Pharmacoepidemiology and Pharmacovigilance Division, Medicines for Human Use Department, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.
Pharmacoepidemiol Drug Saf. 2022 Mar;31(3):294-301. doi: 10.1002/pds.5374. Epub 2021 Nov 8.
Liver injury is an important identified risk for agomelatine and several measures were put in place to prevent and minimize such risk. The study aims to assess the impact of four interventions on the incidence of agomelatine use, particularly among patients aged ≥75 in Spain between 2011 and 2018.
Quasi-experimental interrupted time-series analysis to examine data from a nationwide electronic healthcare record database (BIFAP). Quarterly cumulative incidence of agomelatine use per 100 000 patients was calculated and the impact of four regulatory interventions was quantified.
The incidence of agomelatine use decreased by 85% and 87% from first quarter 2011 to last quarter 2018 in patients below and above 75 years old, respectively. Regulatory actions taken were not associated with an immediate and significant falling level of use or slope. The incidence was less than expected 6 months after the first and third intervention for patients below and above 75 years old, and more than expected after the second and fourth intervention for both populations, though these analyses were underpowered to observe significant results. The downward trend became less pronounced, reaching a residual level of use, which remained stable in the last segment of the study period.
New users of agomelatine decreased throughout the study period, starting before interventions took place. The effect of specific interventions might be masked by the progressive decrease tendency, constant over the study period. The effects of external factors that might overlap, unintended consequences, and issues concerning statistical modeling in situations where rates are already falling, should be considered when interpreting the results.
肝损伤是阿戈美拉汀的一个重要确定风险，为此采取了多项措施来预防和尽量减少这种风险。本研究旨在评估四项干预措施对阿戈美拉汀使用发生率的影响，特别是在西班牙年龄≥75 岁的患者中。
采用准实验性中断时间序列分析，对全国性电子医疗记录数据库（BIFAP）的数据进行分析。计算每 10 万名患者中阿戈美拉汀使用的季度累积发生率，并量化四项监管干预的影响。
在年龄<75 岁和≥75 岁的患者中，阿戈美拉汀的使用发生率从 2011 年第一季度到 2018 年最后一个季度分别下降了 85%和 87%。采取的监管措施与使用水平的立即显著下降或斜率无关。在年龄<75 岁和≥75 岁的患者中，第一次和第三次干预后 6 个月内，发生率低于预期，而第二次和第四次干预后，两个年龄段的发生率均高于预期，但这些分析结果因样本量不足而无法观察到显著结果。下降趋势变得不那么明显，达到了一个剩余的使用水平，在研究后期保持稳定。
在干预措施实施之前，新使用阿戈美拉汀的患者数量在整个研究期间持续减少。特定干预措施的效果可能被逐渐下降的趋势所掩盖，这种趋势在研究期间保持不变。在已经下降的情况下，应该考虑解释结果时应考虑外部因素的影响、意外后果以及与统计模型相关的问题。
