《药物流行病学研究方法学指南（第2版）》及其系列解读（12）：阴性对照方法的应用与案例解读

打开文本图片集

【关键词】药物流行病学；方法学；指南；阴性对照；未测量偏倚【中图分类号】 【文献标识码】A

【Abstract】 Unmeasured confounding is a common challenge in pharmacoepidemiological studies. Negative controls can be used to detect potential unmeasured confounding and thereby validate the reliability of study.Based on the Guidelines for Pharmacoepidemiological Research Methodology （2nd edition），this study systematically interprets theapplication of the negative control methods and related case studies.First， the definitionand main types of negativecontrols are introduced，including negative exposure control， negative period control，and negative outcome control，clarifying their basic concepts and applicable scenarios.Second， it elaborates the primary purpose of this method，which is to identifyand adjust for unmeasured confounding. Then，the implementation steps and statistical analysis methods are outlined，covering selection criteria during the study design phase and bias detection strategies during the statistical analysis phase.Finally， through detailed analysis of four types of typical cases，the practical application value of negative controls is demonstrated in areas such as verifying drug safety， evaluating effctiveness，and identifying and adjusting for unmeasured confounding. The study emphasizes that while negative controls may not eliminate bias，they serve as a supplementary analytical tool， when combined with other epidemiological methods，can effectively enhance thequalityof causal inference in observational studies.This research provides methodological references for the appropriate selection and application of negative controls in pharmacoepidemiological practice，thereby contributing to the advancement of high-quality researches.

【KeyWords】Pharmacoepidemiology; Methodology; Guidelines; Negative controls; Unmeasurec confounding

药物流行病学主要研究药物在人群中的使用情况、有效性及安全性，旨在评估其获益与风险，为临床实践和公共卫生政策提供关键证据[-2]方法学指南对于规范该学科发展具有重要作用。（剩余18182字）