Stoeckel Luke E, Fazio Elena M, Hardy Kristina K, Kidwiler Nicole, McLinden Kristina A, Williams Benfeard
National Institute on Aging Rockville USA.
National Institute of Neurological Disorders and Stroke Bethesda Maryland USA.
Alzheimers Dement (N Y). 2025 Feb 19;11(1):e70058. doi: 10.1002/trc2.70058. eCollection 2025 Jan-Mar.
On March 12-14, 2024, the National Institute on Aging (NIA) together with the National Institute of Neurological Disorders and Stroke (NINDS) led a workshop exploring clinically meaningful changes in the context of Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) clinical trials (https://www.nia.nih.gov/research/dbsr/workshops/clinically-meaningful-outcomes-ad-adrd-trials). The goals were to identify research gaps, opportunities, and tools to advance patient-centered, equitable assessment of clinically meaningful change focused on biomarker status, cognition, and everyday function. The workshop fostered robust, multidisciplinary discussion between lived experience experts, advocates, researchers, clinicians, funders, payers, and regulators. The workshop addressed the criteria used to assess whether an intervention has had a clinically meaningful impact, including consideration of both benefit and harm. Here, we report on (1) criteria to consider for development, testing, and selection of clinically meaningful outcomes in AD/ADRD clinical trials; (2) methods to validate and customize clinically meaningful outcomes that are fit-for-purpose; and (3) practices that will ensure that clinically meaningful outcomes are applicable to diverse populations.
: Inclusive AD/ADRD clinical trials incorporate assessments that reflect what matters most to those impacted by these diseases, including patient- and caregiver-reported outcome measures. : There is a need for culturally sensitive and equitable assessments to better serve diverse populations in AD/ADRD research. : We present a framework for defining and evaluating clinically meaningful outcomes in AD/ADRD trials, tailored to diverse stages of disease progression. : We draw on insights from a multidisciplinary workshop, fostering collaboration among researchers, clinicians, and lived experience experts to advance the field.
2024年3月12日至14日，美国国立衰老研究所（NIA）与国立神经疾病和中风研究所（NINDS）共同主办了一次研讨会，探讨在阿尔茨海默病及阿尔茨海默病相关痴呆症（AD/ADRD）临床试验背景下具有临床意义的变化（https://www.nia.nih.gov/research/dbsr/workshops/clinically-meaningful-outcomes-ad-adrd-trials）。目标是确定研究差距、机会和工具，以推进以患者为中心、公平的对具有临床意义变化的评估，重点关注生物标志物状态、认知和日常功能。该研讨会促进了有生活经验的专家、倡导者、研究人员、临床医生、资助者、支付方和监管者之间进行有力的多学科讨论。研讨会讨论了用于评估干预措施是否产生了具有临床意义影响的标准，包括对益处和危害的考量。在此，我们报告：（1）在AD/ADRD临床试验中开发、测试和选择具有临床意义结果时应考虑的标准；（2）验证和定制适用的具有临床意义结果的方法；（3）确保具有临床意义结果适用于不同人群的做法。
包容性的AD/ADRD临床试验纳入了反映这些疾病对受影响者最重要事项的评估，包括患者和护理人员报告的结局指标。
需要进行文化敏感和公平的评估，以更好地服务于AD/ADRD研究中的不同人群。
我们提出了一个在AD/ADRD试验中定义和评估具有临床意义结果的框架，该框架针对疾病进展的不同阶段进行了调整。
我们借鉴了多学科研讨会的见解，促进研究人员、临床医生和有生活经验的专家之间合作，以推动该领域发展。
