London School of Hygiene and Tropical Medicine, London, UK.
BMC Med Res Methodol. 2011 Apr 1;11:36. doi: 10.1186/1471-2288-11-36.
There has been little research on design of studies based on routinely collected data when the clinical endpoint of interest is not recorded, but can be inferred from a prescription. This often happens when exploring the effect of a drug on chronic diseases. Using the LifeLink claims database in studying the possible anti-inflammatory effects of statins in rheumatoid arthritis (RA), oral steroids (OS) were treated as surrogate of inflammatory flare-ups. We compared two cohort study designs, the first using time to event outcomes and the second using quantitative amount of the surrogate.
RA patients were extracted from the LifeLink database. In the first study, patients were split into two sub-cohorts based on whether they were using OS within a specified time window of the RA index date (first record of RA). Using Cox models we evaluated the association between time-varying exposure to statins and (i) initiation of OS therapy in the non-users of OS at RA index date and (ii) cessation of OS therapy in the users of OS at RA index date. In the second study, we matched new statin users to non users on age and sex. Zero inflated negative binomial models were used to contrast the number of days' prescriptions of OS in the year following date of statin initiation for the two exposure groups.
In the unmatched study, the statin exposure hazard ratio (HR) of initiating OS in the 31451 non-users of OS at RA index date was 0.96(95% CI 0.9,1.1) and the statin exposure HR of cessation of OS therapy in the 6026 users of OS therapy at RA index date was 0.95 (0.87,1.05). In the matched cohort of 6288 RA patients the statin exposure rate ratio for duration on OS therapy was 0.88(0.76,1.02). There was digit preference for outcomes in multiples of 7 and 30 days.
The 'time to event' study design was preferable because it better exploits information on all available patients and provides a degree of robustness toward confounding. We found no convincing evidence that statins reduce inflammation in RA patients.
当感兴趣的临床终点未被记录，但可从处方中推断出来时，基于常规收集的数据进行研究设计的研究很少。当探索药物对慢性病的影响时，这种情况经常发生。在使用 LifeLink 索赔数据库研究他汀类药物在类风湿关节炎 (RA) 中的可能抗炎作用时，我们将口服类固醇 (OS) 作为炎症发作的替代指标。我们比较了两种队列研究设计，第一种使用时间事件结果，第二种使用替代物的定量量。
从 LifeLink 数据库中提取 RA 患者。在第一项研究中，根据患者在 RA 索引日期（RA 首次记录）的特定时间窗口内是否使用 OS，将患者分为两个亚组。我们使用 Cox 模型评估了他汀类药物的时间变化暴露与（i）RA 索引日期时未使用 OS 的患者开始使用 OS 治疗以及（ii）RA 索引日期时使用 OS 的患者停止使用 OS 治疗之间的关联。在第二项研究中，我们根据年龄和性别将新的他汀类药物使用者与非使用者相匹配。我们使用零膨胀负二项式模型来对比两组暴露患者在他汀类药物起始后一年中 OS 处方天数。
在未匹配的研究中，在 31451 名 RA 索引日期时未使用 OS 的非使用者中，他汀类药物暴露的起始 OS 风险比 (HR) 为 0.96（95%CI 0.9,1.1），在 RA 索引日期时使用 OS 治疗的 6026 名使用者中，他汀类药物暴露的停止 OS 治疗的 HR 为 0.95（0.87,1.05）。在 6288 名 RA 患者的匹配队列中，OS 治疗持续时间的他汀类药物暴露率比为 0.88（0.76,1.02）。结果存在数字偏好，以 7 天和 30 天的倍数出现。
“时间事件”研究设计更可取，因为它可以更好地利用所有可用患者的信息，并为混杂提供一定程度的稳健性。我们没有发现确凿的证据表明他汀类药物能减轻 RA 患者的炎症。
