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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study employed two distinct methods. MDC was calculated using distribution\u2010based 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\u2010based methods (receiver operating characteristic [ROC] curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12\u2010month HFMSE could be anchored to a caregiver\u2010reported clinical perception questionnaire.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of \u22122 for type II and\u2009\u22124 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and\u2009\u22123.2 for deterioration. Furthermore, distribution\u2010based methods uncovered varying values across age and functional status subgroups within each SMA type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.16309","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T08:38:13Z","timestamp":1713947893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6666-5628","authenticated-orcid":false,"given":"Giorgia","family":"Coratti","sequence":"first","affiliation":[{"name":"Pediatric Neurology Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Centro Clinico Nemo Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bovis","sequence":"additional","affiliation":[{"name":"Department of Health Sciences (DISSAL) University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Pera","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Centro Clinico Nemo Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome 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