Project Summary: Engagement Optimization Unit The overall goal of the EOU of the Washington University Participant Engagement and Cancer Genomic Sequencing Center (WU-PE-CGS) is to conduct ongoing and iterative research to integrate optimal approaches to participant engagement in the recruitment, consent, follow-up, and communication of genomic characterization results. The EOU will optimize the engagement process for genomic characterization of patients diagnosed with three rare cancers or cancers that require more research, including those that significantly impact populations (e.g., rural) that require more research on cholangiocarcinoma, multiple myeloma, and early onset colorectal cancer. The outcomes of research conducted within the EOU will be fully integrated with the Participant Engagement Unit (PEU) and Genome Characterization Unit (GCU) to optimize participant experiences throughout the genomic research process. The EOU will support the overall mission of WU-PE-CGS through the following aims: (1) conduct ongoing evaluation of participant engagement and ELSI concerns related to genomic testing among low-resourced populations with rare cancers; (2) conduct a randomized controlled trial to optimize the return of results process; (3) use an embedded ethics approach to synthesize and address ELSI issues arising across all units and the Patient Engagement Advisory Board to optimize participant engagement. The EOU will use an implementation science framework for the main research objectives. Aim 1 will interview a random sample of participants at various stages in their study participation (decliners, post-consent, post-disclosure). Aim 2 will expand and test a web-based decision aid to elicit participants’ values and preferences for receiving results from cancer genomic sequencing. Participants will be randomized to intervention (Genomics ADvISOR decision aid) or control (standard discussion). In Aim 3, we will use embedded ethics to explore ELSI concerns that arise when genetic testing is offered to low-resourced (e.g., rural-residing) adults with rare cancer. This approach will ensure that ethical issues arising within components (PEU, EOU, and GCU) will be identified and communicated across the entire center. The innovation of this project brings rigorous implementation science to the otherwise slow diffusion of guideline-driven genetic testing and return of results to cancer patients. We will focus our engagement optimization research on rural and high-risk low-resourced populations that require more research in cancer genomic analyses and have often been omitted from implementation science-directed studies in the area of genomic medicine.