Background/Aims

The US Food and Drug Administration outlines clinical studies as postmarketing requirements and commitments to be fulfilled following approval of new drugs and biologics (“therapeutics”). Regulators have increasingly emphasized lifecycle evaluation of approved therapeutics, and postmarketing studies are intended to advance our understanding of therapeutic safety and efficacy. However, little is known about the indications that clinical studies outlined in postmarketing requirements and commitments investigate, including whether they are intended to generate evidence for approved or other clinical indications. Therefore, we characterized US Food and Drug Administration postmarketing requirements and commitments for new therapeutics approved from 2009 to 2018.

Methods

We conducted a cross-sectional study of all novel therapeutics, including small-molecule drugs and biologics, receiving original US Food and Drug Administration approval from 2009 to 2018, using approval letters accessed through the [email protected] database. Outcomes included the number and characteristics of US Food and Drug Administration postmarketing requirements and commitments for new therapeutics at original approval, including the types of studies outlined, the indications to be investigated, and the clinical evidence to be generated.

Results

From 2009 to 2018, the US Food and Drug Administration approved 343 new therapeutics with 1978 postmarketing requirements and commitments. Overall, 750 (37.9%) postmarketing requirements and commitments outlined clinical studies. For 71 of 343 (20.7%) therapeutics, no postmarketing requirements or commitments for clinical studies were outlined, while at least 1 was outlined for 272 (79.3%; median 2 (interquartile range: 1–4)). Among these 272 therapeutics, the number of postmarketing requirements and commitments for clinical studies per therapeutic did not change from 2009 (median: 2 (interquartile range: 1–4)) to 2018 (median: 2 (interquartile range: 1–3)). Among the 750 postmarketing requirements and commitments for clinical studies, 448 (59.7%) outlined new prospective cohort studies, registries, or clinical trials, while the remainder outlined retrospective studies, secondary analyses, or completion of ongoing studies. Although 455 (60.7%) clinical studies investigated only original approved therapeutic indications, 123 (16.4%) enrolled from an expansion of the approved disease population and 61 (8.1%) investigated diseases unrelated to approved indications.

Conclusions

The US Food and Drug Administration approves most new therapeutics with at least 1 postmarketing requirement or commitment for a clinical study, and outlines investigations of safety or efficacy for both approved and unapproved indications. The median number of 2 clinical studies outlined has remained relatively constant over the last decade. Given increasing emphasis by the US Food and Drug Administration on faster approval and lifecycle evaluation of therapeutics, these findings suggest that more postmarketing requirements and commitments may be necessary to address gaps in the clinical evidence available for therapeutics at approval.

中文翻译：

---

美国食品和药物管理局对上市后要求和上市后承诺的利用，2009-2018

背景/目标

美国食品和药物管理局将临床研究概述为新药和生物制剂（“治疗药物”）获批后应履行的上市后要求和承诺。监管机构越来越强调对已批准疗法的生命周期评估，上市后研究旨在促进我们对治疗安全性和有效性的理解。然而，对于上市后要求和承诺中概述的临床研究调查的适应症知之甚少，包括它们是否旨在为已批准的或其他临床适应症提供证据。因此，我们描述了美国食品和药物管理局对 2009 年至 2018 年批准的新疗法的上市后要求和承诺。

方法

我们使用通过 [电子邮件保护] 数据库访问的批准信，对包括小分子药物和生物制剂在内的所有新疗法进行了横断面研究，并在 2009 年至 2018 年期间获得了美国食品和药物管理局的原始批准。结果包括美国食品和药物管理局在最初批准时对新疗法的上市后要求和承诺的数量和特征，包括概述的研究类型、要研究的适应症和要产生的临床证据。

结果

从 2009 年到 2018 年，美国食品和药物管理局根据 1978 年的上市后要求和承诺批准了 343 种新疗法。总体而言，750 (37.9%) 项上市后要求和承诺概述了临床研究。对于 343 种疗法中的 71 种（20.7%），没有概述临床研究的上市后要求或承诺，而 272 种疗法中至少概述了 1 种（79.3%；中位数 2（四分位距：1-4））。在这 272 种疗法中，每种疗法的上市后要求和临床研究承诺的数量从 2009 年（中位数：2（四分位距：1-4））到 2018 年（中位数：2（四分位距：1-3））没有变化. 在 750 项临床研究的上市后要求和承诺中，448 项（59.7%）概述了新的前瞻性队列研究、登记或临床试验，而其余的则概述了回顾性研究、二次分析或正在进行的研究的完成。尽管 455 项 (60.7%) 临床研究仅调查了最初批准的治疗适应症，但 123 项 (16.4%) 来自批准的疾病人群的扩大，61 项 (8.1%) 调查了与批准的适应症无关的疾病。

结论

美国食品和药物管理局批准了大多数新疗法，其中至少有一项临床研究的上市后要求或承诺，并概述了对已批准和未批准适应症的安全性或有效性调查。在过去十年中，概述的 2 项临床研究的中位数保持相对稳定。鉴于美国食品和药物管理局越来越重视治疗药物的更快批准和生命周期评估，这些研究结果表明，可能需要更多的上市后要求和承诺来解决批准时治疗药物可用的临床证据中的空白。