Abstract：
The self-controlled case-series (SCCS) research design is increasingly used in pharmacoepidemiologic studies of drug-drug interactions (DDIs), with the target of inference being the incidence rate ratio (IRR) associated with concomitant exposure to the object plus precipitant drug versus the object drug alone. While day-level drug exposure can be inferred from dispensing claims, these inferences may be inaccurate, leading to biased IRRs. Grace periods (periods assuming continued treatment impact after days\' supply exhaustion) are frequently used by researchers, but the impact of grace period decisions on bias from exposure misclassification remains unclear. Motivated by an SCCS study examining the potential DDI between clopidogrel (object) and warfarin (precipitant), we investigated bias due to precipitant or object exposure misclassification using simulations. We show that misclassified precipitant treatment always biases the estimated IRR toward the null, whereas misclassified object treatment may lead to bias in either direction or no bias, depending on the scenario. Further, including a grace period for each object dispensing may unintentionally increase the risk of misclassification bias. To minimize such bias, we recommend 1) avoiding the use of grace periods when specifying object drug exposure episodes; and 2) including a washout period following each precipitant exposed period.
摘要：
自我对照病例系列（SCCS）研究设计越来越多地用于药物-药物相互作用（DDI）的药物流行病学研究，推断的目标是与伴随暴露于对象加沉淀剂药物与单独对象药物相关的发生率比（IRR）。虽然可以从分配索赔中推断出日常药物暴露，这些推论可能是不准确的，导致有偏见的内部收益率。研究人员经常使用宽限期(假设几天后持续的治疗影响)，但宽限期决定对暴露错误分类偏倚的影响尚不清楚.SCCS研究检查氯吡格雷（对象）和华法林（沉淀剂）之间的潜在DDI，我们使用模拟研究了由于沉淀剂或物体暴露错误分类引起的偏差。我们表明，错误分类的沉淀剂处理总是将估计的IRR偏向于零，而错误分类的对象处理可能会导致任一方向的偏差或没有偏差，取决于场景。Further,包括每个对象分配的宽限期可能会无意中增加错误分类偏差的风险。为了尽量减少这种偏见，我们建议1）在指定对象药物暴露发作时避免使用宽限期；2）包括每个沉淀剂暴露期之后的冲洗期。
