Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions

We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2–10 months for known ADRs and 19–44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0–122.5 days and 185.5–306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.

本研究通过对比美国药品上市初期后已知与未知药品不良反应（ADR）的报告时间差异，探究影响信号检测时机的相关因素。本研究采用提交至美国食品药品监督管理局（FDA）的不良事件反应（AERs）数据，针对与6种药物（瑞舒伐他汀、阿立哌唑、特立帕肽、泰利霉素、艾塞那肽、伐尼克兰）相关的6例药品不良反应展开分析：以比例报告比、报告比值比及信息组分作为信号检测指标，在各药品上市后每3个月跟踪其变化情况，并对信号检测时长进行研究。美国地区药品上市后，已知ADR的信号检测时长为2~10个月，未知ADR则为19~44个月；已知与未知ADR的中位滞后时间分别为99.0~122.5天与185.5~306.0天。当FDA发布针对某未知ADR的罕见但潜在严重健康风险的警示信息后，从药品不良反应发生到提交至FDA的报告滞后时间会更短。本研究表明，影响信号检测时长的一项关键因素为药品上市时该不良反应是否为已知的药品不良反应。