Department of Medicine, University of Toronto, Toronto, Canada.
Evaluative Clinical Sciences Program, Sunnybrook Research Institute, Toronto, Canada.
J Gen Intern Med. 2023 Dec;38(16):3604-3609. doi: 10.1007/s11606-023-08395-x. Epub 2023 Oct 2.
Observational research can be strengthened by examining potential dose-response relationships that correlate a clinical intervention with a patient outcome. Despite being a classic criterion for establishing causality, dose-response testing can be difficult to interpret in clinical medicine due to multiple diverse pitfalls. This review introduces a cautionary framework for investigators considering dose-response relationships in observational research to support evidence-based medicine. Each pitfall is illustrated with a specific example relevant when analyzing a dose-response relationship. Several pitfalls stem from faulty interpretation including confounding by indication and fallible range selection. Additional pitfalls relate to improper analysis including fitting a nonlinear model and misclassification error. Further pitfalls arise in special situations including subjective self-report and artifacts from survival bias. These caveats are common sources of misunderstanding in analyses that examine the link between varying exposures and the intensity of clinical outcomes. Awareness of specific pitfalls, we suggest, might help advance the conduct, application, and translation of dose-response relationships in observational research to inform evidence-based medical care.
观察性研究可以通过检查临床干预与患者结局之间的潜在剂量-反应关系来加强。尽管剂量-反应检验是确定因果关系的经典标准，但由于存在多种不同的陷阱，在临床医学中解释起来可能具有一定难度。本综述为考虑在观察性研究中建立剂量-反应关系的研究人员引入了一个警示框架，以支持循证医学。每个陷阱都通过在分析剂量-反应关系时相关的具体示例来说明。一些陷阱源于错误的解释，包括混杂因素和错误的范围选择。其他陷阱与不当分析有关，包括拟合非线性模型和分类错误。在特殊情况下还会出现其他陷阱，包括主观的自我报告和生存偏差的影响。这些注意事项是分析中常见的误解来源，这些分析检查了不同暴露与临床结局强度之间的联系。我们建议，了解特定的陷阱可能有助于促进观察性研究中剂量-反应关系的开展、应用和转化，以为循证医疗提供信息。
