Beaulieu-Jones Brett K, Frau Francesca, Bozzi Sylvie, Chandross Karen J, Peterschmitt M Judith, Cohen Caroline, Coulovrat Catherine, Kumar Dinesh, Kruger Mark J, Lipnick Scott L, Fitzsimmons Lane, Kohane Isaac S, Scherzer Clemens R
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
APDA Center for Advanced Parkinson Research of Harvard Medical School and Brigham and Women's Hospital, Boston, MA, 02115, USA.
NPJ Parkinsons Dis. 2024 Mar 13;10(1):58. doi: 10.1038/s41531-024-00667-5.
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.
利用真实世界证据对帕金森病（PD）进展进行特征描述，可为临床试验设计提供指导并识别亚组人群。精心策划研究人群的努力、真实世界数据可用性的增加以及自然语言处理（尤其是大语言模型）的进展，使得对人群进行比以往更细致的比较成为可能。本研究包括两个研究人群和两个源自真实世界数据（RWD）的人群。研究人群为哈佛生物标志物研究（HBS，N = 935），这是一项纵向生物标志物队列研究，有面对面的结构化研究访视；以及福克斯洞察（Fox Insights，N = 36,660），这是迈克尔·J·福克斯基金会基于在线自我调查的研究。真实世界队列是Optum综合理赔 - 电子健康记录（N = 157,475），代表大规模关联的医疗和理赔数据，以及来自学术医院系统马萨诸塞州综合医院布莱根分院（MGB，N = 22,949）的去标识化数据。MGB的结构化、去标识化电子健康记录数据通过使用经人工验证的带有大语言模型的自然语言处理进行补充，以提取PD进展的测量值。MGB中运动和认知进展评分的变化比HBS更快（直至H&Y 3期的中位生存期：5.6年对>10年，p < 0.001；简易精神状态检查中位下降0.28对0.11，p < 0.001；以及临床认可的认知下降，p = 0.001）。在真实世界人群中，患者被诊断的时间要晚超过11年（RWD均值为72.2对研究均值为60.4，p < 0.001）。诊断后，在真实世界队列中，开始使用PD药物治疗的平均时间要晚2.3年（95%置信区间：[2.1 - 2.4]；p < 0.001）。本研究详细描述了不同人群中帕金森病的进展情况。它描绘了研究环境中纳入的患者人群与真实世界患者之间的系统性差异。这些差异可能是由于选择偏倚和真实人群差异共同导致的，但确切归因具有挑战性。本研究强调在规划、选择数据源以及执行下游任务和分析时，需要利用多个数据源并认真考虑潜在偏倚。
