Karaa Amel, MacMullen Laura E, Campbell John C, Christodoulou John, Cohen Bruce H, Klopstock Thomas, Koga Yasutoshi, Lamperti Costanza, van Maanen Rob, McFarland Robert, Parikh Sumit, Rahman Shamima, Scaglia Fernando, Sherman Alexander V, Yeske Philip, Falk Marni J
Department of Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Adv Genet (Hoboken). 2022 Mar;3(1). doi: 10.1002/ggn2.202100047. Epub 2021 Dec 19.
Primary mitochondrial diseases (PMD) are genetic disorders with extensive clinical and molecular heterogeneity where therapeutic development efforts have faced multiple challenges. Clinical trial design, outcome measure selection, lack of reliable biomarkers, and deficiencies in long-term natural history data sets remain substantial challenges in the increasingly active PMD therapeutic development space. Developing "FAIR" (findable, accessible, interoperable, reusable) data standards to make data sharable and building a more transparent community data sharing paradigm to access clinical research metadata are the first steps to address these challenges. This collaborative community effort describes the current landscape of PMD clinical research data resources available for sharing, obstacles, and opportunities, including ways to incentivize and encourage data sharing among diverse stakeholders. This work highlights the importance of, and challenges to, developing a unified system that enables clinical research structured data sharing and supports harmonized data deposition standards across clinical consortia and research groups. The goal of these efforts is to improve the efficiency and effectiveness of drug development and improve understanding of the natural history of PMD. This initiative aims to maximize the benefit for PMD patients, research, industry, and other stakeholders while acknowledging challenges related to differing needs and international policies on data privacy, security, management, and oversight.
原发性线粒体疾病(PMD)是一类具有广泛临床和分子异质性的遗传疾病,其治疗开发工作面临诸多挑战。在日益活跃的PMD治疗开发领域,临床试验设计、结局指标选择、缺乏可靠的生物标志物以及长期自然史数据集的不足仍是重大挑战。制定“FAIR”(可查找、可访问、可互操作、可重用)数据标准以使数据可共享,并建立更透明的社区数据共享范式以获取临床研究元数据,是应对这些挑战的第一步。这项社区合作工作描述了可用于共享的PMD临床研究数据资源的现状、障碍和机遇,包括激励和鼓励不同利益相关者之间数据共享的方式。这项工作强调了开发一个统一系统的重要性和挑战,该系统能够实现临床研究结构化数据共享,并支持跨临床联盟和研究组的统一数据存储标准。这些努力的目标是提高药物开发的效率和效果,并增进对PMD自然史的了解。该倡议旨在使PMD患者、研究、行业和其他利益相关者的利益最大化,同时认识到与数据隐私、安全、管理和监督方面不同需求及国际政策相关的挑战。