Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010
Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010
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DOI：
10.1001/jama.2017.5150
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发表时间：
2017-05-09
影响因子：
120.7
通讯作者：
Ross, Joseph S.
中科院分区：
文献类型：
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作者：
Downing, Nicholas S.;Shah, Nilay D.;Ross, Joseph S.
重要性 当新药物和生物制剂在监管部门初步批准批准后发现新的安全风险时，就会发生新药物和生物制剂的上市后安全事件。这些安全事件可以改变新疗法在临床实践中的使用方式，并为患者和临床医生决策提供信息。 目的 描述美国食品和药物管理局 (FDA) 批准的新疗法中上市后安全事件的频率，并检查 FDA 批准时已知的任何新治疗特征是否与风险增加相关。 设计和设置 对 2001 年 1 月 1 日至 2010 年 12 月 31 日 FDA 批准的所有新疗法进行队列研究，随访至 2017 年 2 月 28 日。暴露 FDA 批准时已知的新治疗特征，包括药物类别、治疗领域、优先审查、加速批准、孤儿药状态、接近监管截止日期的批准和监管审查时间。主要结果和措施包括 (1) 因安全问题而撤回，(2) FDA 发布上市后增加的增量黑框警告，以及 (3) FDA 发布安全通信。 结果2001 年至 2010 年，FDA 批准了 222 种新疗法（183 种药物和 39 种生物制剂）。在中位随访期 11.7 年（四分位距 [IQR]，8.7-13.8 年）内，发生了 123 起新的上市后安全事件（3 起撤回、61 起黑框警告和 59 起安全通信），影响了 71 种新疗法（32.0%）。从批准到首次上市后安全事件的中位时间为 4.2 年（IQR，2.5-6.0 年），10 年受上市后安全事件影响的新疗法比例为 30.8%（95% CI，25.1%-37.5%）。在多变量分析中，生物制剂（发生率比 [IRR] = 1.93；95% CI，1.06-3.52；P = 0.03）和精神疾病治疗药物（IRR = 3.78；95% CI，1.77-8.06；P = 0.03）的上市后安全事件在统计学上显着更高。
IMPORTANCE Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making.OBJECTIVES To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk.DESIGN AND SETTING Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017.EXPOSURES Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near-regulatory deadline approval, and regulatory review time.MAIN OUTCOMES AND MEASURES A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications.RESULTS From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8%(95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P =.03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P