Does Baseline Disease Severity Impact the Meaningful Score Difference of Clinical Outcome Assessments? Results From Studies in Two Itching-Related Skin Conditions

OBJECTIVES: Evidence to support the interpretability of COA-based endpoints in clinical trials is essential to evaluate treatment benefit. The FDA and EMA agencies recommend methods to do this, one of which quantifies the size difference between two COA scores that are meaningful for patients “meaningful score difference” (MSD)¹. We explored if reports of MSD of a sleep disturbance numerical rating scale [SD NRS] differed according to baseline SD NRS severity scores among patients with itching-related skin conditions associated sleep disturbances (SD) using quantitative and qualitative approaches.

METHODS: Multiple data sets were used: 1) Quantitative data (n=114) from a Phase 2b trial in in atopic dermatitis (AD); 2) Qualitative real-world study (n=28) in AD; and 3) Qualitative real-world study data (n=19) in prurigo nodularis (PN). For each data set, baseline patient scores were dichotomized (SD NRS ≥7, SD NRS <7) and meaningful improvement ranges explored.

RESULTS: Anchor-based analyses identified the most frequent improvement in the SD NRS score was 6- to 7-points for the AD sample with SD NRS < 7 baseline score (25.9%) and 7- to 8-points for those with SD NRS ≥ 7 baseline score (34.5%).

Qualitative analyses identified that a greater proportion of the AD sample in the SD NRS ≥7 severity group expected an improvement of ≥ 4 points compared to SD NRS <7 severity group (38% vs. 13%).

Qualitative analyses identified that a greater proportion of the PN SD NRS ≥ 7 group expected improvement of ≥ 4 points compared to the SD NRS < 7 group (44% vs. 10%).

CONCLUSIONS: Among the datasets examined, baseline SD severity score influenced the MSD in SD NRS among patients with AD and PN. Those with a lower baseline severity score reported a lower MSD or actually experienced a lower MSD following trial treatment.