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).

Method: 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]).

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.

Keywords: Clinical Global Impression; Cognitive behavioral intervention; Mixture model; Signal detection analysis; Tourette syndrome; Yale Global Tic Severity Scale.

© 2013.

Figures

Figure 1. Mean YGTSS-TTS against CGI-I ratings and the estimated probability of CGI-I score based on the percent reduction on the YGTSS-TTS at Week 10 for the entire sample (N=232)

Figure on the left indicates the mean of YGTSS-TTS at baseline (open circles) and Week 10 (black circles). The figure on the right shows the probability of CGI-I score at Week 10 derived from generalized logits model based on the percent reduction on YGTSS-TTS from baseline. For example, a 25% reduction in the YGTSS-TTS has about a 30% chance of being rated Much Improved; a 50% reduction in the YGTSS-TTS has 60% chance of being rated Much Improved. Positive response was defined as Much Improved or Very Much Improved. Thus, the probability of positive response is equal to the probability of Much Improved (CGI=2) plus the probability of Very Much Improved (CGI=1). the probability of CGI=2 decreases as the improvement in the YGTSS-TTS exceeds 50%, but the probability of CGI=1 incrementally increases with greater than 50% improvement in YGTSS. Therefore, the summed probabilities of the CGI=2 and CGI=1 increases as the decline in the YGTSS-TTS exceeds 50%.

Figure 2. Treatment response based on (CGI-I) and the Response Model at Week 10

The low YGTSS-TTS at baseline come from subjects (31.5%) with only motor of vocal tics.