The FOG-COA Protocol: Validation of Freezing of Gait Clinical Outcomes Assessments in Parkinson's Disease

Abstract

The development and evaluation of novel treatment options for freezing of gait (FOG) in Parkinson's disease have been limited by an ambiguous definition and lack of standardized clinical outcome assessments (COAs) that 1) reliably assess FOG severity, 2) are responsive to change, and 3) capture patient-relevant impact. To address these gaps, working groups from the International Consortium on FOG (ICFOG) developed a clinician-rated outcome—the Giladi Protocol for assessing FOG severity (GP-FOG), and a patient-reported outcome—the FOG Quality of Life questionnaire (FOG-QOL). The FOG-COA project will evaluate the conceptual framework and psychometric properties of these COAs to determine their fit-for-purpose in clinical trials. A total of 105 freezers and 35 non-freezers from seven international centers will complete the GP-FOG in the dopaminergic OFF and ON states during two separate visits (7–14 days apart). FOG annotations from video recordings will be used to assess criterion validity. OFF and ON GP-FOG scores from two trained raters at Visit 1, as well as within-rater scores across visits, will examine reliability. Responsiveness will be evaluated by comparing effect sizes between OFF and ON GP-FOG scores. Patient meaningfulness will be assessed through the association between patient-perceived FOG severity and GP-FOG scores. Participants will complete the FOG-QOL at each visit to assess test–retest reliability and validity against the NFOGQ and PDQ-8. A subset of freezers will undergo cognitive interviews to identify relevant daily life FOG impacts and evaluate FOG-QOL meaningfulness. Collectively, this work will advance standardized, sensitive, and meaningful FOG-COAs, supporting regulatory-grade endpoints and the development of a multi-dimensional outcome framework.