Evaluating short-term drug effects using a physician-specific prescribing preference as an instrumental variable
Evaluating short-term drug effects using a physician-specific prescribing preference as an instrumental variable
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DOI：
10.1097/01.ede.0000193606.58671.c5
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发表时间：
2006-05-01
期刊：
影响因子：
5.4
通讯作者：
Schneeweiss, S
中科院分区：
文献类型：
--
作者：
Brookhart, MA;Wang, PS;Schneeweiss, S
背景：对处方药的安全性和有效性进行上市后的观察性研究是至关重要的，但也存在方法学问题。可用于这类研究的数据来源往往缺乏关于所研究药物暴露的适应症和其他重要混杂因素的信息。在治疗效果的非实验研究中，仪器变量方法被认为是一种潜在的控制适应症混淆的方法；然而，很难找到好的工具。方法：我们提出了一种用于药物表皮学的仪器，该仪器基于对处方医生相对于竞争疗法对一种药物的偏好的时变估计。结果：在对17个潜在的混杂因素进行常规多变量回归校正后，我们发现在最初接触COX-2的120天内使用COX-2没有保护作用(风险差=-0.06每100名患者；95%可信区间=-0.26至0.14)。然而，建议的工具变量方法将保护作用归因于COX-2暴露(-1.31/100名患者；-2.42至-0.20)，与随机试验结果(-0.65/100名患者；-1.08至-0.22)一致。结论：我们提出的工具变量方法似乎大大减少了由于未观察到的混杂造成的偏差。然而，需要做更多的工作来了解这种方法对可能违反工具变量假设的敏感性。
Background: Postmarketing observational studies of the safety and effectiveness of prescription medications are critically important but fraught with methodological problems. The data sources available for such research often lack information on indications and other important confounders for the drug exposure under study. Instrumental variable methods have been proposed as a potential approach to control confounding by indication in nonexperimental studies of treatment effects; however, good instruments are hard to find.Methods: We propose an instrument for use in pharmacoepidermology that is based on a time-varying estimate of the prescribing physician's preference for one drug relative to a competing therapy. The use of this instrument is illustrated in a study comparing the effect of exposure to COX-2 inhibitors with nonselective, nonsteroidal anti-inflammatory medications on gastrointestinal complications.Results: Using conventional multivariable regression adjusting for 17 potential confounders, we found no protective effect due to COX-2 use within 120 days from the initial exposure (risk difference = -0.06 per 100 patients; 95% confidence interval = -0.26 to 0.14). However, the proposed instrumental variable method attributed a protective effect to COX-2 exposure (-1.31 per 100 patients; -2.42 to -0.20) compatible with randomized trial results (-0.65 per 100 patients; -1.08 to -0.22).Conclusions: The instrumental variable method that we have proposed appears to have substantially reduced the bias due to unobserved confounding. However, more work needs to be done to understand the sensitivity of this approach to possible violations of the instrumental variable assumptions.