Grosso Anthony, Douglas Ian, Hingorani Aroon, MacAllister Raymond, Smeeth Liam
Department of Pharmacy, University College London Hospitals NHS Foundation Trust, London, UK.
Br J Clin Pharmacol. 2008 Nov;66(5):689-94. doi: 10.1111/j.1365-2125.2008.03273.x. Epub 2008 Jul 31.
Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care population.
We used the UK General Practice Research Database to assess the risk of several recently reported adverse events linked to the use of strontium ranelate for osteoporosis in postmenopausal women. The self-controlled case-series method was used to minimize the potential for biases in the quantification of risk estimates.
Age-adjusted rate ratios for venous thromboembolism, gastrointestinal disturbance, minor skin complaint and memory loss were 1.1 [95% confidence interval (CI) 0.2, 5.0], 3.0 (95% CI 2.3, 3.8), 2.0 (95% CI 1.3, 3.1) and 1.8 (95% CI 0.2, 14.1), respectively. No cases of osteonecrosis of the jaw, toxic-epidermal necrosis, Stevens-Johnson syndrome or drug rash with eosinophilia and systemic symptoms were found.
Although we confirmed the association between strontium ranelate and adverse events identified in the Phase III publications, there was no evidence of an association between strontium ranelate and the aforementioned potentially life-threatening adverse events. Our study demonstrates the relative ease with which this method can assess a variety of adverse events associated with a new drug in actual clinical practice. We believe this technique could be more widely adopted to assess the safety profile of new drugs.
药品获批上市后，药物安全性评估在很大程度上依赖于对不良反应的零星、自发报告的整理。本研究旨在评估一种更系统的方法在检测不良事件方面的潜在效用，该方法利用从大量基层医疗人群中常规收集的临床数据。
我们使用英国全科医疗研究数据库评估了几种最近报道的与绝经后妇女使用雷奈酸锶治疗骨质疏松症相关的不良事件风险。采用自身对照病例系列法以尽量减少风险估计量化过程中产生偏差的可能性。
静脉血栓栓塞、胃肠道紊乱、轻微皮肤问题和记忆力减退的年龄调整率比分别为1.1 [95%置信区间（CI）0.2，5.0]、3.0（95% CI 2.3，3.8）、2.0（95% CI 1.3，3.1）和1.8（95% CI 0.2，14.1）。未发现颌骨坏死、中毒性表皮坏死松解症、史蒂文斯 - 约翰逊综合征或伴有嗜酸性粒细胞增多和全身症状的药疹病例。
尽管我们证实了雷奈酸锶与III期出版物中确定的不良事件之间的关联，但没有证据表明雷奈酸锶与上述潜在危及生命的不良事件之间存在关联。我们的研究表明，在实际临床实践中，这种方法能够相对轻松地评估与新药相关的各种不良事件。我们认为这种技术可以更广泛地用于评估新药的安全性概况。
