Invited Review: Minimal Clinically Important Differences in Measuring Treatment Effects in CIDP History, Current Use, Limitations, and Prospects-Article

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This invited review in Muscle & Nerve (2025) by Rajabally et al. addresses the concept and application of minimal clinically important differences (MCIDs) in chronic inflammatory demyelinating polyneuropathy (CIDP), focusing on treatment effect measures. MCID is defined as the smallest change in an outcome measure perceived as beneficial by patients, important for interpreting meaningful treatment responses beyond statistically significant results.<br /><br />CIDP, a treatable immune-mediated neuropathy causing motor and sensory disability, relies on various scales to evaluate treatment outcomes. The MCID concept has grown in importance to assess clinical relevance in trials and practice. MCIDs can be derived via anchor-based methods (using patient perspectives through health-related quality of life [HR-QoL] or patient global impression scales) or distribution-based methods (based on statistical thresholds such as standard error or standard deviation). Each approach has strengths and limitations; anchor-based methods capture patient relevance but may suffer bias or inadequate anchors, while distribution methods are statistically grounded but may lack direct clinical meaning.<br /><br />The review summarizes literature deriving MCIDs for CIDP outcome measures including the Inflammatory Neuropathy Cause and Treatment (INCAT) scale, Overall Neuropathy Limitation Scale (ONLS), Rasch-built Overall Disability Scale (I-RODS), Medical Research Council sum score (MRCSS), grip strength, and walking tests. The INCAT, ONLS, and I-RODS disability scales have relatively consistent and validated MCIDs (e.g., INCAT 1 point), supporting their suitability for clinical and research use. However, discrepancies exist especially for strength measures (grip strength, MRCSS) and timed walking tests where MCID thresholds vary widely and may reflect measurement variability rather than meaningful change.<br /><br />The review also highlights variability in MCID derived from disease severity and CIDP subtype heterogeneity, questioning uniform application of single cut-offs. Recent trials mostly use the INCAT scale MCID for defining improvement or relapse, while I-RODS and grip strength have more inconsistent application. Some analyses suggest available MCIDs lie within natural measurement variability, challenging their discriminative validity. Still, the authors argue the MCID concept remains valuable but calls for better harmonization of derivation methods and further research to optimize outcome measures.<br /><br />Importantly, the paper notes limited integration of HR-QoL measures, which are theoretically well-suited for MCID use since they relate directly to patient-perceived benefit. Expanded use of disease-specific HR-QoL scales could enhance assessment of meaningful clinical benefit in CIDP.<br /><br />In conclusion, despite limitations and unresolved issues, MCIDs for disability scales like INCAT, ONLS, and I-RODS are currently the most reliable measures for assessing treatment impact in CIDP. Strength and sensory measures show less reliability, and sensory and electrophysiological scales have little established MCID relevance. The authors emphasize continued refinement of MCID definitions, including in relation to HR-QoL metrics, to better guide clinical trials and practice in CIDP management.

Keywords

Minimal Clinically Important Differences

MCID

Chronic Inflammatory Demyelinating Polyneuropathy

cidp

Treatment Effect Measures

INCAT Scale

ONLS Scale

I-RODS Scale

Health-Related Quality of Life

Anchor-based and Distribution-based Methods