Wanner Adam, Groft Stephen C, Teagarden J Russell, Krischer Jeffrey, Davis Barry R, Coffey Christopher S, Hickam David H, Teckman Jeffrey, Nelson David R, McCaleb Michael L, Loomba Rohit, Strange Charlie, Sandhaus Robert A, Brantly Mark, Edelman Jonathan M, Farrugia Albert
Division of Pulmonary and Critical Care Medicine, University of Miami and Alpha-1 Foundation, Miami, Florida.
Chronic Obstr Pulm Dis. 2015 Apr 28;2(2):177-190. doi: 10.15326/jcopdf.2.2.2015.0132.
Clinical research in rare diseases, including alpha-1 antitrypsin deficiency (AATD), faces challenges not shared by common disease research. These challenges may include the limited number of patient volunteers available for research, lack of natural history studies on which to base many clinical trial interventions, an urgency for the development of drug therapies given the often poor prognosis of rare diseases and uncertainties about appropriate biomarkers and clinical outcomes critical to clinical trial design. To address these challenges and initiate formal discussions among key stakeholders-patients, researchers, industry, federal regulators-the Alpha-1 Foundation hosted the conference February 3-4, 2014 in Bethesda, Maryland. Discussions at the conference led to the conclusions that 1) adaptive designs should be considered for rare disease clinical trials yet more dialogue and study is needed to make these designs feasible for smaller trials and to address current limitations; 2) natural history studies, including the identification of appropriate biomarkers are critically needed and precompetitive collaborations may offer a means of creating these costly studies; and 3) patient registries and databases within the rare disease community need to be more publicly available and integrated, particularly for AATD. This report summarizes the discussions leading to these conclusions.
包括α-1抗胰蛋白酶缺乏症（AATD）在内的罕见病临床研究面临着常见疾病研究所没有的挑战。这些挑战可能包括可供研究的患者志愿者数量有限、缺乏作为许多临床试验干预基础的自然史研究、鉴于罕见病通常预后不良而产生的药物治疗开发紧迫性，以及对于临床试验设计至关重要的合适生物标志物和临床结局的不确定性。为应对这些挑战并在关键利益相关者（患者、研究人员、行业、联邦监管机构）之间展开正式讨论，α-1基金会于2014年2月3日至4日在马里兰州贝塞斯达举办了此次会议。会议讨论得出以下结论：1）对于罕见病临床试验应考虑采用适应性设计，但需要更多的对话和研究，以使这些设计适用于规模较小的试验并解决当前的局限性；2）迫切需要进行自然史研究，包括确定合适的生物标志物，而竞争性前合作可能提供开展这些成本高昂的研究的一种方式；3）罕见病群体中的患者登记处和数据库需要更公开可用且相互整合，尤其是对于AATD。本报告总结了得出这些结论的讨论情况。
