the deteriorated patients for spinal muscular atrophy (SMA) type II and III. AUC, area under curve; CI, confidence interval.
See this image and copyright information in PMC

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