Detecting a clinically meaningful change in tic severity in Tourette syndrome: A comparison of three methods

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). Method: Subjects (N = 232; 69.4% male; ages 9-69 years) 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-TI'S 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. Theodds 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% Cl = [1.65, 4.99]). Conclusion: 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. (C) 2013 Elsevier Inc. All rights reserved.