Rare disease registries: potential applications towards impact on development of new drug treatments
Rare disease registries: potential applications towards impact on development of new drug treatments
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DOI：
10.1186/s13023-018-0836-0
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发表时间：
2018-09-05
影响因子：
3.7
通讯作者：
van der Lee, Johanna H.
中科院分区：
文献类型：
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作者：
Jansen-van der Weide, Marijke C.;Gaasterland, Charlotte M. W.;van der Lee, Johanna H.
背景：低患病率，缺乏对疾病过程的了解，以及表型异质性阻碍了罕见病药物的开发。如果设计和维护得当，罕见病登记（RDRs）可以在了解疾病过程中发挥作用，并为临床试验设计提供必要的信息。我们描述了RDR的潜在应用，以及在药物开发过程中应纳入何种类型的信息以支持临床试验的设计，基于广泛的注册经验。我们评估了两个现有的RDRs在更详细地检查这些RDRs的完整性为trial design.Results：之前和期间申请监管批准RDR可以提高效率和质量的临床试验设计，通知样本量计算和预期的疾病过程。在特殊情况下，来自RDR的信息被用作单臂临床试验的历史对照，高质量的RDR可用于基于注册的随机对照试验。在上市后阶段的（有条件的）药物批准的疾病特异性RDR可能提供更多的相关信息比产品特异性registry.Conclusions：RDR可以是非常有帮助的，以提高效率和质量的临床试验设计在几个方面。为了使RDR的适用性和最佳使用，纵向数据收集是必不可少的，并且需要为重复测量做好准备的具体数据收集。所制定的清单有助于确定要包括的适当变量。应注意从一开始就将患者相关结局指标纳入RDR。需要更多的研究和经验，以了解将RDR信息与临床试验数据相结合的可能性和局限性，以最大限度地为罕见病的监管决策提供相关证据。
Background: Low prevalence, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of drugs for rare diseases. Rare disease registries (RDRs) can be helpful by playing a role in understanding the course of the disease, and providing information necessary for clinical trial design, if designed and maintained properly. We describe the potential applications of a RDR and what type of information should be incorporated to support the design of clinical trials in the process of drug development, based on a broad inventory of registry experience. We evaluated two existing RDRs in more detail to check the completeness of these RDRs for trial design.Results: Before and during the application for regulatory approval a RDR can improve the efficiency and quality in clinical trial design by informing the sample size calculation and expected disease course. In exceptional circumstances information from RDRs has been used as historical controls for a one-armed clinical trial, and high quality RDRs may be used for registry-based randomized controlled trials. In the post marketing phase of (conditional) drug approval a disease-specific RDR is likely to provide more relevant information than a product-specific registry.Conclusions: A RDR can be very helpful to improve the efficiency and quality of clinical trial design in several ways. To enable the applicability and optimal use of a RDR longitudinal data collection is indispensable, and specific data collection, prepared for repeated measurement, is needed. The developed checklist can help to define the appropriate variables to include. Attention should be paid to the inclusion of patient-relevant outcome measures in the RDR from the start. More research and experience is needed on the possibilities and limitations of combining RDR information with clinical trial data to maximize the availability of relevant evidence for regulatory decisions in rare diseases.