Bennett Charles L, Nebeker Jonathan R, Yarnold Paul R, Tigue Cara C, Dorr David A, McKoy June M, Edwards Beatrice J, Hurdle John F, West Dennis P, Lau Denys T, Angelotta Cara, Weitzman Sigmund A, Belknap Steven M, Djulbegovic Benjamin, Tallman Martin S, Kuzel Timothy M, Benson Al B, Evens Andrew, Trifilio Steven M, Courtney D Mark, Raisch Dennis W
Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Arch Intern Med. 2007 May 28;167(10):1041-9. doi: 10.1001/archinte.167.10.1041.
The Food and Drug Administration (FDA) and pharmaceutical manufacturers conduct most postmarketing pharmaceutical safety investigations. These efforts are frequently based on data mining of databases. In 1998, investigators initiated the Research on Adverse Drug events And Reports (RADAR) project to investigate reports of serious adverse drug reactions (ADRs) and prospectively obtain information on these cases. We compare safety efforts for evaluating serious ADRs conducted by the FDA and pharmaceutical manufacturers vs the RADAR project.
We evaluated the completeness of serious ADR descriptions in the FDA and RADAR databases and the comprehensiveness of notifications disseminated by pharmaceutical manufacturers and the RADAR investigators. A serious ADR was defined as an event that led to death or required intensive therapies to reverse.
The RADAR investigators evaluated 16 serious ADRs. Compared with descriptions of these ADRs in FDA databases (2296 reports), reports in RADAR databases (472 reports) had a 2-fold higher rate of including information on history and physical examination (92% vs 45%; P<.001) and a 9-fold higher rate of including basic science findings (34% vs 4%; P = .08). Safety notifications were disseminated earlier by pharmaceutical suppliers (2 vs 4 years after approval, respectively), although notifications were less likely to include information on incidence (46% vs 93%; P = .02), outcomes (8% vs 100%; P<.001), treatment or prophylaxis (25% vs 93%; P<.001), or references (8% vs 80%; P<.001).
Proactive safety efforts conducted by the RADAR investigators are more comprehensive than those conducted by the FDA and pharmaceutical manufacturers, but dissemination of related safety notifications is less timely.
美国食品药品监督管理局（FDA）和制药企业开展了大部分上市后药品安全性调查。这些工作通常基于数据库的数据挖掘。1998年，研究人员启动了药品不良事件及报告研究（RADAR）项目，以调查严重药品不良反应（ADR）报告，并前瞻性地获取这些病例的信息。我们比较了FDA、制药企业以及RADAR项目在评估严重ADR方面的安全性工作。
我们评估了FDA和RADAR数据库中严重ADR描述的完整性，以及制药企业和RADAR研究人员发布通知的全面性。严重ADR被定义为导致死亡或需要强化治疗以逆转的事件。
RADAR研究人员评估了16例严重ADR。与FDA数据库中这些ADR的描述（2296份报告）相比，RADAR数据库中的报告（472份报告）包含病史和体格检查信息的比例高出2倍（92%对45%；P<0.001），包含基础科学发现的比例高出9倍（34%对4%；P = 0.08）。制药供应商更早发布了安全通知（分别在批准后2年和4年），尽管通知包含发病率信息的可能性较小（46%对93%；P = 0.02），包含结局信息的可能性较小（8%对100%；P<0.001），包含治疗或预防信息的可能性较小（25%对93%；P<0.001），包含参考文献的可能性较小（8%对80%；P<0.001）。
RADAR研究人员开展的主动安全性工作比FDA和制药企业更全面，但相关安全通知的发布不够及时。
