Disease progression strikingly differs in research and real-world Parkinson's populations
© 2024. The Author(s)..
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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
NPJ Parkinson's disease - 10(2024), 1 vom: 13. März, Seite 58 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Beaulieu-Jones, Brett K [VerfasserIn] |
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Date Revised 25.03.2024 published: Electronic UpdateOf: medRxiv. 2024 Feb 18;:. - PMID 38405736 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1038/s41531-024-00667-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369704002 |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Bozzi, Sylvie |e verfasserin |4 aut | |
| 700 | 1 | |a Chandross, Karen J |e verfasserin |4 aut | |
| 700 | 1 | |a Peterschmitt, M Judith |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Coulovrat, Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Dinesh |e verfasserin |4 aut | |
| 700 | 1 | |a Kruger, Mark J |e verfasserin |4 aut | |
| 700 | 1 | |a Lipnick, Scott L |e verfasserin |4 aut | |
| 700 | 1 | |a Fitzsimmons, Lane |e verfasserin |4 aut | |
| 700 | 1 | |a Kohane, Isaac S |e verfasserin |4 aut | |
| 700 | 1 | |a Scherzer, Clemens R |e verfasserin |4 aut | |
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