A 3-point median score change may be considered an MCID for a robust response.
The persistent involuntary movement disorder tardive dyskinesia (TD) has been associated with extended exposure to dopamine-receptor blocking agents (DRBA). Treatment of this disorder recently advanced with the approval of valbenazine (Ingrezza) by US Food and Drug Administration (FDA) as the first and only medication indicated for the treatment of TD in adults.
In well-controlled clinical trials of valbenazine, investigators showed its efficacy by rating TD severity with the Abnormal Involuntary Movement Scale (AIMS) consensus score of 2 central video raters blinded to treatment group and visit sequence. In clinical research, the minimal clinically important difference (MCID) is the magnitude of change in such a score in subjects who received a defined level of benefit from a study agent. However, researchers had not determined an MCID for AIMS total score in TD patients until recently.
A team led by Mark Stacy, MD, (pictured) professor of neurology and vice dean for clinical research at Duke University School of Medicine in Durham, North Carolina, determined such an MCID by analyzing pooled data from the KINECT studies, three 6-week, randomized, double-blind, placebo-controlled trials of once-daily valbenazine in adults with TD. Stacy detailed the results of their analysis during a poster presentation at the 21st International Congress of Parkinson’s Disease and Movement Disorders in Vancouver, BC.
The team based their MCID analysis on data from 373 patients in the pooled intention-to-treat (ITT) KINECT population, defined as participants from each KINECT study who took at least 1 dose of study drug and had at least 1 AIMS assessment after baseline. In this population, baseline characteristics were similar across treatment groups. Mean patient age was roughly 56 years in each group, and most patients were men.
KINECT included patients with a diagnosis of schizophrenia, schizoaffective disorder, or mood disorder who were psychiatrically stable. KINECT patients also had DRBA-induced TD for at least 3 months before screening and moderate or severe TD determined by a blinded, external reviewer based on an AIMS video recorded during patient screening.
In addition, KINECT patients had no active, clinically significant, and unstable medical condition within a month of screening. Moreover, patients were excluded from KINECT if they had a comorbid movement disorder that was more prominent than TD or a substantial risk of active suicidal thoughts or behavior or of acting violently.
However, patients could take stable doses of concomitant medications including antipsychotic agents to treat psychiatric disorders throughout the KINECT studies.
To evaluate TD improvement, the KINECT investigators used mean change from baseline to Week 6 in AIMS total score and mean score at Week 6 on the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) scale. Therefore, Stacy and team used 2 definitions of CGI-TD response as anchors for their MCID analyses. These included a robust response, defined as a CGI-TD score of 1 (very much improved) or 2 (much improved) at Week 6, or a minimal response, defined as a CGI-TD score of 3 (minimally improved) or better at Week 6.
Based on these 2 anchors, the team determined 2 potential MCIDs: AIMS median score change from baseline to Week 6 in those with a robust CGI-TD response, and those with a minimal CGI-TD response. The team did both MCID analyses regardless of treatment.
Based on their analysis, the team determined that the median change from baseline in AIMS total score was −3.0 in those with a robust response and −2.0 in those with a minimal or better one. They considered these 2- and 3-point median score changes to be potential MCIDs for the AIMS total score in adults with TD.
Furthermore, they noted that researchers who do TD trials by using methods similar to those used in KINECT may utilize these median score changes as MCIDs. However, they that recommended additional analyses be done to broaden the generalizability of these MCIDs.