Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials.
Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials.
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DOI：
10.1186/s13195-020-00703-5
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发表时间：
2020-10-29
期刊：
影响因子：
--
通讯作者：
Graham T
中科院分区：
文献类型：
--
作者：
Goldman JG;Forsberg LK;Boeve BF;Armstrong MJ;Irwin DJ;Ferman TJ;Galasko D;Galvin JE;Kaufer D;Leverenz J;Lippa CF;Marder K;Abler V;Biglan K;Irizarry M;Keller B;Munsie L;Nakagawa M;Taylor A;Graham T
路易体痴呆症（Lewy body dementia，LBD），包括路易体痴呆症和帕金森病痴呆症，在美国影响超过一百万人，对患者、护理人员和社会产生重大影响。LBD的症状治疗，包括认知、神经精神、自主神经、睡眠和运动特征，目前仅两种药物（胆碱酯酶抑制剂）被监管机构批准用于LBD痴呆。临床试验是研究的重中之重，但在LBD试验的开发和实施中存在许多挑战。为了解决这些问题并推进LBD的临床试验领域，路易体痴呆症协会除了其卓越研究中心计划外，还成立了行业咨询理事会（LBDA IAC）。LBDA IAC由来自学术医疗中心，制药行业和患者倡导基金会的专家组成的多元化和协作小组。首届LBDA IAC会议于2019年6月举行，旨在将该小组与监管机构的代表沿着，以解决优化LBD临床试验环境的主题。本文综述了LBDA IAC的形成，LBD临床试验的现状，以及该领域在试验设计，研究人群，诊断标准和生物标志物利用方面的挑战和机遇。目前的差距包括缺乏标准化的临床评估工具和循证管理策略，以及在诊断LBD的困难和争议。LBD临床试验的挑战包括LBD病理学和病理学的异质性，对LBD认知和核心特征的轨迹的理解有限，缺乏LBD特异性结局指标，以及缺乏可为研究设计提供信息的已建立标准化生物学，成像或遗传生物标志物。参与研究的要求（例如，旅行、持续时间和研究访视频率）也可能带来挑战并影响试验入组、保留和结局。有机会改善LBD临床试验的景观，通过协调临床评估和生物标志物跨队列和研究研究，开发和验证LBD的结局指标，让患者社区参与评估研究需求和优先事项，并将生物标志物和基因型分析纳入研究设计。
Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson’s disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body Dementia Association formed an Industry Advisory Council (LBDA IAC), in addition to its Research Center of Excellence program. The LBDA IAC comprises a diverse and collaborative group of experts from academic medical centers, pharmaceutical industries, and the patient advocacy foundation. The inaugural LBDA IAC meeting, held in June 2019, aimed to bring together this group, along with representatives from regulatory agencies, to address the topic of optimizing the landscape of LBD clinical trials. This review highlights the formation of the LBDA IAC, current state of LBD clinical trials, and challenges and opportunities in the field regarding trial design, study populations, diagnostic criteria, and biomarker utilization. Current gaps include a lack of standardized clinical assessment tools and evidence-based management strategies for LBD as well as difficulty and controversy in diagnosing LBD. Challenges in LBD clinical trials include the heterogeneity of LBD pathology and symptomatology, limited understanding of the trajectory of LBD cognitive and core features, absence of LBD-specific outcome measures, and lack of established standardized biologic, imaging, or genetic biomarkers that may inform study design. Demands of study participation (e.g., travel, duration, and frequency of study visits) may also pose challenges and impact trial enrollment, retention, and outcomes. There are opportunities to improve the landscape of LBD clinical trials by harmonizing clinical assessments and biomarkers across cohorts and research studies, developing and validating outcome measures in LBD, engaging the patient community to assess research needs and priorities, and incorporating biomarker and genotype profiling in study design.
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影响因子：
48
作者：
Irwin, David;Grossman, Murray;Weintraub, Daniel;Hurtig, Howard I.;Duda, John E.;Xie, Sharon X.;Lee, Edward B.;Van Deerlin, Vivianna M.;Lopez, Oscar L.;Kofler, Julia K.;Nelson, Peter T.;Jicha, Gregory A.;Woltjer, Randy;Quinn, Joseph F.;Kaye, Jeffery;Leverenz, James B.;Tsuang, Debby;Longfellow, Katelan;Yearout, Dora;Kukull, Walter;Keene, C. Dirk;Montine, Thomas J.;Zabetian, Cyrus P.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
DOI：
10.1016/j.trci.2018.04.008
发表时间：
2018
期刊：
Alzheimer's & dementia (New York, N. Y.)
影响因子：
--
作者：
Cummings J;Reiber C;Kumar P
通讯作者：
Kumar P
影响因子：
8.6
作者：
Espay, Alberto J.;Hausdorff, Jeffrey M.;Maetzler, Walter
通讯作者：
Maetzler, Walter
影响因子：
1.5
作者：
Frank, Samuel;Berk, Sarah;Simon, David K.
通讯作者：
Simon, David K.
影响因子：
2.4
作者：
Lapid, Maria I.;Kuntz, Karen M.;Boeve, Bradley F.
通讯作者：
Boeve, Bradley F.