{"doi":"10.1038/s41531-024-00667-5","title":"Disease progression strikingly differs in research and real-world Parkinson’s populations","abstract":"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 advances in natural language processing, particularly large language models, allow for a more granular comparison of 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 a manually validated natural language processing with a large language model to extract measurements of PD progression. Motor and cognitive progression scores change more rapidly in MGB than HBS (median survival until H&Y 3: 5.6 years vs. >10, p < 0.001; mini-mental state exam median decline 0.28 vs. 0.11, p < 0.001; and clinically recognized cognitive decline, p = 0.001). In 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 has initiated an average of 2.3 years later (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. 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.","journal":"npj Parkinson s Disease","year":2024,"id":429721,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":285361,"name":"Francesca Frau","orcid":"0009-0001-4568-0316","position":1,"is_corresponding":false},{"id":1232825,"name":"Sylvie Bozzi","orcid":null,"position":2,"is_corresponding":false},{"id":1232400,"name":"Karen J. Chandross","orcid":"0000-0002-1346-2162","position":3,"is_corresponding":false},{"id":656538,"name":"Michel Peterschmitt","orcid":"0000-0003-4686-0412","position":4,"is_corresponding":false},{"id":67695,"name":"Caroline Cohen","orcid":null,"position":5,"is_corresponding":false},{"id":1232826,"name":"Catherine Coulovrat","orcid":null,"position":6,"is_corresponding":false},{"id":563414,"name":"Dinesh Kumar","orcid":"0000-0002-6143-2507","position":7,"is_corresponding":false},{"id":1232827,"name":"Mark J Kruger","orcid":null,"position":8,"is_corresponding":false},{"id":68237,"name":"Scott L. Lipnick","orcid":"0000-0002-4271-746X","position":9,"is_corresponding":false},{"id":1232828,"name":"Lane Fitzsimmons","orcid":null,"position":10,"is_corresponding":false},{"id":3527,"name":"Isaac S. Kohane","orcid":"0000-0003-2192-5160","position":11,"is_corresponding":false},{"id":271547,"name":"Clemens R. Scherzer","orcid":"0000-0002-0567-9193","position":12,"is_corresponding":false},{"id":7875,"name":"Brett K. Beaulieu‐Jones","orcid":"0000-0002-6700-1468","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:59:11.328802Z","pmid":"38480700","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}