title: 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: OBJECTIVE
  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.
authors.affiliation: University of Texas Health Science Center-Houston, Houston, TX.
authors.forename: William G
authors.initials: WG
authors.lastname: Ondo
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Grieger
authors.affiliation: UCB Pharma, Smyrna, GA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Moran
authors.affiliation: Formerly of RPS Research Germany, Nurnberg, Germany (deceased).
authors.forename: Ralf
authors.initials: R
authors.lastname: Kohnen
authors.affiliation: Henry Ford Hospital, Detroit, MI.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018491:Dopamine Agonists / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012148:Restless Legs Syndrome / Q000175:diagnosis* / Q000188:drug therapy*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires / Q000592:standards*; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: IRLS; RLS-6; clinical study; dopamine agonist; minimal clinically important change; restless legs syndrome; rotigotine; sleep disturbance