Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Pharmacoepidemiol Drug Saf. 2013 Oct;22(10):1036-45. doi: 10.1002/pds.3478. Epub 2013 Aug 7.
The U.S. Food and Drug Administration (FDA)'s Mini-Sentinel pilot has created a distributed data system with over 125 million lives and nearly 350 million person-years of observation time. The pilot allows the FDA to use modular analytic programs to assess suspected safety signals quickly. The FDA convened a committee to assess the implications of such rapid assessments on subsequent analyses of the same product-outcome pair using the same data. The committee offers several non-binding recommendations based on the strength of the knowledge of the suspected association before running the analysis: signal generation (an analysis with no prior), signal refinement (an analysis with a weak or moderate prior), and signal evaluation (an analysis with a strong prior). The committee believes that modular programs (MPs) are most useful for signal refinement. If MPs are used for analyses with no or weak/moderate priors, the committee members generally agree that the data may be re-used if certain conditions are met. When there is a strong prior, the committee recommends that a protocol-based assessment be used; Mini-Sentinel data may be analyzed by MPs and re-used only under very uncommon circumstances. The committee agrees that any subsequent assessment of the same product-outcome pair that follows an MP analysis should not be interpreted as independent confirmation of the association, such as would be established via replication of the same product-outcome association in two different populations. Instead, the follow-up assessment should be interpreted as an analysis that has reduced insofar as possible systematic errors that may have been present or residual in the original MP analysis. The committee also discussed how this general framework may apply to two completed rapid assessments of dabigatran and bleeding risk and of olmesartan and celiac disease risk.
美国食品和药物管理局 (FDA) 的 Mini-Sentinel 试点项目创建了一个分布式数据系统，涵盖了超过 1.25 亿人的生命和近 3.5 亿人年的观察时间。该试点项目使 FDA 能够使用模块化分析程序快速评估可疑的安全信号。FDA 召集了一个委员会，评估这种快速评估对随后使用相同数据对同一产品-结果组合进行分析的影响。委员会根据在运行分析之前对可疑关联的了解程度提供了几项无约束力的建议：信号生成（无先前分析）、信号细化（先前分析较弱或中等）和信号评估（先前分析较强）。委员会认为，模块化程序 (MPs) 最适合信号细化。如果 MPs 用于无先前或弱/中等先前的分析，委员会成员普遍同意，如果满足某些条件，数据可以重复使用。当存在较强的先前时，委员会建议使用基于协议的评估；只有在非常特殊的情况下，Mini-Sentinel 数据才能通过 MPs 进行分析和重复使用。委员会一致认为，任何随后对同一产品-结果组合的评估，在进行 MPs 分析之后，不应被视为对关联的独立确认，例如通过在两个不同人群中复制相同的产品-结果关联来建立。相反，后续评估应被解释为一种分析，在尽可能减少原始 MPs 分析中可能存在或残留的系统误差。委员会还讨论了这一总体框架如何适用于对达比加群和出血风险以及奥美沙坦和乳糜泻风险的两项已完成的快速评估。
