改善路易体痴呆症临床试验格局的挑战与机遇。
Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials.
机构信息
Parkinson's Disease and Movement Disorders Program, Shirley Ryan AbilityLab and Departments of Physical Medicine and Rehabilitation and Neurology, Northwestern University Feinberg School of Medicine, 355 E. Erie Street, Chicago, IL, 60611, USA.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
出版信息
Alzheimers Res Ther. 2020 Oct 29;12(1):137. doi: 10.1186/s13195-020-00703-5.
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.
路易体痴呆症(LBD),包括路易体痴呆和帕金森病痴呆症,影响了美国超过 100 万人,给患者、护理人员和社会带来了巨大影响。LBD 的对症治疗方法包括认知、神经精神、自主神经、睡眠和运动等方面,但目前只有两种药物(胆碱酯酶抑制剂)被监管机构批准用于 LBD 痴呆症。临床试验是一个首要的研究重点,但在 LBD 临床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 临床试验领域的发展,路易体痴呆症协会成立了一个行业咨询委员会(LBDA IAC),除了卓越研究中心计划外。LBDA IAC 由来自学术医疗中心、制药行业和患者倡导基金会的多元化和协作专家组成。2019 年 6 月举行的首届 LBDA IAC 会议旨在汇集该组织以及来自监管机构的代表,共同探讨优化 LBD 临床试验格局的主题。本综述重点介绍了 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 LBD 临床评估工具和循证管理策略,以及 LBD 诊断的困难和争议。LBD 临床试验面临的挑战包括 LBD 病理学和症状学的异质性、对 LBD 认知和核心特征轨迹的理解有限、缺乏 LBD 特异性结局指标以及缺乏可能为研究设计提供信息的既定标准化生物标志物、成像或遗传标志物。研究参与的需求(例如旅行、研究持续时间和研究访问频率)也可能带来挑战并影响试验的入组、保留和结局。通过在队列和研究中协调临床评估和生物标志物、在 LBD 中开发和验证结局指标、让患者群体参与评估研究需求和优先事项以及在研究设计中纳入生物标志物和基因型分析,可以改善 LBD 临床试验的格局。