Pediatric Clinical Research Office, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Academic Medical Center, H8-236, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Orphanet J Rare Dis. 2018 Sep 5;13(1):154. doi: 10.1186/s13023-018-0836-0.
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.
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.
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.
罕见病的患病率低、对疾病进程的认识不足以及表型异质性阻碍了罕见病药物的研发。如果设计和维护得当，罕见病登记处（RDR）可以通过在了解疾病进程以及为临床试验设计提供必要信息方面发挥作用来提供帮助。我们根据广泛的登记处经验描述了 RDR 的潜在应用，以及在药物开发过程中为支持临床试验设计应纳入哪些类型的信息。我们更详细地评估了两个现有的 RDR，以检查这些 RDR 在试验设计方面的完整性。
在申请监管批准之前和期间，RDR 可以通过告知样本量计算和预期疾病进程来提高临床试验设计的效率和质量。在特殊情况下，RDR 的信息已被用作单臂临床试验的历史对照，高质量的 RDR 可用于基于登记处的随机对照试验。在（有条件）药物批准的上市后阶段，特定疾病的 RDR 可能比特定产品的登记处提供更相关的信息。
RDR 可以通过多种方式非常有助于提高临床试验设计的效率和质量。为了使 RDR 的适用性和最佳使用成为可能，必须进行纵向数据收集，并且需要为重复测量而准备特定的数据收集。所开发的清单可以帮助定义要包括的适当变量。从一开始就应注意在 RDR 中纳入患者相关的结局测量指标。需要进一步研究和经验，以了解 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。
