A consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson’s Disease

Background A comprehensive, widely-accepted, patient-centered conceptual model of Parkinson’s disease (PD) is needed to improve therapeutic development and guide selection of relevant endpoints. Objectives To develop an evidence-based conceptual model of early PD, defined as <3 years since clinical diagnosis, that meets the needs of all relevant stakeholders, including people with PD, researchers, clinicians, industry, and regulators. Method A multi-stakeholder taskforce and patient advisory panel oversaw the systematic review and meta-synthesis of qualitative and quantitative studies using JBI Mixed Methods Review criteria and GRADE-CERQual standards for assessment of evidence quality, with iterative taskforce and advisory meetings to develop the model. Results More than 340 symptoms and impacts were identified from 38 unique study samples. These were grouped into 10 symptom domains (Movement, Cognitive, Psychiatric, Sleep, Sensory, Speech, Digestive, Urinary, Sexual, Autonomic) and two impact domains (Physical functioning, Psychosocial functioning). Synthesis of findings tables (SOFT) indicate that a wide range of motor and non-motor symptoms are prevalent and bothersome in early PD, with strongest evidence for tremor, dexterity, gait, stiffness, and slow movements, as well as cognitive changes (e.g., word finding issues), mood and sleep alterations, urinary dysfunction, constipation, pain, and fatigue. These commonly affected mobility, self-concept, coping, effort of living, interpersonal interactions and important activities, with evidence of many understudied impacts. Conclusion This consensus-based conceptual model of early PD provides the most comprehensive catalogue of meaningful symptoms and functional impacts to date. The model and SOFT offer evidence-based tools for identification of concepts of interest to define endpoints for clinical trials.