Bias in Large Language Models Across Clinical Applications: A Systematic Review

Background: Large language models (LLMs) are rapidly being integrated into healthcare, promising to enhance various clinical tasks. However, concerns exist regarding their potential for bias, which could compromise patient care and exacerbate health inequities. This systematic review investigates the prevalence, sources, manifestations, and clinical implications of bias in LLMs. Methods: We conducted a systematic search of PubMed, OVID, and EMBASE from database inception through 2025, for studies evaluating bias in LLMs applied to clinical tasks. We extracted data on LLM type, bias source, bias manifestation, affected attributes, clinical task, evaluation methods, and outcomes. Risk of bias was assessed using a modified ROBINS-I tool. Results: Thirty-eight studies met inclusion criteria, revealing pervasive bias across various LLMs and clinical applications. Both data-related bias (from biased training data) and model-related bias (from model training) were significant contributors. Biases manifested as: allocative harm (e.g., differential treatment recommendations); representational harm (e.g., stereotypical associations, biased image generation); and performance disparities (e.g., variable output quality). These biases affected multiple attributes, most frequently race/ethnicity and gender, but also age, disability, and language. Conclusions: Bias in clinical LLMs is a pervasive and systemic issue, with a potential to lead to misdiagnosis and inappropriate treatment, particularly for marginalized patient populations. Rigorous evaluation of the model is crucial. Furthermore, the development and implementation of effective mitigation strategies, coupled with continuous monitoring in real-world clinical settings, are essential to ensure the safe, equitable, and trustworthy deployment of LLMs in healthcare.