Longitudinal Cohort Study of Verbatim-Reported Postural Instability Symptoms as Outcomes for Online Parkinson’s Disease Trials

Abstract

Background: The Parkinson’s Disease Patient Report of Problems (PD-PROP) captures the problems and functional impact that patients report verbatim. Online research participation and advances in language analysis have enabled longitudinal collection and classification of symptoms as trial outcomes. Objective: Analyze verbatim reports longitudinally to examine postural-instability symptoms as 1) precursors of subsequent falling and 2) newly occurring symptoms that could serve as outcome measures in randomized controlled trials. Methods: Problems reported by >25,000 PD patients in their own words were collected online in the Fox Insight observational study and classified into symptoms by natural language processing, clinical curation, and machine learning. Symptoms of gait, balance, falling, and freezing and associated reports of having fallen in the last month were analyzed over three years of longitudinal observation by a Cox regression model in a cohort of 8,287 participants. New onset of gait, balance, falling, and freezing symptoms was analyzed by Kaplan-Meier survival techniques in 4,119 participants who had not previously reported these symptoms. Results: Classified verbatim symptoms of postural instability were significant precursors of subsequent falling among participants who were older, female, and had longer PD duration. New onset of symptoms steadily increased and informed sample size estimates for clinical trials to reduce the onset of these symptoms. Conclusion: The tools to analyze symptoms reported by PD patients in their own words and capacity to enroll large numbers of research participants online support the feasibility and statistical power for conducting randomized clinical trials to detect effects of therapeutic interventions.

What Patients Say: Large-Scale Analyses of Replies to the Parkinson’s Disease Patient Report of Problems (PD-PROP)

“…Ongoing longitudinal data collection will provide detailed insight into the variable progression of symptoms at an unprecedented scale. These findings can guide clinical care, research priorities, and provide guidance for clinical trial outcomes and sample size calculation [9]. By virtue of parallel collection of demographic, lifestyle, and clinical data in Fox Insight, there now exists a rich shared resource for evaluating associations between patient reported problems and quality of life, lifestyle factors, and other experiences of the person with PD (https://www.michaeljfox.org/fox-den).…”

“…This approach proved helpful to initiate a list of topically identified symptoms for further granularization. From then on, based on 1) knowledge of the motor and non-motor symptoms of PD, 2) review of over 5300 PD-PROP responses in prior curation work [5,9], and 3) review of approximately 25 sample verbatims by each curation team member tailored to their specific area of expertise, the curation team generated a list of symptoms that were anticipated to be mentioned in the larger dataset of PD-PROP responses, and grouped them by domain (e.g., "cognition" or "autonomic"). The team of 9 curators consisted of clinicians, people with PD, and a non-clinician PD expert with extensive experience talking to people with PD in her work for a Parkinson's support and research charity.…”

Association between Subjective Cognitive Complaints and Incident Functional Impairment in Parkinson's Disease

“…The sample was comprised of persons with PD (PwP) participating in FI who had completed a PD Patient Report of Problems (PD‐PROP) assessment. PD‐PROP is a series of open‐ended questions that ask respondents to report their most bothersome problems and impact on function (up to five) 25,26 . FI participants were asked to complete the PD‐PROP by keyboard entry every 3 months.…”

“…PD-PROP is a series of open-ended questions that ask respondents to report their most bothersome problems and impact on function (up to five). 25,26 FI participants were asked to complete the PD-PROP by keyboard entry every 3 months. For baseline analyses, general inclusion criteria were 1 one or more responses to PD-PROP 2 available data on age, sex, years since PD diagnosis (YSD), cognitionrelated functional abilities (PDAQ-15 score), 20 and motorrelated function in activities of daily living (ie, Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part II score 27 ).…”

Clinical Outcome Assessments and Digital Health Technologies Supporting Clinical Trial Endpoints in Early Parkinson's Disease: Roundtable Proceedings and Roadmap for Research

“…Stebbins described some newer approaches to sensitive and patient-centered COAs, including use of emergent symptoms(Tosin et al, 2022) and asking open-ended questions, such as "What is bothering you the most right now, and how much is it bothering you?" as in the Parkinson's Disease Patient Report of Problems (PD-PROP)(Javidnia et al, 2021;Shoulson et al, 2022). Stebbins made suggestions for moving forward, including more widespread sharing of work being done to involve the patient voice, development of novel approaches such as goal attainment scales, modification of existing measures, and harmonization of methods and data.…”