Faculties of Medicine and Law, Dalhousie University.
Milbank Q. 2019 Sep;97(3):820-857. doi: 10.1111/1468-0009.12413. Epub 2019 Aug 12.
Policy Points The US Food and Drug Administration (FDA) has in recent years allowed onto the market several drugs with limited evidence of safety and effectiveness, provided that manufacturers agree to carry out additional studies while the drugs are in clinical use. Studies suggest that these postmarketing requirements (PMRs) frequently lack transparency, are subject to delays, and fail to answer the questions of greatest clinical importance. Yet, none of the literature speaks directly to the challenges that the FDA-as a regulatory institution-encounters in enforcing PMRs. Through a series of interviews with FDA leadership, this article analyzes and situates those challenges in the midst of political threats to the FDA's public health mandate.
Modern pharmaceutical regulation is premised on a rigorous examination of a drug's safety and effectiveness prior to its lawful sale. However, since the 1990s, the US Food and Drug Administration (FDA) has gradually shifted to a model of "lifecycle" regulation that increasingly relies on postmarketing requirements (PMRs) to encourage studies of drug safety and effectiveness following regulatory approval. This article examines the range of legal, institutional, and political challenges that FDA faces in the context of lifecycle regulation.
Document-based legal and policy analysis was combined with a set of semistructured interviews of current and former FDA officials (n = 23) in order to explore the implications of the FDA's use of PMRs. The median interview time per official was 61 minutes, with a range of 24 to 227 minutes. All of the officials interviewed occupied positions of leadership and influence within the FDA, such as directors of an FDA center or office, key legal counsel on agency-wide policy initiatives, and the commissioner of the FDA.
Insufficient resources and coordination within the FDA, inadequate legal authorities, and the political economy of withdrawing an approved indication in the face of opposition from companies and patients all contribute to the observed shortcomings in the FDA's use and enforcement of PMRs. Further, the FDA is fully aware of these challenges, yet is seemingly resigned to and resistant to criticism of its use of PMRs.
This study of the FDA's shift toward lifecycle regulation reveals not simply an agency in transition, but rather an agency on guard against a set of larger political threats to its mandate. This can be characterized as a state of institutional incumbency in which the agency is engaged in an effort to reproduce key features of the regulatory system-in concert with regulated industries and others-while simultaneously sanctioning significant changes to the regulatory standards the FDA has long applied, to the detriment of public health.
政策要点 美国食品和药物管理局（FDA）近年来允许一些安全性和有效性证据有限的药物上市，前提是制造商同意在药物临床使用期间进行额外的研究。研究表明，这些上市后要求（PMRs）经常缺乏透明度，会延迟，并且无法回答最重要的临床问题。然而，没有一篇文献直接讨论 FDA 作为监管机构在执行 PMRs 时遇到的挑战。通过对 FDA 领导层的一系列采访，本文分析并将这些挑战置于对 FDA 公共卫生任务的政治威胁之中。
现代药物监管基于在合法销售之前对药物的安全性和有效性进行严格检查。然而，自 20 世纪 90 年代以来，美国食品和药物管理局（FDA）已逐渐转向“生命周期”监管模式，越来越依赖上市后要求（PMRs）来鼓励监管批准后对药物安全性和有效性的研究。本文探讨了 FDA 在生命周期监管背景下面临的一系列法律、机构和政治挑战。
结合对当前和前任 FDA 官员（n=23）的一系列半结构化采访的文档为基础的法律和政策分析，以探讨 FDA 使用 PMRs 的含义。每位官员的平均访谈时间为 61 分钟，范围为 24 至 227 分钟。所有接受采访的官员都在 FDA 担任领导和有影响力的职位，例如 FDA 中心或办公室主任、机构范围内政策倡议的主要法律顾问以及 FDA 专员。
FDA 内部资源和协调不足、法律授权不足以及在面对公司和患者的反对时撤回已批准的适应症的政治经济因素，都导致了 FDA 对 PMRs 的使用和执行方面存在的明显缺陷。此外，FDA 完全意识到这些挑战，但似乎对其使用 PMRs 持批评态度。
对 FDA 向生命周期监管的转变的研究不仅揭示了一个转型中的机构，而且揭示了一个机构对其任务的一系列更大的政治威胁保持警惕。这可以被描述为一种机构在职状态，其中该机构与受监管行业和其他机构合作，努力复制监管系统的关键特征，同时对 FDA 长期适用的监管标准进行重大更改，以牺牲公共卫生为代价。
