Through recent collaborative efforts, the FDA and EMA are hoping to encourage multi-arm, multi-company clinical trials for pediatric rare diseases. This white paper examines how registries can provide a valuable foundation for these types of trials by fostering long-term, collaborative relationships between rare disease stakeholders and improving our understanding of diseases and treatment outcomes.
介绍In July 2017, the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) published a joint proposal on multi-arm, multi-company clinical trials, which would use a single control arm to compare multiple medicines.1 The proposal – focusing on Gaucher disease, but intended as a general roadmap for pediatric rare diseases – would allow for economies of scale as multiple sponsors could share the responsibility and cost of identifying and recruiting patients. This guidance does not eliminate any of the existing requirements for rare disease drug development; however, the FDA and EMA may exercise flexibility in determining the kind and quantity of data required to meet the statutory standard.
该方法可以通过增加安全性和有效性数据的数量和质量来更好地确定相对风险效益；随着监管机构激励赞助商考虑这些试验，并导致了更平滑的监管途径。尽管拟议方法存在重大障碍，但在罕见疾病研究中多公司合作的过程中，开发注册表的协作努力可以看作是积极的一步。
注册表的承诺
稀有疾病登记处通常具有以下目标：
- 为了联系患者，他们的护理人员和临床医生
- To better understand the natural history and outcomes of the rare disease
- 支持对疾病的遗传，分子和生理基础的研究
- 建立一个评估潜在疗法和医疗设备的患者基础。
Data from registries can significantly benefit early-stage drug development, and potentially serve as a starting point for multi-arm, multi-company clinical trials. Registries can help address many challenges inherent in rare disease trials, allowing for a more complete understanding of the disease course and variability; guiding the development of endpoint measures, patient reported outcomes (PROs) and biomarkers; facilitating feasibility assessments for future trials; providing a source of patients for clinical trials; and gathering longer term safety and efficacy data after registration trials are completed.
稀有疾病登记还可以通过提供有关疾病自然史的信息，为样本量计算提供信息，用作销售后监测的历史对照组，或检查全球不同治疗方案的现实生活结果数据，来改善临床试验设计。
SUCCESSFUL ONGOING INITIATIVES
Disease-focused, not-for-profit foundations and patient advocacy groups have a proven track record of operating registries in the public interest and can serve as models for future collaborations. Sponsors work in parallel to access specific data sets relevant to their R&D assets, helping to inform clinical development without disclosing commercially sensitive information. This may form the basis for future collaboration between sponsors on multi-company, multi-arm trials.