title: Detecting a clinically meaningful change in tic severity in Tourette syndrome: a comparison of three methods.
abstract: OBJECTIVE
  To compare three statistical strategies for classifying positive treatment response based on a dimensional measure (Yale Global Tic Severity Scale [YGTSS]) and a categorical measure (Clinical Global Impression-Improvement [CGI-I] scale).
  
  
  METHODS
  Subjects (N=232; 69.4% male; ages 9-69years) with Tourette syndrome or chronic tic disorder participated in one of two 10-week, randomized controlled trials comparing behavioral treatment to supportive therapy. The YGTSS and CGI-I were rated by clinicians blind to treatment assignment. We examined the percent reduction in the YGTSS-Total Tic Score (TTS) against Much Improved or Very Much Improved on the CGI-I, computed a signal detection analysis (SDA) and built a mixture model to classify dimensional response based on the change in the YGTSS-TTS.
  
  
  RESULTS
  A 25% decrease on the YGTSS-TTS predicted positive response on the CGI-I during the trial. The SDA showed that a 25% reduction in the YGTSS-TTS provided optimal sensitivity (87%) and specificity (84%) for predicting positive response. Using a mixture model without consideration of the CGI-I, the dimensional response was defined by 23% (or greater) reduction on the YGTSS-TTS. The odds ratio (OR) of positive response (OR=5.68, 95% CI=[2.99, 10.78]) on the CGI-I for behavioral intervention was greater than the dimensional response (OR=2.86, 95% CI=[1.65, 4.99]).
  
  
  CONCLUSIONS
  A 25% reduction on the YGTSS-TTS is highly predictive of positive response by all three analytic methods. For trained raters, however, tic severity alone does not drive the classification of positive response. Clinicaltrials.gov identifiers: NCT00218777; NCT00231985.
authors.affiliation: School of Nursing, Yale University, New Haven, CT, United States.
authors.forename: Sangchoon
authors.initials: S
authors.lastname: Jeon
authors.forename: John T
authors.initials: JT
authors.lastname: Walkup
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Woods
authors.forename: Alan
authors.initials: A
authors.lastname: Peterson
authors.forename: John
authors.initials: J
authors.lastname: Piacentini
authors.forename: Sabine
authors.initials: S
authors.lastname: Wilhelm
authors.forename: Lily
authors.initials: L
authors.lastname: Katsovich
authors.forename: Joseph F
authors.initials: JF
authors.lastname: McGuire
authors.forename: James
authors.initials: J
authors.lastname: Dziura
authors.forename: Lawrence
authors.initials: L
authors.lastname: Scahill
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001521:Behavior Therapy / Q000379:methods; D002648:Child; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020323:Tics / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy; D005879:Tourette Syndrome / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D016896:Treatment Outcome; D055815:Young Adult
keywords: Clinical Global Impression; Cognitive behavioral intervention; Mixture model; Signal detection analysis; Tourette syndrome; Yale Global Tic Severity Scale