(#52) Estimation of the Minimal Clinically Important Difference (MCID) and Longitudinal Change in the Tardive Dyskinesia Impact Scale (TDIS), a Validated, Tardive Dyskinesia-Specific, Patient-Reported Outcome Measure

Abstract: Tardive Dyskinesia Impact Scale (TDIS) evaluates TD symptom impact over the previous 7 days and was a KINECTÆ3, KINECTÆ4, and KINECT-PRO outcome. Objectives were to estimate minimal clinically important difference (MCID, also known as meaningful score difference) of 11-item TDIS; evaluate change in TDIS total and individual item scores longitudinally with valbenazine. Anchor- and distribution-based approaches used Patient Global Impression of Change (PGIC) (range 1-7, higher score=worsening) to estimate TDIS MCID using KINECT3/KINECT4 trial data. The anchor was a PGIC score=3 (ìminimally improvedî) at Wk6/Wk8. TDIS score changes from baseline (CFB) to Wk6 in KINECT3 and Wk8 in KINECT4 were computed from patients receiving valbenazine (40-80 mg) or placebo and had PGIC=3. To assess valbenazineís effect on TDIS, mean CFB to Wk48 in TDIS total (range=0-44; higher score=worsening) and individual item scores (range=0-4) were evaluated. For patients with PGIC=3, TDIS improvements of 3.8-3.9 points were observed by Wk6/Wk8, establishing an MCID for TDIS of 4 points. By Wk48, CFB in TDIS total score and individual items confirmed long-term valbenazine efficacy with consistent improvement in physical and socioemotional TDIS domains. When applying short-term MCID to longer-term studies, CFB to Wk48 in TDIS total score in KINECT3 (?8.4) and KINECT4 (?11.0) far exceeded MCID. A 4-point MCID was considered clinically meaningful for interpreting the change in TDIS total scores; TDIS total improvement was substantially greater than MCID through Wk48 in KINECT3/KINECT4. All TDIS items improved over 48 weeks, particularly socioemotional impacts, supporting use of TDIS to measure longitudinal change in TD burden.Short Description: We aimed to estimate the MCID (also known as meaningful score difference) of the 11-item TDIS patient-reported outcome and evaluate change in TDIS total and individual item scores longitudinally with valbenazine from KINECT3 and KINECT4 data. Using distribution- and anchor-based approaches, an MCID of 4 points was estimated for TDIS. Longitudinal improvement in TDIS total and individual items scores was observed, particularly for socioemotional impact of tardive dyskinesia.Name of Sponsoring Organization(s): Neurocrine Biosciences, Inc.