Disease progression strikingly differs in research and real-world Parkinson's populations

Characterization of Parkinson's disease (PD) progression using real-world evidence could guide clinical trial design and identify subpopulations. Efforts to curate research populations, the increasing availability of real-world data and recent advances in natural language processing, particularly large language models, allow for a more granular comparison of populations and the methods of data collection describing these populations than previously possible. This study includes two research populations and two real-world data derived (RWD) populations. The research populations are the Harvard Biomarkers Study (HBS, N = 935), a longitudinal biomarkers cohort study with in-person structured study visits; and Fox Insights (N = 36,660), an online self-survey-based research study of the Michael J. Fox Foundation. Real-world cohorts are the Optum Integrated Claims-electronic health records (N = 157,475), representing wide-scale linked medical and claims data and de-identified data from Mass General Brigham (MGB, N = 22,949), an academic hospital system. Structured, de-identified electronic health records data at MGB are supplemented using natural language processing with a large language model to extract measurements of PD progression. This extraction process is manually validated for accuracy. Motor and cognitive progression scores change more rapidly in MGB than HBS (median survival until H mini-mental state exam median decline 0.28 vs. 0.11, p<0.001; and clinically recognized cognitive decline, p=0.001). In the real-world populations, patients are diagnosed more than eleven years later (RWD mean of 72.2 vs. research mean of 60.4, p<0.001). After diagnosis, in real-world cohorts, treatment with PD medications is initiated 2.3 years later on average (95% CI: 2.1-2.4; p<0.001). This study provides a detailed characterization of Parkinson's progression in diverse populations. It delineates systemic divergences in the patient populations enrolled in research settings vs. patients in the real world. These divergences are likely due to a combination of selection bias and real population differences, but exact attribution of the causes is challenging using existing data. This study emphasizes a need to utilize multiple data sources and to diligently consider potential biases when planning, choosing data sources, and performing downstream tasks and analyses.