Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study.
Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study.
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DOI：
10.1136/bmj.h4633
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发表时间：
2015-09-23
期刊：
影响因子：
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通讯作者：
Darrow JJ
中科院分区：
文献类型：
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作者：
Kesselheim AS;Wang B;Franklin JM;Darrow JJ
目的 评估过去二十年来美国食品和药物管理局对特殊快速开发和审查途径的使用情况。设计队列研究。设置 FDA 在 1987 年至 2014 年间批准的新疗法。 人群 公开来源提供了每种药物的批准年份、创新性（同类首创与非同类首创）、世界卫生组织解剖治疗分类，以及 FDA 的四个主要加速开发和审查计划或指定中的哪一个（如果有）与每种药物相关：孤儿药、快速通道、加速批准和优先审查。主要结果指标 Logistic 回归模型评估了与四个加速开发和审查计划中的每一个相关的药物比例的趋势。为了评估随时间推移与每种批准药物相关的项目数量，采用了泊松模型，其中项目数量作为因变量，线性项表示批准年份。比较了一流药物和非一流药物之间的趋势差异。结果 FDA 在研究期间批准了 774 种药物，其中三分之一代表一流药物。优先审查 (43%) 是四个计划中最普遍的，加速批准 (9%) 最不常见。授予每种新批准药物的快速审评和批准项目数量每年显着增加 2.6%（发生率 1.026，95% 置信区间 1.017 至 1.035，P<0.001），并且与至少一个此类项目相关的药物比例增加 2.4%（比值比 1.024，95% 置信区间 1.006 至1.043，P=0.009）。推动这一趋势的是与至少一个药物计划相关的已批准非同类药物比例的增加（相互作用 P=0.03）。结论 在过去二十年中，FDA 新批准的药物与越来越多的加速开发或审评项目相关。尽管加速计划应严格限于提供显着临床进展的药物，但这一趋势是由非同类首创药物（因此可能缺乏创新性）推动的。
Objective To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Design Cohort study. Setting FDA approved novel therapeutics between 1987 and 2014. Population Publicly available sources provided each drug’s year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA’s four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review. Main outcome measures Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not. Results The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P<0.001), and a 2.4% increase in the proportion of drugs associated with at least one such program (odds ratio 1.024, 95% confidence interval 1.006 to 1.043, P=0.009). Driving this trend was an increase in the proportion of approved, non-first in class drugs associated with at least one program for drugs (P=0.03 for interaction). Conclusions In the past two decades, drugs newly approved by the FDA have been associated with an increasing number of expedited development or review programs. Though expedited programs should be strictly limited to drugs providing noticeable clinical advances, this trend is being driven by drugs that are not first in class and thus potentially less innovative.