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)
Ondo WG, Grieger F, Moran K, Kohnen R, and Roth T. 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). J Clin Sleep Med 2016; 12(1):63-70.
J Clin Sleep Med
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.
Medical Subject Headings
Adolescent; Adult; Aged; Dopamine Agonists; Double-Blind Method; Female; Humans; Internationality; Male; Middle Aged; ROC Curve; Restless Legs Syndrome; Severity of Illness Index; Surveys and Questionnaires; Tetrahydronaphthalenes; Thiophenes; Treatment Outcome; Young Adult