Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population
Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population
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DOI：
10.1093/aje/kwx287
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发表时间：
2018-04-01
影响因子：
5
通讯作者：
Sturmer, Til
中科院分区：
文献类型：
--
作者：
Hong, Jin-Liern;Funk, Michele Jonsson;Sturmer, Til
根据多国试验的结果，他汀类药物可用于高敏C反应蛋白水平升高和正常低密度脂蛋白胆固醇水平的患者，这项多国试验的结果是，在预防中使用他汀类药物的理由：评估罗舒伐他汀(Jupiter)的干预试验(2003-2008)，但在现实世界人群中的益处尚不清楚。我们试图使用2001-2014年英国临床实践研究数据链(CPRD)的数据将Jupiter结果推广到符合试验条件的人群。我们将CPRD人群缺失的基线特征相乘，并根据观察值和推测值选择符合试验条件的参与者作为目标人群。试验参与者根据个人预测的被选入试验的概率被加权为代表红十字委员会人口(n=383,418)。试验参与者也被标准化为无遗漏值的红十字委员会人口(n=2,677)。在JUPITER，瑞舒伐他汀降低了心血管风险，3年风险差异为-2.0%(95%可信区间：-2.9，-1.1)。瑞舒伐他汀的效应在头2年较弱，但标准化后3年仍较强，分别为CPRD人群(3年风险差异=-2.7%；95%CI：-5.8，0.4)和无缺失数据的CPRD人群(3年风险差异=-1.7%；95%CI：-3.5，0.1)。由于缺少纳入/排除标准方面的数据，这项研究说明了利用真实世界数据库理解试验概括性的可能方法。
Statins are indicated in patients with elevated levels of high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol based on results of the multicountry trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) (2003-2008), but the benefit in real-world populations remains unknown. We sought to generalize JUPITER results to trial-eligible population using data from the UK Clinical Practice Research Datalink (CPRD), 2001-2014. We multiply imputed missing baseline characteristics for the CPRD population and selected the trial-eligible participants as the target population based on observed and imputed values. Trial participants were weighted to be representative of the CPRD population (n = 383,418) based on individual predicted probability of selection into the trial. Trial participants were also standardized to the CPRD population without missing values (n = 2,677). In JUPITER, rosuvastatin reduced cardiovascular risk with a 3-year risk difference of -2.0% (95% confidence interval (CI): -2.9, -1.1). The rosuvastatin effect was muted in the first 2 years but remained strong at 3 years after standardizing to the imputed CPRD population (3-year risk difference = -2.7%; 95% CI: -5.8, 0.4) and the CPRD population without missing data (3-year risk difference= -1.7%; 95% CI: -3.5, 0.1). The study serves as an illustration of possible approaches to understanding generalizability of trials using real-world databases given limitations due to missing data on inclusion/exclusion criteria.