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

关键路径研究所RFA-FD-20-030提案 摘要 从历史上看，FDA一直将真实世界证据（RWE）作为其工作的关键组成部分， 确保医疗产品安全性的上市后监督和评价。第21 世纪治愈法案要求FDA制定一个框架，以扩大RWD的使用 和RWE支持批准已批准药物的新适应症。通过 利用通过正常医学实践产生的数据，安全性信号， 可以在已经批准的治疗中鉴定新适应症的功效。但随着 大多数现有的RWD是在没有考虑监管标准的情况下生成的， 在确保RWD适用于生成能够告知的RWE方面存在挑战 监管决定。使用现有RWD回答监管问题的努力可以识别 这些挑战和相应的解决方案，但这一奋进需要一个重大的 大量的数据和监管科学专业知识，以充分优化RWD的使用， 可操作的RWE。关键路径研究所（C-Path）拥有数据专业知识， 一个试点项目，以促进使用RWD在新生儿中产生RWE， 广泛适用于其它治疗领域。每年在美国，10%的新生儿 早产，迫切需要提高存活率和结果。但是，在这方面， 新药开发很少，大多数现有药物的证据不足 以支持该高危人群的安全性、有效性和剂量。C-path将利用其 数据协作中心流程和基础架构，用于开发RWD分析 平台将通过与研究者和数据的合作访问RWD 科学家将实施特定的算法和机制，以从 相关来源（汇总数据库和EMR），管理和标准化数据，以及 使分析能够生成可操作的RWE。当远程分析数据时，C-Path将 验证质量保证的处理流程。由此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）目前缺乏可采取行动的参考值 对于常规实验室检查（作为妊娠/产后年龄的函数）和2）缺乏疾病 支气管肺发育不良的进展模型。差距分析将确定关键的经验教训 具体到新生儿，涉及获取、质量、提取、治疗、标准化， RWD分析，以及最佳生成可操作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。由此获得的经验教训 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.