The Tardive Dyskinesia Impact Scale complements the Abnormal Involuntary Movement Scale by combining clinician-rated and patient-reported perspectives.
Tardive dyskinesia (TD) is a debilitating movement disorder characterized by abnormal involuntary movements that significantly impact physical, cognitive, and psychosocial well-being. According to a recent study, the Abnormal Involuntary Movement Scale (AIMS), a clinician-rated outcome, is the gold standard for assessing treatment efficacy in TD clinical trials. However, a recent study led by Morgan Bron, PharmD, director, HEOR, Neurocrine Biosciences, contends that AIMS lacks insights into the patient perspective and can be cumbersome to administer in clinical settings. Addressing these limitations, researchers developed the Tardive Dyskinesia Impact Scale (TDIS) as a patient-reported outcome to provide a more comprehensive understanding of the impact of TD.
To evaluate the TDIS, Dr. Bron’s study drew upon data from qualitative studies and phase 3 trials involving a VMAT2 inhibitor for TD treatment. Qualitative research involved concept elicitation and cognitive debriefing interviews with TD patients and their caregivers that gauged how the TDIS effectively captured key domains of TD impact. Quantitative analyses focused on assessing the psychometric properties of the TDIS, including construct validity, known groups, predictive validity, and responsiveness to change.
The results indicated that the TDIS successfully captured the essential impacts of TD, as reported by patients and caregivers. Furthermore, the quantitative analyses revealed two underlying domains of the TDIS—physical and socioemotional—demonstrating a robust factor structure with a Comparative Fit Index exceeding 0.9.
Notably, the TDIS exhibited unique content compared with the AIMS, establishing its distinct contribution to TD assessment (the correlation between AIMS and TDIS ranged from 0.2 to 0.28). Moreover, the TDIS demonstrated responsiveness to changes in treatment over the 48-week duration of the phase 3 trials.
Overall, the TDIS emerged as a valuable tool for assessing the impact of TD. The study team found it offered ease of administration in both clinical and home settings, and its longitudinal application enabled monitoring changes in TD burden over time. Importantly, according to the study, the TDIS complements the AIMS, providing a more holistic evaluation of TD by combining clinician-rated and patient-reported perspectives.
Physician’s Weekly (PW) spoke with Dr. Bron to better understand the benefits of TDIS and how physicians can leverage TDIS in their practice to monitor and understand the progression or improvement of TD in their patients.
PW: Can you elaborate on how the TDIS was developed and what specific patient-reported outcomes it measures?
Morgan Bron. PharmD: The TDIS was developed here at Neurocrine. Bob Farber and Chris O’Brien were the developers before I came on board and developed in a manner aligned with FDA guidance. The TDIS is patient-reported, which means the patient fills out a scale or survey that asks about certain aspects of their lives. We call them domains, and those ask the patient about the impact TD may have on various metrics, for example, mouth movements, throat swallowing, dexterity, ability to do everyday movements, mobility, standing or walking pain, and lastly, socialization and emotional aspects of their lives. In our research, having a patient report outcomes allows the patient to tell us how they feel and how their symptoms affect their daily activities. As I said, the questionnaire was designed to capture what’s relevant for TD patients, so what’s relevant to the disease, not necessarily just what is happening to the patient, but specifically what TD symptoms have affected their lives.
How does the TDIS differ from AIMS in assessing the impact of TD?
AIMS is a 12-item clinician-rated scale used to assess the severity of movement disorders. You can follow that over time, and you have seven items on the scale to assess movement in different body regions. The physician or HCP will rate each item from zero to four—zero is normal, no movements, and four is severe. The sum of those seven questions or body region areas of evaluation is the total score. Scores on the AIMS range from zero to 28. AIMS is helpful in understanding the severity of TD over time in terms of movement, but the TDIS gives you a measure that enables you to examine the physical, social, and emotional aspects of the disease from the patient’s perspective. I like that in terms of giving you a more complete picture. AIMS gives you movement, and TDIS gives you impact from a patient perspective. You get two sides of the story.
How can physicians leverage the TDIS in their practice?
AIMS is important to look at movement over time, but it’s also important to assess the severity of TD and the impact of what those movements can have on your ability to function. In our research, we’ve used the TDIS to determine your disease burden and then to see what treatment could do for that disease burden over time. We’ve used this scale in two of our clinical trials—KINECT3 and KINECT4. Those trials have different time points. We have primary endpoints at certain weeks but have followed these patients over longer periods. I think it gives you not only movement over time but also the impact of TD over time.
Those could help the physician understand how a treatment strategy is working? Is this appropriate? Could I do something different? What is the course of this condition? And is whatever I’m using for treatment or strategies working?
What benefits could the TDIS offer to provide a more holistic understanding of TD?
What’s interesting is that the TDIS is rather short right now. We’re committed to educating clinicians regarding screening practices, including learnings of our clinical trials and the use of TDIS in our research. If you think about clinical practice and if you think about the skills that you use, something that’s shorter is probably easier to implement. I think that the importance of having a tool that you can use easily and the importance of having that tool ask the right questions targeted to that specific disease is important. It’s interesting that you think, yes, there’s movement, but people living with TD also feel a lot of other things. The disease has a negative impact on them, not only physically, but it’s also social and emotional. There are feelings of being judged for movements. Do I have to worry about what people think of me? Does that lead to isolation and stigma? And it doesn’t have to be necessarily large or severe movements; even mild uncontrollable movements can have an emotional and social impact on a patient’s life.
Do you have any final thoughts?
We are still doing work and research with the TDIS. We’ll be publishing more as time goes on. We continue to refine our analysis, trying to understand the clinical importance of some of these changes for our scoring. We’re also trying to understand if there are certain domains or aspects of the TDIS that drive the scores for improvement. So, stay tuned for more data as we explore the properties of the scale. I think that’s exciting from a research standpoint, and I think it just gives patients and providers more information on what you can capture from this tool.
