Advancing standards and methodologies to generate real world evidence from real world data through a neonatal pilot project

RFA-FD-20-030的关键路径研究所建议 摘要 从历史上看，FDA一直将真实世界证据(RWE)作为其努力的关键组成部分 确保医疗产品安全的上市后监控和评估。21号 世纪治疗法案要求FDA开发一个框架，扩大RWD的使用 和莱茵支持批准已经批准的药物的新适应症。通过 利用通过正常医疗实践产生的数据、安全信号和 新适应症的疗效可以在已经批准的治疗中确定。然而，由于 大多数现有的RWD是在没有考虑监管标准的情况下产生的，意义重大 存在的挑战是确保RWD适合于生成能够提供信息的RWE 监管决定。利用现有的RWD回答监管问题的努力可以确定 这些挑战和相应的解决方案，但这一努力需要显著的 数据量和监管科学专业知识，以充分优化RWD的使用，以提取 可起诉的莱茵集团。关键路径研究所(C-PATH)拥有数据专业知识，并将执行 一个试点项目，以促进使用可再生能源在新生儿中产生可再生能源，并从中吸取教训 广泛适用于其他治疗领域。在美国，每年有10%的新生儿 早产儿早产，迫切需要提高存活率和结局。然而， 新药开发很少，而且大多数现有药物证据不足。 以支持这一高危人群的安全性、有效性和剂量。C-Path将利用其 开发RWD Analytics的数据协作中心流程和基础设施 站台。RWD将通过与调查人员和数据的合作来访问 科学家。将实施特定的算法和机制来提取RWD 相关来源(聚合数据库和EMR)，管理和标准化数据，以及 启用分析以生成可操作的RWE。远程分析数据时，C-Path将 验证处理工作流以确保质量。这样提取的数据将解决两个问题 新生儿人口中未得到满足的主要需求：1)目前缺乏可操作的参考值 常规实验室检查(作为孕期/出生后年龄的函数)和2)无疾病 支气管肺发育不良的进展模型。差距分析将找出主要教训 具体到新生儿，与获取、质量、提取、护理、标准化和 对RWD的分析，以及确定的以最佳方式生成可操作RWE的潜在解决方案， 并与新生儿社区的主要利益相关者分享。从这件事中吸取的教训 然后，高危人群可以推广到其他治疗领域。

Critical Path Institute Proposal for RFA-FD-20-030 ABSTRACT Historically, FDA has utilized real-world evidence (RWE) as a key component of its efforts to assure post-marketing surveillance and evaluation of medical product safety. The 21st Century Cures Act mandates FDA to develop a framework that expands the use of RWD and RWE to support approvals of a new indications for an already approved drug. By leveraging data generated through the normal practice of medicine, signals of safety and efficacy for new indications can be identified in already approved therapies. However, as most existing RWD was generated without the regulatory standards in mind, significant challenges exist to ensure RWD is fit-for-purpose to generate RWE capable of informing regulatory decisions. Efforts to use existing RWD to answer regulatory questions can identify these challenges and corresponding solutions, but this endeavor requires a significant amount of data and regulatory science expertise to fully optimize the use of RWD to extract actionable RWE. The Critical Path Institute (C-Path) has that data expertise and will execute a pilot project to facilitate the use of RWD to generate RWE in neonates, with learnings being broadly applicable to other therapeutic areas. Each year in the U.S., 10% of neonates are born preterm and there is an urgent need to improve survival and outcome. However, there is minimal new drug development and most existing drugs have insufficient evidence to support safety, efficacy, and dosage in this high-risk population. C-path will leverage its Data Collaboration Center processes and infrastructure to develop an RWD Analytics Platform. RWD will be accessed through collaborations with investigators and data scientists. Specific algorithms and mechanisms will be implemented to extract RWD from relevant sources (aggregated databases and EMRs), curate and standardize data, and enable analyses to generate actionable RWE. When data are analyzed remotely, C-Path will validate processing workflows for quality assurance. Data thus extracted will address two key unmet needs in the neonatal population: 1) current lack of actionable reference values for routine laboratory tests (as a function of gestational/postnatal age) and 2) lack of disease progression model for bronchopulmonary dysplasia. A gaps analysis will identify key lessons specific to neonates relating to the access, quality, extraction, curation, standardization, and analysis of RWD, and potential solutions to optimally generate actionable RWE identified, and shared with key stakeholders in the neonatal community. Lessons learned with this high-risk population can then be generalized to other therapeutic areas.