ORGANIZATION: The Fred Hutchinson Cancer Research Center PROBLEM OR ISSUE ADDRESSED: A key component of Comparative Effectiveness Research is the engagement of stakeholders in a collaborative process to identify research priorities.1 This research infrastructure is critical to building consensus around sufficient evidence thresholds and translating research into clinical practice. GOALS: Developing new information on the comparative effectiveness of medical technology will differ for emerging vs. established technologies.  We compare and contrast two large, federally-funded comparative effectiveness research (CER) projects: one to develop evidence for genomic technologies that are not yet in practice, and a second to generate evidence on imaging technologies that are widely used despite modest supporting evidence. OUTCOMES ITEMS USED IN THE DECISION: We characterized the composition of the two stakeholder groups and reviewed the test evaluation criteria to compare the distinct CER frameworks. A landscape-analysis of recent literature was used to identify potential studies, followed by feedback from pertinent experts to narrow the list of research topics. Test Target Profiles and Topic Briefs were then developed in both prioritization processes to identify top test candidates for further study. IMPLEMENTATION STRATEGY: Two CER frameworks, funded by the American Recovery and Reinvestment Act (ARRA) Grand Opportunities, are being used to identify research priorities for genomic applications for personalized medicine and for studies of cancer diagnostics. Both stakeholder engagement strategies employ an iterative process of conducting literature evaluation, soliciting stakeholder feedback and identifying top candidates for a prospective CER study. RESULTS: The ADVICE project (RC2CA148433-01) is focused on rapid turnaround CER studies in cancer diagnostics. This imaging study focuses on established MRI and PET-CT technologies used as part of staging for women with newly diagnosed breast cancer.  Since both are widely used for this indication, we convened a stakeholder group composed of community payers to engage in retrospective research of MRI and PET-CT use among women with breast cancer. The planned outcome of the retrospective evaluation is a locally-conducted prospective comparative effectiveness study of one or both imaging technologies, designed to consider feasibility as well as meeting evidence needs. The genomics project CANCERGEN (RC2 CA148570) developed an External Stakeholder Advisory Group with 3 constituents from each of the following stakeholder groups: 1) the life sciences industry, 2) federal agencies, 3) public/private payers, 4) medical professional organizations and 5) patient advocacy groups. Stakeholders will identify an emerging genomic application based on an iterative, priority-setting process that assesses CANCERGEN evaluation criteria. The final outcome of this project will be a prospective, controlled comparative effectiveness study of the top-ranked genomic test vs. current care, sponsored by the Southwest Oncology Group. Shared evaluation criteria between CANCERGEN and ADVICE included: economic impact, potential benefits, potential harms, trial feasibility and evidence of need. ADVICE criteria were based on Health Technology Assessment programs and the CANCERGEN Test Target Profiles.  ADVICE-specific domains included: 1) whether the topic was relevant to CER, 2) stakeholder/community interest, 3) existing practice guidelines and 4) diagnostic accuracy/efficacy.  Secondary criteria incorporated data on patient outcomes and payer factors, such as disease burden and the pressure of payers to cover the modality, respectively. A major barrier to both evaluation frameworks was the lack of evidence base for health applications that were selected by stakeholder groups as a high research priority. Coverage with Evidence Development (CED) emerged as a topic within both consortiums as a CER tool adopted by the Center for Medicare and Medicaid Services (CMS) for filling the evidence gaps in translational research.  In the CANCERGEN process this coverage mechanism was prompted by the researchers, in the ADVICE process the stakeholder group raised it as a funding strategy.  LESSONS LEARNED: A collaborative approach to evidence evaluation and prioritization was adopted by both stakeholder groups; however, the diversity of stakeholder perspectives in the CANCERGEN external stakeholder group required greater use of knowledge brokering between researchers and stakeholders to build consensus around evidentiary standards.2 Further methodology development should clarify the role of the researchers as knowledge brokering is transferred to a more stakeholder-driven prioritization process for assessing evidence needs. For both CER consortiums, CED was identified as a shared funding mechanism for translating health applications into evidence-based practice. Future development of stakeholder priority-setting processes will vary according to both the evidence needs of the convened stakeholder group and the data sources available for conducting CER studies. 1 Khoury MJ, Berg A, Coates R, Evans J, Teutsch SM, Bradley LA. The Evidence Dilemma in Genomic    Medicine. Health Affaris. 2008;27:1600-1611. 2 Khoury MJ. Dealing with the Evidence Dilemma in Genomics and Personalized Medicine. Clinical   Pharmacology and Therapeutics. 2010;87:635-638.