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Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated
Giorgia Coratti1,2, Francesca Bovis3, Maria Carmela Pera1,2
1Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy.
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.
Insights
Minimal clinically important difference (MCID) and minimal detectable change (MDC) values for the Hammersmith Functional Motor Scale Expanded (HFMSE) vary significantly between Spinal Muscular Atrophy (SMA) types II and III. Caution is advised when interpreting these values for assessing treatment response in diverse SMA populations.
Area of Science:
- Neurology
- Clinical Trials
- Biostatistics
Background:
- Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease with diverse clinical presentations.
- The Hammersmith Functional Motor Scale Expanded (HFMSE) is a key outcome measure for SMA.
- Establishing reliable MCID and MDC values is crucial for interpreting HFMSE changes in clinical trials.
Purpose of the Study:
- To calculate the minimal clinically important difference (MCID) and minimal detectable change (MDC) for the HFMSE in an untreated, international cohort of SMA patients.
- To determine if MCID and MDC values differ based on SMA type (II and III), age, and functional status.
Main Methods:
- Minimal detectable change (MDC) was calculated using distribution-based methods (standard error of measurement, effect size) in 321 SMA patients.
- Minimal clinically important difference (MCID) was assessed using anchor-based methods (ROC analysis, standard error) in 76 SMA patients, anchored to caregiver perception.
- Patients were stratified by SMA type (II and III), age, and functional status.
Main Results:
- MCID values differed between SMA type II (-2 via ROC) and type III (-4 via ROC).
- MCID values for improvement (1.5) and deterioration (-3.2) also varied when using standard error.
- Distribution-based MDC values showed variability across different age and functional subgroups within each SMA type.
Conclusions:
- A single MCID or MDC value for the HFMSE is insufficient for interpreting treatment effects in heterogeneous SMA cohorts.
- Interpretation of HFMSE changes requires consideration of individual patient characteristics, including SMA type, age, and functional status.
- These findings are critical for the accurate assessment of therapeutic responses in ongoing and future SMA clinical trials.
