ALD Healthy Planet Project

ALD 健康星球计划

• 批准号: 10851183
• 负责人: FLORIAN S EICHLER
• 金额: $ 51.2万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10851183
• 关键词: Adrenal gland hypofunction; Adrenoleukodystrophy; Adrenomyeloneuropathy; Brain imaging; Cerebrum; Cessation of life; Child Health; Childhood; Clinical; Clinical Research; Clinical Trials Network; Code; Collaborations; Complex; Data; Data Collection; Disease; District of Columbia; Early Diagnosis; Electronic Health Record; Endocrinology; Ensure; Environment; Funding; Future; Generations; Guidelines; Health Services Accessibility; Healthcare Systems; Infrastructure; Institutional Review Boards; Intervention; Life; Manuals; Measures; Medical Care Team; Monitor; Natural History; Neonatal Screening; Outcome; Pediatric Hospitals; Peroxisomal Disorders; Phase; Phenotype; Philadelphia; Planets; Population; Protocols documentation; Rare Diseases; Recommendation; Resources; Risk; Safety; Site; System; Testing; Work; boys; dashboard; data pipeline; disability; early screening; evidence base; family burden; follow-up; health equity; improved; leukodystrophy; non-compliance; programs; screening guidelines; screening panel; screening program; standard of care; success; tool; Adrenal gland hypofunction; Adrenoleukodystrophy; Adrenomyeloneuropathy; Brain imaging; Cerebrum; Cessation of life; Child Health; Childhood; Clinical; Clinical Research; Clinical Trials Network; Code; Collaborations; Complex; Data; Data Collection; Disease; District of Columbia; Early Diagnosis; Electronic Health Record; Endocrinology; Ensure; Environment; Funding; Future; Generations; Guidelines; Health Services Accessibility; Healthcare Systems; Infrastructure; Institutional Review Boards; Intervention; Life; Manuals; Measures; Medical Care Team; Monitor; Natural History; Neonatal Screening; Outcome; Pediatric Hospitals; Peroxisomal Disorders; Phase; Phenotype; Philadelphia; Planets; Population; Protocols documentation; Rare Diseases; Recommendation; Resources; Risk; Safety; Site; System; Testing; Work; boys; dashboard; data pipeline; disability; early screening; evidence base; family burden; follow-up; health equity; improved; leukodystrophy; non-compliance; programs; screening guidelines; screening panel; screening program; standard of care; success; tool

X-linked adrenoleukodystrophy (ALD) is a fatal peroxisomal disorder characterized by three distinct phenotypes: cerebral ALD (cALD), adrenomyeloneuropathy (AMN), and Addison’s only (adrenal insufficiency or AI). In 2016, ALD was added to the Recommended Uniform Screening Panel (RUSP), and it has been implemented to date in 36 states and Washington DC. ALD poses a unique challenge in newborn screening follow up. While treatments for cALD and AI are effective and life-saving, they are only implemented once there is evidence of disease involvement. In the case of cALD, there is a narrow window for intervention that is limited to the earliest phase of disease. This has created a major challenge—boys identified via newborn screening must be intensely followed throughout childhood by serial brain imaging and by endocrinologic testing. There is an urgent unmet need for a rigorous automated system to track compliance with recommended follow up testing. We will leverage our existing Rare Diseases Clinical Research Network (RDCRN) Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN; U54TR002823) to deploy this system and measure its efficacy. In Aim 1, the CHOP Healthy Planets EPIC programming team, who originally developed the ALD monitoring dashboard in collaboration with the CHOP Leukodystrophy Center of Excellence will work with local EPIC programmers at Children’s Hospital of Atlanta, Stanford Children’s Health, and Kennedy Krieger Institute, sharing code and facilitating the adaptation of the CHOP system to local EPIC environments. The expected outcome is a functional ALD monitoring dashboard and an open-access manual on how this approach can be more broadly implemented to additional sites. In Aim 2, we will establish the data collection pipeline to establish data-driven monitoring guidelines. Leveraging the existing electronic health records program within the GLIA- CTN, we will establish the data pipeline for centralization of ALD-monitoring. We will collect and curate the data across the GLIA-CTN implementation sites. The expected outcome is a curated data pipeline and generation of pilot data to understand if existing monitoring guidelines are appropriate for a post newborn screening ALD population. The expected outcome is generation of data collection tool necessary to establish evidence-based post newborn screening guidelines. While the ALD field has been transformed by early detection and ground-breaking therapies, there is an urgent, unmet need for system to monitor compliance with long term monitoring needs. This pipeline can support presymptomatic natural history studies and establish standard of care monitoring guidelines that are data-driven. The proposed work is both clinically necessary and will help to support future hypothesis-driven work. This strategy has the potential to improve health equity, ensuring that decreased access to care does not equal decreased safety and monitoring. Additionally, the general approach can be adapted to other newborn screening programs and rare disorders with complex longitudinal monitoring needs.

X连锁的肾上腺素肌营养不良症（ALD）是一种致命的过氧化物体疾病，其特征是三个不同的 表型：大脑ALD（CALD），肾上腺瘤病（AMN）和Addison（肾上腺功能不全或 人工智能）。 2016年，ALD被添加到建议的统一筛选面板（RUSP）中，并且已经 迄今为止在36个州和华盛顿特区实施。 ALD在新生儿筛查中提出了一个独特的挑战 跟进。虽然CALD和AI的治疗方法有效且挽救生命，但仅在那里实施它们 是疾病参与的证据。对于CALD，有一个狭窄的干预窗口有限 到最早的疾病阶段。这造成了一个重大挑战 - 通过新生儿筛查确定的男孩 必须通过串行大脑成像和内分泌测试来积极遵循整个童年时期。 严格的自动化系统需要紧急未满足以跟踪推荐的符合性 后续测试。我们将利用现有的稀有疾病临床研究网络（RDCRN）全球 白细胞营养不良计划临床试验网络（Glia-CTN; U54TR002823）部署此系统和测量 它的有效性。在AIM 1中，Chop Healthy Planets Epic编程团队最初开发了ALD 与CHOP LEUKODYTROPHY CENTRARES合作监视仪表板将与当地合作 亚特兰大儿童医院，斯坦福儿童健康和肯尼迪·克里格研究所的Epic程序员， 共享代码并支持将CHOP系统改编为本地Epic环境。预期 结果是功能性的ALD监视仪表板和一本关于该方法如何的开放访问手册 更广泛地实施到其他站点。在AIM 2中，我们将建立数据收集管道以建立 数据驱动的监视指南。利用Glia中的现有电子健康记录计划 CTN，我们将建立用于ALD-Monitoring集中化的数据管道。我们将收集和策划数据 跨神经胶质CTN实施站点。预期的结果是精心策划的数据管道和生成 试点数据以了解现有的监视指南是否适合新生儿筛查ALD 人口。预期的结果是建立基于证据的数据收集工具的生成 新生儿筛查指南。 尽管ALD领域已通过早期检测和突破性疗法进行了转化，但有一个 紧急，未满足的系统需要监视长期监控需求的遵守情况。该管道可以支持 预抑制性自然史研究并建立数据驱动的护理监测指南。 拟议的工作在临床上是必要的，并且将有助于支持未来的假设驱动的工作。这 策略有可能提高健康平等的潜力，确保减少护理的机会不相等 安全性和监控降低。此外，可以将一般方法适应其他新生儿筛查 具有复杂纵向监测需求的程序和罕见疾病。