A digital patient-centered outcome tool for cervical dystonia
Sarah Pirio Richardson,
Brian D. Berman,
Janet Hieshetter,
Cynthia Comella,
David A. Peterson,
Gamze Kilic-Berkmen,
Laura Wright,
Samantha Pentecost,
Paul Reyes,
Joseph Jankovic,
Charles H. Adler,
Marina A. J. Tijssen,
Teresa J. Kimberley,
Monika Benson,
Joel S. Perlmutter,
Fares Qeadan,
H. A. Jinnah
Affiliations
Sarah Pirio Richardson
Department of Neurology, University of New Mexico Health Sciences Center and New Mexico VA Health Care System, Albuquerque, NM, United States
Brian D. Berman
Department of Neurology, Virginia Commonwealth University, Richmond, VA, United States
Janet Hieshetter
Dystonia Medical Research Foundation, Chicago, IL, United States
Cynthia Comella
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States
David A. Peterson
Computational Neurobiology Laboratory, Salk Institute for Biological Studies, and Institute for Neural Computation, University of California, San Diego (UCSD), La Jolla, CA, United States
Gamze Kilic-Berkmen
Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
Laura Wright
Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
Samantha Pentecost
Department of Neurology, University of New Mexico Health Sciences Center and New Mexico VA Health Care System, Albuquerque, NM, United States
Paul Reyes
Department of Neurology, University of New Mexico Health Sciences Center and New Mexico VA Health Care System, Albuquerque, NM, United States
Joseph Jankovic
Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, United States
Charles H. Adler
Department of Neurology, Mayo Clinic, Scottsdale, AZ, United States
Marina A. J. Tijssen
0Expertise Centre Movement Disorders, Groningen, Department of Neurology, University of Groningen, University Medical Centre Groningen (UMCG), Groningen, Netherlands
Teresa J. Kimberley
1Department of Physical Therapy, Massachusetts General Hospital (MGH) Institute of Health Professions, Boston, MA, United States
Monika Benson
2Dystonia Europe, Brussels, Belgium
Joel S. Perlmutter
Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
Fares Qeadan
3Parkinson School of Health Sciences and Public Health, Loyola University, Chicago, IL, United States
H. A. Jinnah
Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
IntroductionTo establish clinical trial readiness for dystonia, a crucial step is to develop a Patient-Centered Outcome (PCO) measure to capture therapeutic response in focal dystonia such as in cervical dystonia (CD). Botulinum neurotoxin (BoNT) is the gold standard treatment for focal dystonia and yields improvement; yet the therapy may not meet all patient expectations as there is a high rate of discontinuation. A PCO that can measure therapeutic response, including the waxing and waning benefit of BoNT, across multiple domains and is easy to use on a frequent basis in the home environment is critical.MethodsA modified iterative Delphi process based on FDA (Food and Drug Administration) guidelines was used to develop and select items to document patient symptoms and response to treatment. Potential items then were improved using patient focus groups, validated for content with specialist panels, and confirmed items based on a patient survey. Using data from 200 CD patients in the Dystonia Coalition Natural History Database, initial PCO items were identified. Utilizing Random Forests, prospective items were analyzed for their contribution to the overall severity scores on the clinical and patient-centered outcome scales. Items that were repetitive were merged. Iterative meetings with a specialist panel consisting of neurologists, physical therapists, and Patient Advocacy Group (PAG) representatives as well as virtual focus groups of CD patients were held. An online survey was conducted with over 600 CD patients participating. Finally, specialist panel members provided input for a content validity ratio (CVR) with iterations until there was good agreement as to the relevance and clarity of the items.ResultsPCO measures tailored for CD were successfully developed. The PCO consists of 16 items covering three domains (motor, disability, and psychosocial) and reflects the input of international specialist panels, more than 800 CD patients, and PAGs (patient advocacy groups) following FDA guidance. The PCO is simple enough to be used in an app-based format compatible with smartphones and tablets.ConclusionThis comprehensive CD PCO measure was developed through the combination of using robust existing patient centered data (from previous Dystonia Coalition Projects); active engagement with PAGs to provide the patient voice; and use of virtual focus groups and online surveys. This PCO will be used in a prospective study to characterize the therapeutic response to BoNT over time. This will provide peak effect size as well as capturing the “yo-yo” effect during BoNT treatment; and will prepare for a future trials.
