Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Carey Law School, University of Pennsylvania, Philadelphia.
JAMA Health Forum. 2023 Jun 2;4(6):e231313. doi: 10.1001/jamahealthforum.2023.1313.
The US Food and Drug Administration (FDA) has expansive regulatory flexibility regarding the quality and quantity of evidence it deems sufficient to approve new drugs, which has been increasingly used to grant approval based on less certain evidence of benefit. However, the FDA's regulatory flexibility with respect to standards for approval has not been matched by sufficient stringency in its exercise of postmarket safeguards, including the FDA's authority and willingness to require confirmation of benefit through postmarket efficacy studies or to withdraw approval when benefit is not confirmed.
To identify and evaluate opportunities for the FDA to extend its authority to require postmarket efficacy studies and use expedited withdrawal procedures for drugs approved despite substantial residual uncertainty outside the accelerated approval pathway.
The FDA's current approaches to regulatory flexibility with respect to standards for drug approval; examples of shortcomings in the postmarket period; existing statutes and regulations governing the scope of the FDA's authority to impose and enforce postmarket study requirements; and recent legislative reform and agency action regarding the accelerated approval pathway.
Drawing on the broad language of the federal Food, Drug, and Cosmetic Act, the FDA could independently extend its core accelerated approval authorities-required postmarket efficacy studies and expedited withdrawal procedures-to any drug approved with substantial residual uncertainty regarding benefit, such as those supported by a single pivotal trial. To avoid exacerbating existing problems that have become evident during the past 3 decades of experience using the accelerated approval pathway, however, the FDA must ensure that postmarket studies are well designed and completed quickly, while compelling expedited withdrawal when needed.
Under current FDA approaches to drug approval, patients, clinicians, and payers may be left with little confidence about a drug's benefit not only when it first enters the market but also for an extended period thereafter. If policy makers continue to favor earlier market access over evidentiary certainty, flexible approvals must be matched by more expansive use of postmarket safeguards, an approach possible within the FDA's existing legal authorities.
美国食品和药物管理局 (FDA) 在其认为足以批准新药的质量和数量证据方面拥有广泛的监管灵活性，这已被越来越多地用于基于获益证据不太确定的情况下批准新药。然而，FDA 在批准标准方面的监管灵活性并没有与其在实施上市后保障措施方面的严格程度相匹配，包括 FDA 要求通过上市后疗效研究确认获益的权力和意愿，以及在未确认获益时撤销批准的权力。
确定并评估 FDA 扩大其权力的机会，要求进行上市后疗效研究，并在批准药物时使用加速撤市程序，尽管在加速批准途径之外仍存在大量剩余不确定性。
FDA 目前在药物批准标准方面的监管灵活性方法；上市后期间的不足之处的例子；管理 FDA 实施和执行上市后研究要求的权力范围的现有法规和条例；以及最近关于加速批准途径的立法改革和机构行动。
利用联邦《食品、药品和化妆品法》的广泛语言，FDA 可以独立地将其核心加速批准权力——要求进行上市后疗效研究和加速撤市程序——扩展到任何具有大量获益剩余不确定性的药物，例如那些仅由一项关键性试验支持的药物。然而，为了避免加剧过去 30 年来使用加速批准途径所显现的现有问题，FDA 必须确保上市后研究设计良好且迅速完成，同时在需要时强制进行加速撤市。
根据 FDA 目前的药物批准方法，患者、临床医生和支付者可能不仅在药物首次进入市场时，而且在其后很长一段时间内对药物的获益都缺乏信心。如果政策制定者继续青睐更早的市场准入而不是证据确定性，那么灵活的批准必须与更广泛地使用上市后保障措施相匹配，这种方法在 FDA 现有的法律权限内是可行的。
