A Decision Support Tool for the Discontinuation of Disease Modifying Therapies in Multiple Sclerosis

停止多发性硬化症疾病修饰疗法的决策支持工具

• 批准号: 10739870
• 负责人: Marisa McGinley
• 金额: $ 13.29万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739870
• 关键词: Decision; Support; Tool; Discontinuation; Disease

Project summary The treatment of multiple sclerosis (MS) has been transformed with the introduction of disease-modifying therapies (DMTs), but these medications DMTs have known risks and are a significant financial burden for many people with MS and for the healthcare system as a whole. Nationally, prescription drugs account for 10- 15% of total healthcare spending, but, for people with MS, prescription drugs account for more than two-thirds of their total healthcare expenditures. The benefits of DMTs are clear early in the disease course, where they have been shown to prevent relapses and the accumulation of lesions in the central nervous system. Later in the disease course, the combination of immunosenscence and a shift from widespread neuroinflammation to neurodegeneration results in diminished biological benefits of DMTs and a shift in the risk/benefit ratio in people with MS. The most common risks associated with DMTs are infections, which have been reported to be as high as 19.7 per 1000 person-years. Studies have also shown that infectious complications tend to increase with both age and increased years of DMT exposure. For these biological, financial, and risk reasons discontinuation of DMT in certain individuals should be considered. There is a growing body of observational research supporting the notion that there is a safe time to discontinue DMTs with a low risk of recurrent disease activity. These studies all suggest that older patients who have been on a DMT for several years without active disease (no relapses, no new MRI lesions) have a low likelihood of recurrent disease activity after discontinuing DMT. Despite the growing evidence to support DMT discontinuation there is a lack of consensus from neurological societies and there is no standardized approach to this clinical decision. This study seeks to develop and validation a machine learning based point of care decision support tool to standardize the approach to MS DMT discontinuation. This study will develop the machine learning algorithm in a large retrospective clinical cohort and externally validate the tool in the “Discontinuation of disease modifying therapies in multiple sclerosis” (DISCOMS; NCT 03073603) randomized, controlled, single-blinded, clinical trial dataset during the R21 phase. In the R33 phase the validated point of care tool will be implemented through a pragmatic randomized clinical trial to assess the adoption and impact on clinical outcomes over 24 months. The overarching goal of this proposal is to create a decision support tool that will provide a standardized approach to DMT discontinuation resulting in a reduction in risk exposure and financial burden to people with MS.

项目摘要 多发性硬化症（MS）的治疗已经随着疾病修饰的引入而改变。 治疗（DMT），但这些药物DMT具有已知的风险，并且是一个重大的经济负担， 许多MS患者和整个医疗保健系统。在全国范围内，处方药占10- 医疗保健总支出的15%，但是，对于MS患者，处方药占三分之二以上 占他们医疗保健总支出的DMT的益处在病程早期就很明显， 已显示可预防复发和中枢神经系统损伤的累积。晚些 疾病的过程，免疫敏感性的组合和从广泛的神经炎症到 神经退行性变导致DMT的生物学益处减少， 与DMT相关的最常见风险是感染，据报道， 高达19.7/1000人年。研究还表明，感染性并发症往往会增加 随着年龄的增长和DMT暴露年限的增加。出于这些生物学、金融和风险的原因 应考虑在某些个体中停止DMT。有越来越多的观察机构 研究支持这样的观点，即有一个安全的时间停止DMT，复发风险较低 疾病活动。这些研究都表明，接受DMT治疗数年的老年患者 无活动性疾病（无复发，无新的MRI病变）的患者复发疾病活动的可能性较低 停止DMT治疗后尽管越来越多的证据支持DMT停药，但缺乏 神经学学会达成共识，并且对于这种临床决策没有标准化的方法。这 研究旨在开发和验证基于机器学习的护理决策支持工具， 规范MS DMT停药的方法。本研究将开发机器学习算法 在大型回顾性临床队列中，并在“疾病终止”中外部验证该工具 多发性硬化的改良疗法”（DISCOMS; NCT 03073603），随机、对照、单盲， R21阶段的临床试验数据集。在R33阶段，经确认的床旁工具将 通过一项务实的随机临床试验实施，以评估采用情况和对临床的影响。 24个月的成果。本提案的总体目标是创建一个决策支持工具， 为DMT停药提供标准化方法，从而降低风险暴露和财务风险。 给MS患者带来负担。