Digital twins in increasing diversity in clinical trials: A systematic review

The integration of digital twin (DT) technology and artificial intelligence (AI) into clinical trials holds transformative potential for addressing persistent inequities in participant representation. This systematic review evaluates the role of these technologies in improving diversity, particularly in racial, ethnic, gender, age, and socioeconomic dimensions, minimizing bias, and allowing personalized medicine in clinical research settings. Evidence from 90 studies reveals that digital twins offer dynamic simulation capabilities for trial design, while AI facilitates predictive analytics and recruitment optimization. However, implementation remains hindered by fragmented regulatory frameworks, biased datasets, and infrastructural disparities. Ethical concerns,including privacy, consent, and algorithmic opacity, further complicate the deployment. Inclusive data practices identified in the literature include the use of demographically representative training data, participatory data collection frameworks, and equity audits to detect and correct systemic bias. Fairness in AI and DT models is primarily operationalized through group fairness metrics such as demographic parity and equalized odds, along with fairness, aware model training and validation. Key gaps include the lack of global standards, underrepresentation in model training, and challenges in real-world adoption. To overcome these barriers, the review proposes actionable directions: developing inclusive data practices, harmonizing regulatory oversight, and embedding fairness into computational model design. By focusing on diversity as a design principle, AI and DT technologies can support a more equitable and generalizable future for clinical research.