Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities

Change in AIMS total scores of items 1-7

The Abnormal Involuntary Movement Scale (AIMS) has been used for many years as the gold standard for this purpose and the amount of improvement (change in movement intensity, and reduction in AIMS scores) have been assessed clinical significance in rating improvement. A number of authors have noted the difficulty in using the AIMS in persons with IDD who cannot cooperate fully in the examination process. For this reason, some have suggested using videotaped AIMS exams as a methodology for more accurately quantifying change. Videotaping of exams pre- and post-treatment for blind rating of improvement has been a methodology utilized in a number of recent studies of valbenazine. The minimum value of the AIMS total score of items 1-7 is 0 and the maximum value is 49. Higher total AIMS scores mean worse outcomes.

CGI-C

Clinical Global Impression of Change (CGI-C), as the names indicates, denotes the clinician's impression of change between baseline and after the treatment in which -3 will be marked worsening, -2 moderate worsening, -1 mild worsening, 0 no change, +1 will be marked for mild improvement, +2 moderate improvement, and +3 marked improvement.

CaGI-C

Caregiver Global Impression of Change (CaGI-C). This is similar to the CGI-C, except that this is the impression of the participant's caregiver, -3 will be marked worsening, -2 moderate worsening, -1 mild worsening, 0 no change, +1 will be marked for mild improvement, +2 moderate improvement, and +3 marked improvement.

Change in ABC-I score

The Aberrant Behavioral Checklist, Irritability Subscale (ABC-I) is commonly used in clinical trials. It consists of 15 items, which are scored on a 4-point Likert scale of severity, ranging from "not at all a problem" to "the problem is severe in degree."

Change in W-ADL score

The Waisman Activities of Daily Living (W-ADL) Scale for adolescents and adults with developmental disabilities, is a validated scale that consists of 17 items in the final version of the W-ADL pertain to the current or expected performance of the target individual at the time when the survey was given. The target adult's performance of each activity is rated on a 3-point scale (0 = "does not do at all", 1 = "does with help", 2 = "independent"), and item scores are summed to produce an overall score. Therefore, this means that the scores can range from a minimum of 0 to a maximum value of 51. Higher total W-ADL scores mean better outcomes.

Change Simpson-Angus Scale for EPS

The Simpson-Angus Scale is a tool used to assess the severity of extrapyramidal symptoms (EPS), which are side effects of antipsychotic medications. The scale consists of ten items that assess five domains: gait, arm dropping, shoulder shaking, elbow rigidity, and wrist rigidity or fixation of position. Each item is rated on a 5-point scale of severity (0 = normal; 4 = most severe; NR = not rated). The total score ranges from 0 to 40, with higher scores indicating more severe EPS outcome.

Change in Barnes Akathisia Scale

The Barnes Akathisia Scale is a rating scale used to assess the severity of drug-induced akathisia (a syndrome of motor restlessness). It is the most widely used rating scale for akathisia. The scale consists of four items that rate the observable, restless movements that characterize the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. The scale is scored on a 4-point scale from 0-3 and is summed yielding a total score ranging from 0 to 9. The higher the score, the more severe the akathisia, i.e., the worse the outcome.

Assessment of electrocardiogram (EKG)-derived QT/QTc intervals

QTc intervals have clinical importance as a biomarker of potential drug toxicity. QTc intervals ≥ 450 ms are generally considered long, and drug-induced QTc interval prolongations ≥ 60 ms are generally considered clinically relevant.