Weighing Different Scales: Unified Dyskinesia Rating Scale Comes Out on Top
Researchers funded by The Michael J. Fox Foundation (MJFF) have identified the best clinical scale for measuring patient response to therapies to treat dyskinesia, the debilitating, uncontrollable movements that are often a side effect of Parkinson's disease (PD) drugs.
The $1-million study, led by co-coordinating principal investigators Chris Goetz, MD, and Glenn Stebbins, PhD, of Rush University Medical Center, was launched in 2010 at eight sites across the United States, Canada and Europe. It has now demonstrated that the Unified Dyskinesia Rating Scale (UDysRS) most sensitively tracks treatment effect.
Establishing UDysRS as a validated tool for use in dyskinesia clinical trials could have important implications: Researchers should be able to better design conclusive clinical trials to verify that a dyskinesia drug is or isn't working.
The study also quantified the therapeutic effect of amantadine, a PD drug commonly used off-label to alleviate dyskinesia, as a baseline by which to measure future potential treatments.
MJFF spoke with Stebbins and Scientific Advisory Board member David Weiner, MD, to gauge what the study results could mean for the development of new dyskinesia therapies, a major unmet need for those living with Parkinson's today.
MJFF: What is a clinical rating scale?
GS: Basically, clinical rating scales measure the severity of an individual's symptoms. They can be based on a physician's rating of a patient, information gathered from interviewing a patient and/or caregiver or they can be based on the self-report of a patient and/or caregiver. Regardless of the method of data collection, clinical rating scales are important tools for researchers trying to measure whether or not a drug works.
It's important to note that rating scales are based on the best judgment/opinion of the clinician or the self-reported data and recollection of the patient. This is different from an objective test (like a blood test or a brain scan) that doesn't rely on opinion, recollection or other subjective factors. It is also important to note that no rating scale is perfect and all scales are associated with a little bit of error in measurement.
MJFF: Tell us more about how doctors measure patients' dyskinesia.
GS: Dyskinesia severity is difficult to measure because it is so variable day to day and even over the course of a single day. A person's level of dyskinesia can be directly related to many factors such as when an individual takes their medication, how much medication they take or their emotional state when the rating scale is completed. The variable presentation of dyskinesia makes measuring it very difficult.
Compounding this issue, to date, is that several different scales measuring dyskinesia have been used by clinicians. Yet, there hasn't been any real evidence as to which the clinical rating scales were most useful for measuring whether drugs were working or not. This has made it hard to compare results from patient to patient and from study to study -- complicating the ability to draw clear conclusions.
Historically the scales that researchers have used to measure dyskinesia are based on three types of reporting: physician-driven patient interviews about the scope of an individual's dyskinesia (including questions about the on/off cycle and how disabling patients feel their dyskinesia can be), patient self-report on these types of questions, and in-the-clinic observations. Most rating scales use only one of these approaches to assess dyskinesia, and may miss important information that the other methods might capture.
UDysRS was designed to include all three of these methods of data collection. It is derived from some of the best parts of the other rating scales that were studied in this trial; it's a scale that unifies these different sources of data into one scale. When we developed the UDyrRS, we had reason to hope that it would prove the best measure for testing patient response to dyskinesia drugs.
MJFF: How did this study take form?
DW: Physicians currently prescribe a drug called amantadine, initially developed as an anti-viral drug, to treat dyskinesia. While it certainly works for some, it's not a great drug -- there are problems with side effects and often the effect wears off after a short time. People with Parkinson's are still in desperate need of a really good anti-dyskinetic drug.
But researchers figured out that amantadine could play an important role in the rating scale study: The trial would to compare amantadine to placebo, and then use various dyskinesia scales to see which did the best job of detecting any clinical benefit of amantadine.
By identifying the scale that did this best, researchers could use the data on amantadine as a baseline marker to test the effect of any future drug. According to the results, it looks like Goetz and Stebbins' team have accomplished this. And more than that, they've found that the Unified Dyskinesia Rating Scale is the best scale for most sensitively tracking a treatment's effect.
MJFF: Will UDysRS be a critical tool for drug developers?
GS: Because we have been able to show that the scale is sensitive to dyskinesia treatment with amantadine, researchers should now be able to use this information to better design conclusive clinical trials of new anti-dyskinetic drugs.
DW: A senior executive at a pharmaceutical company is much more likely to green-light a clinical trial of a potential dyskinesia drug now that we have a solid technique to measure therapeutic effect. Ultimately, it takes this kind of investment to move drug candidates to the clinic and pharmacy shelves. For this reason, UDysRS could have major implications for people with Parkinson's battling dyskinesia.
MJFF: What is the current state of dyskinesia drug development?
DW: Promising. It is an active area of drug development, with multiple compounds currently at the phase 2 testing stage. UDysRS may help to secure investment for further clinical studies into drug candidates to treat dyskinesia.
GS: The fact that there is currently no therapy approved by the FDA to treat dyskinesia represents a major unmet need for people with Parkinson's. But there has been a big push over the past few years in both academia and the pharmaceutical industry to develop drugs to treat this side effect. We're hopeful that the UDysRS will be a useful tool to help translate budding research into approved treatments.