Pharm Stat. 2025 May-Jun;24(3):e70015. doi: 10.1002/pst.70015.
ABSTRACT
The term “minimal clinically important difference” (MCID), though defined as the smallest change in an outcome that is meaningful to the patient, is often used to interpret differences between treatment groups. It is in this context that the limitations of MCID are discussed, which include: the omission of the role of time in its definition for progressive diseases; the unsuitability of adopting MCID derived from open-label studies for randomized, placebo-controlled, blinded studies; the unreliability of MCID in rare disease trials; challenges in interpretation when placebo patients also achieve MCID; the failure to account for how differences in patient populations affect MCID (e.g., inclusion or exclusion of patients on prior treatment); not recognizing the connection between the true treatment effect, MCID and power; lack of consideration of differences in analysis methods (e.g., the extent of missing data and how it is handled); and the limitations of an MCID-based responder analysis. Therefore, the recommendation made is to prospectively define a customized MCID that addresses each deficit. If the deficits cannot be adequately resolved, then the recommendation is that trial results should be interpreted without reference to MCID.
PMID:40289700 | DOI:10.1002/pst.70015
