Increasing levels of restriction in pharmacoepidemiologic database studies of elderly and comparison with randomized trial results
Increasing levels of restriction in pharmacoepidemiologic database studies of elderly and comparison with randomized trial results
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DOI：
10.1097/mlr.0b013e318070c08e
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发表时间：
2007-10-01
期刊：
影响因子：
3
通讯作者：
Glynn, Robert J.
中科院分区：
文献类型：
--
作者：
Schneeweiss, Sebastian;Patrick, Amanda R.;Glynn, Robert J.
背景资料：限制研究人群的目标是使患者在潜在混杂因素和治疗效果方面更加同质，从而实现更小的偏倚效果估计。目的：本文描述了药物流行病学中使用的限制水平的增加，并检查了它们在多大程度上改变了他汀类药物治疗和1年死亡率研究中的比率估计值并减少了偏倚。方法：研究队列来自1995年至2002年期间参加Medicare和宾夕法尼亚州老年人药物援助合同（PACE）的65岁及以上老年人。我们确定了研究期间所有他汀类药物的使用者，并评估了一年内死亡的时间。应用了以下渐进限制：（1）仅研究事件药物使用者，（2）选择与干预组最相似的对照组，（3）排除有禁忌症的患者，（4）排除依从性低的患者，（5）限制随机试验（RCT）中代表的特定高风险/低风险亚组。基础队列包括122，406名他汀类药物使用者，平均年龄78岁，主要是白色（93%），他汀类药物使用者的未校正率比为0.32。当应用所有5项限制时（N = 11，673），未调整率比增加至0.72。多变量考克斯回归校正率比从0.62 [95%置信区间（CI），0.58 - 0.66]增加至0.79（95% CI，0.60 - 1.03）。然而，在前3个限制后，效应量变化不大。最终估计值与在65岁及以上患者中进行的3项普伐他汀RCT的汇总估计值相似。我们认为，限制I通过4妥协generalizability little.Conclusions：在我们的一个大型数据库研究的例子中，限制事件吸毒者，类似的比较组，没有禁忌症的患者，并遵守患者是一个切实可行的策略，这限制了混杂的影响，因为这些方法产生的结果更接近随机对照试验中看到的。
Background: The goal of restricting study populations is to make patients more homogeneous regarding potential confounding factors and treatment effects and thereby achieve less biased effect estimates.Objectives: This article describes increasing levels of restrictions for use in pharmacoepidemiology and examines to what extent they change rate ratio estimates and reduce bias in a study of statin treatment and 1-year mortality.Methods: The study cohort was drawn from a population of seniors age 65 years and older enrolled in both Medicare and the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE) between 1995 and 2002. We identified all users of statins during the study period and assessed the time until death within I year. The following progressive restrictions were applied: (1) study incident drug users only, (2) choose a comparison group most similar to the intervention group, (3) exclude patients with contraindications, (4) exclude patients with low adherence, and (5) restrict to specific high-risk/low-risk subgroups represented in randomized trails (RCTs).Results: The basic cohort comprised 122,406 statin users, who were on average 78 years old and predominantly white (93%) and showed an unadjusted rate ratio of 0.32 for statin users. When all 5 restrictions were applied (N = 11,673), the unadjusted rate ratio had increased to 0.72. Multivariable Cox regression adjusted rate ratios increased from 0.62 [95% confidence interval (CI), 0.58-0.66] to 0.79 (95% Cl, 0.60-1.03). However, after the first 3 restrictions the effect size changed little. The final estimate is similar to that obtained as a pooled estimate of 3 pravastatin RCTs in patients age 65 years and older. We argue that restrictions I through 4 compromised generalizability little.Conclusions: In our example of a large database study, restricting to incident drug users, similar comparison groups, patients without contraindication, and to adherent patients was a practical strategy, which limited the effect of confounding, as these approaches yield results closer to those seen in RCTs.