Breaking Down Bias: A Methodological Primer on Identifying, Evaluating, and Mitigating Bias in Cardiovascular Research

Systematic error, often referred to as bias is an inherent challenge in observational cardiovascular research, and has the potential to profoundly influence the design, conduct, and interpretation of study results. If not carefully considered and managed, bias can lead to spurious results, which can misinform clinical practice or public health initiatives and compromise patient outcomes. This methodological primer offers a concise introduction to identifying, evaluating, and mitigating bias in observational cardiovascular research studies that examine the causal association between an exposure (or treatment) and an outcome. Using high-profile examples from the cardiovascular literature, this review provides a theoretical overview of 3 main types of bias—selection bias, information bias, and confounding—and discusses the implications of specialized types of biases commonly encountered in longitudinal cardiovascular research studies, namely, competing risks, immortal time bias, and confounding by indication. Furthermore, strategies and tools that can be used to minimize and assess the influence of bias are highlighted, with a specific focus on using the target trial framework, directed acyclic graphs, quantitative bias analysis, and formal risk of bias assessments. This review aims to assist researchers and health care professionals in designing observational studies and selecting appropriate methodologies to reduce bias, ultimately enhancing the estimation of causal associations in cardiovascular research.