Title: Enhancing the Diversity of Participants in the WISDOM Clinical Trial: Practical Challenges and Ethical Implications. Abstract This bioethics supplement request expands the work of our NCI-funded R01 Expanding the WISDOM Study’s Diversity, Reach, and Generalizability. WISDOM (Women Informed to Screen Depending on Measures of Risk) is a pragmatic trial comparing a risk-based approach to breast cancer screening—in which the frequency and modality of screening is dependent on a personalized risk calculation—against the gold standard of annual screening. The goal is to determine whether a personalized approach is as safe, less morbid, better accepted by women, encourages uptake of preventive interventions, and is of higher health care value (better outcomes at less cost psychologically, physically, and financially). The purpose of the parent grant (which sponsors the supplement) is to increase enrollment and enhance the diversity of the WISDOM study population in order to increase generalizability to the US population. The proposed supplement builds upon a unique interdisciplinary partnership between the WISDOM clinical trial team and a team of ELSI investigators funded by a separate NCI R01 to study the social and ethical implications of WISDOM, titled: Precision Genomics in the WISDOM Pragmatic Clinical Trial: An “Embedded" ELSI Study of Risk-based Breast Cancer Screening. This project uses empirical and normative bioethics methods to identify and analyze the ELSI (ethical, legal, and social implications) challenges of risk-based screening. The embedded ethics project is guided by an overarching objective: to understand the intersection of precision genomics screening with known cancer health disparities. The proposed bioethics supplement will facilitate and expand research on the ELSI issues that arise as the WISDOM trial continues to innovate and evolve in order to meet its recruitment and retention goals and its commitment to enhance inclusion of diverse populations. The new aims proposed for the supplement will expand upon this unique opportunity and will address critical emerging issues not included in our original study design. Our Specific Aims are: (1) To expand the Ethics Working Group to include representatives from WISDOM’s four new enhanced-diversity recruitment sites and to extend the Ethics Working Group through 2022, allowing the group to continue to offer advice to WISDOM stakeholders in real time; and (2) To elucidate the challenges of enrolling racially and ethnically diverse participants in the WISDOM trial by interviewing study decliners across the original clinical study sites along with newly added clinical sites selected to enhance diversity. The proposed supplement is significant because little is known about recruitment of diverse populations in fully online studies. WISDOM’s efforts to enhance diversity while maintaining a largely online approach to recruitment requires study. This research with decliners will not on...