Post Hoc Analysis of Data from Two Clinical Trials Evaluating the Minimal Clinically Important Change in International Restless Legs Syndrome Sum Score in Patients with Restless Legs Syndrome (Willis-Ekbom Disease)

Abstract

Study Objectives: Determine the minimal clinically important change (MCIC), a measure determining the minimum change in scale score perceived as clinically beneficial, for the international restless legs syndrome (IRLS) and restless legs syndrome 6-item questionnaire (RLS-6) in patients with moderate to severe restless legs syndrome (RLS/Willis-Ekbom disease) treated with the rotigotine transdermal system. Methods: This post hoc analysis analyzed data from two 6-mo randomized, double-blind, placebo-controlled studies (SP790 [NCT00136045]; SP792 [NCT00135993]) individually and as a pooled analysis in rotigotine-treated patients, with baseline and end of maintenance IRLS and Clinical Global Impressions of change (CGI Item 2) scores available for analysis. An anchor-based approach and receiver operating characteristic (ROC) curves were used to determine the MCIC for the IRLS and RLS-6. We specifically compared "much improved vs minimally improved," "much improved/very much improved vs minimally improved or worse," and "minimally improved or better vs no change or worse" on the CGI-2 using the full analysis set (data as observed). Results: The MCIC IRLS cut-off scores for SP790 and SP792 were similar. Using the pooled SP790+SP792 analysis, the MCIC total IRLS cut-off score (sensitivity, specificity) for "much improved vs minimally improved" was −9 (0.69, 0.66), for "much improved/very much improved vs minimally improved or worse" was −11 (0.81, 0.84), and for "minimally improved or better vs no change or worse" was −9 (0.79, 0.88). MCIC ROC cut-offs were also calculated for each RLS-6 item. Conclusions: In patients with RLS, the MCIC values derived in the current analysis provide a basis for defining meaningful clinical improvement based on changes in the IRLS and RLS-6 following treatment with rotigotine.

Improvement of restless leg syndrome in maintenance hemodialysis patients with limb ischemic preconditioning: a single-center randomized controlled clinical trial

“…According to a study conducted by Ondo et al., the reduction in the International Restless Legs Scale (IRLS) score of 5 points can be defined as the minimal clinically important change [ 16 , 17 ]. Given this threshold, a decrease of ≥ 5 points in the IRLS score of patients after intervention was defined as clinical improvement.…”

Placebo and nocebo responses in other movement disorders besides Parkinson's disease: How much do we know?

“…17 Interestingly, the reported magnitude of a placebo response exceeded the proposed threshold for a minimal clinically important difference (MCID) in the IRLS (i.e., 5.6 points). 18,19 A pooled nocebo response defined as the proportion of patients experiencing adverse events in the placebo arm was reported to be 45.4% (95% CI: 40.5, 50.3).…”