Regulatory strategies for rare diseases under current global regulatory statutes: a discussion with stakeholders
Regulatory strategies for rare diseases under current global regulatory statutes: a discussion with stakeholders
复制标题
DOI：
10.1186/s13023-019-1017-5
复制
发表时间：
2019-02-08
影响因子：
3.7
通讯作者：
Kessler, Vivian
中科院分区：
文献类型：
--
作者：
Mulberg, Andrew E.;Bucci-Rechtweg, Christina;Kessler, Vivian
罕见或孤儿疾病通常是遗传性的，对儿童的影响非常大。这些疾病中有许多没有治疗方法，无法治愈，并对患者及其家人产生毁灭性的影响。罕见病药物审批的监管标准必须确保患者获得安全有效的治疗。然而，监管机构在将这些标准应用于罕见病药物开发方面表现出了灵活性，因为这些标准阻碍了高效和有效的传统临床试验，包括患者人数少，对疾病病理和进展的了解有限，疾病表现的变异性，缺乏既定的终点。为了在当前全球监管法规下采取措施改善罕见病临床开发策略，Amicus Therapeutics，Inc.和BioNJ召开了为期一天的会议，包括来自食品和药物管理局（FDA），生物制药行业和非营利机构的代表。会议重点关注儿童和成人患者中的孤儿疾病，旨在通过开放式合作确定克服监管障碍的潜在策略。会议期间，确定了几种策略，以最大限度地减少罕见疾病患者人数少的限制，包括使用自然史生成比较，模拟，并确定入选/排除标准和适当的终点。讨论了临床试验设计的新方法，以尽量减少患者对安慰剂的暴露，并减少提供实质性证据所需的患者和临床试验数量。还讨论了新的统计分析方法，以解决患者人数少的固有挑战。确定了未满足的迫切需求领域，包括需要开发保护患者身份的登记系统，在申办者和监管机构之间建立密切的合作和沟通以应对方法和统计挑战，在多个申办者内部的竞争前机会中进行合作，并与学术界和特定疾病的患者倡导团体合作以实现最佳数据共享，并制定从源数据外推到目标儿科人群的统一指南。最终，这些创新将有助于解决罕见病药物开发中的许多监管挑战，并鼓励为罕见病患者提供新的治疗方法。
Rare or orphan diseases often are inherited and overwhelmingly affect children. Many of these diseases have no treatments, are incurable, and have a devastating impact on patients and their families. Regulatory standards for drug approval for rare diseases must ensure that patients receive safe and efficacious treatments. However, regulatory bodies have shown flexibility in applying these standards to drug development in rare diseases, given the unique challenges that hinder efficient and effective traditional clinical trials, including low patient numbers, limited understanding of disease pathology and progression, variability in disease presentation, and a lack of established endpoints.To take steps toward improving rare disease clinical development strategies under current global regulatory statutes, Amicus Therapeutics, Inc. and BioNJ convened a 1-day meeting that included representatives from the Food and Drug Administration (FDA), biopharmaceutical industry, and not-for-profit agencies. The meeting focused on orphan diseases in pediatric and adult patients and was intended to identify potential strategies to overcome regulatory hurdles through open collaboration.During this meeting, several strategies were identified to minimize the limitations associated with low patient numbers in rare diseases, including the use of natural history to generate historical control data in comparisons, simulations, and identifying inclusion/exclusion criteria and appropriate endpoints. Novel approaches to clinical trial design were discussed to minimize patient exposure to placebo and to reduce the numbers of patients and clinical trials needed for providing substantial evidence. Novel statistical analysis approaches were also discussed to address the inherent challenges of small patient numbers. Areas of urgent unmet need were identified, including the need to develop registries that protect patient identities, to establish close collaboration and communication between the sponsor and regulatory bodies to address methodological and statistical challenges, to collaborate in pre-competitive opportunities within multiple sponsors and in conjunction with academia and disease-specific patient advocacy groups for optimal data sharing, and to develop harmonized guidelines for data extrapolation from source to target pediatric populations. Ultimately, these innovations will help in solving many regulatory challenges in rare disease drug development and encourage the availability of new treatments for patients with rare diseases.