Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
RTI Health Solutions, Barcelona, Spain.
Int J Epidemiol. 2020 Oct 1;49(5):1637-1646. doi: 10.1093/ije/dyaa144.
Previous case-control studies have reported a strong association between statin use and lower cancer risk. It is unclear whether this association reflects a benefit of statins or is the result of design decisions that cannot be mapped to a (hypothetical) target trial (that would answer the question of interest).
We outlined the protocol of a target trial to estimate the effect of statins on colorectal cancer incidence among adults with low-density lipoprotein (LDL) cholesterol below 5 mmol/L. We then emulated the target trial using linked electronic health records of 752 469 eligible UK adults (CALIBER 1999-2016) under both a cohort design and a case-control sampling of the cohort. We used pooled logistic regression to estimate intention-to-treat and per-protocol effects of statins on colorectal cancer, with adjustment for baseline and time-varying risk factors via inverse-probability weighting. Finally, we compared our case-control effect estimates with those obtained using previous case-control procedures.
Over the 6-year follow-up, 3596 individuals developed colorectal cancer. Estimated intention-to-treat and per-protocol hazard ratios were 1.00 (95% confidence interval [CI]: 0.87, 1.16) and 0.90 (95% CI: 0.71, 1.12), respectively. As expected, adequate case-control sampling yielded the same estimates. By contrast, previous case-control analytical approaches yielded estimates that appeared strongly protective (odds ratio 0.57, 95% CI: 0.36, 0.91, for ≥5 vs. <5 years of statin use).
Our study demonstrates how to explicitly emulate a target trial using case-control data to reduce discrepancies between observational and randomized trial evidence. This approach may inform future case-control analyses for comparative effectiveness research.
之前的病例对照研究报告称，他汀类药物的使用与较低的癌症风险之间存在很强的关联。目前尚不清楚这种关联是反映了他汀类药物的益处，还是设计决策的结果，这些决策无法映射到（假设的）目标试验（该试验将回答感兴趣的问题）。
我们概述了一项旨在估计 LDL 胆固醇低于 5mmol/L 的成年人使用他汀类药物对结直肠癌发病率影响的目标试验方案。然后，我们使用 752469 名符合条件的英国成年人（CALIBER 1999-2016 年）的电子健康记录，在队列设计和队列病例对照抽样下模拟目标试验。我们使用汇总逻辑回归估计他汀类药物对结直肠癌的意向治疗和方案治疗效果，并通过逆概率加权调整基线和随时间变化的风险因素。最后，我们将我们的病例对照效果估计与以前的病例对照程序获得的估计进行了比较。
在 6 年的随访期间，3596 人发生了结直肠癌。估计的意向治疗和方案治疗风险比分别为 1.00（95%置信区间 [CI]：0.87，1.16）和 0.90（95% CI：0.71，1.12）。正如预期的那样，充分的病例对照抽样得出了相同的估计值。相比之下，以前的病例对照分析方法得出的估计值似乎具有很强的保护作用（比值比 0.57，95%CI：0.36，0.91，用于≥5 年与<5 年他汀类药物使用）。
我们的研究展示了如何使用病例对照数据明确模拟目标试验，以减少观察性和随机试验证据之间的差异。这种方法可能为未来的病例对照分析提供信息，以进行比较有效性研究。
