Critical Path Institute, Tucson, AZ, USA.
Janssen Research & Development, Raritan, NJ, USA.
Diabetologia. 2023 Mar;66(3):415-424. doi: 10.1007/s00125-022-05751-0. Epub 2022 Jul 22.
The development of medical products that can delay or prevent progression to stage 3 type 1 diabetes faces many challenges. Of note, optimising patient selection for type 1 diabetes prevention clinical trials is hindered by significant patient heterogeneity and a lack of characterisation of the time-varying probability of progression to stage 3 type 1 diabetes in individuals positive for two or more islet autoantibodies. To meet these needs, the Critical Path Institute's Type 1 Diabetes Consortium was launched in 2017 as a pre-competitive public-private partnership between stakeholders from the pharmaceutical industry, patient advocacy groups, philanthropic organisations, clinical researchers, the National Institutes of Health and the Food and Drug Administration. The Type 1 Diabetes Consortium acquired and aggregated data from three longitudinal observational studies, Environmental Determinants of Diabetes in the Young (TEDDY), Diabetes Autoimmunity Study in the Young (DAISY) and TrialNet Pathway to Prevention (TN01), and used analysis subsets of these data to support the model-based qualification of islet autoantibodies as enrichment biomarkers for patient selection in type 1 diabetes prevention trials, including registration studies. The Type 1 Diabetes Consortium has now received a qualification opinion from the European Medicines Agency for the use of these biomarkers, a major success for the field of type 1 diabetes. This endorsement will improve product developers' ability to design clinical trials of agents intended to prevent or delay type 1 diabetes that are reduced in size and/or length, while being adequately powered.
开发能够延缓或阻止 1 型糖尿病进展至 3 期的医学产品面临诸多挑战。值得注意的是,由于患者存在显著异质性,以及缺乏对两例及以上胰岛自身抗体阳性者进展至 3 期 1 型糖尿病的时间变化概率的特征描述,因此优化 1 型糖尿病预防临床试验的患者选择受到阻碍。为满足这些需求,美国关键路径研究所的 1 型糖尿病联盟于 2017 年成立,这是一个制药行业、患者权益团体、慈善组织、临床研究人员、美国国立卫生研究院和美国食品药品监督管理局之间的非竞争型公私合作伙伴关系。1 型糖尿病联盟从三个纵向观察性研究中获取和汇总数据,即儿童期糖尿病的环境决定因素(TEDDY)、儿童期糖尿病自身免疫研究(DAISY)和试验网预防途径(TN01),并使用这些数据的分析子集来支持将胰岛自身抗体作为 1 型糖尿病预防试验(包括注册研究)中患者选择的富集生物标志物进行基于模型的资格认定,这是 1 型糖尿病领域的重大成功。目前,1 型糖尿病联盟已收到欧洲药品管理局关于使用这些生物标志物的资格认定意见,这将提高产品开发人员设计旨在预防或延缓 1 型糖尿病的药物临床试验的能力,这些临床试验规模更小、/或时间更短,但具有足够的效力。