Background: Conventional recommendations in national prevention guidelines often fail to address differences in outcome risk and life expectancy across the target population. By ignoring such differences, conventional recommendations can inadvertently lead to substantial underuse (by excluding Veterans with potentially high net benefit who do not meet a conventional cutoff) and overuse (by including Veterans for whom net benefit would be limited). Further, minoritized patients who could most benefit from prevention are often disproportionately excluded by conventional recommendations, exacerbating racial disparities. The long- term goal of the proposed research is to support optimal preventive care decisions for all Veterans. The overall objective of this proposal is to study an alternative guideline approach (“tailored” recommendations based on multivariable prediction) that can better support individualized prevention efforts. A second goal is to study the extent to which optimizing decisions for individuals can broaden the public health impact of preventive care programs within VA. We use lung cancer screening, statin use, and blood pressure treatment as case studies as they are ideal models for studying the key issues. Significance: This work is significant because current knowledge gaps in guideline development, which we address in this proposal, inhibit progress toward more nuanced preventive care recommendations that often better identify high-benefit patients and enable more Veteran-centered care. Innovation and Impact: The proposed research is innovative because it will advance a different paradigm for developing preventive care guidelines both within and outside VA, which will open new horizons for optimizing the delivery of cancer screening, cardiovascular prevention, and other prevention. The rationale underlying the proposed work is that its successful completion would enable guideline-level assessment of when tailored recommendations would be highly advantageous, to promote more effective and personalized care and reduce racial disparities. Specific Aims: Aim 1: Estimate “individualized” net benefit for lung cancer screening, statin use, and blood pressure treatment. Aim 2: Estimate the comparative effects of conventional recommendations vs. tailored recommendations. Aim 3: Identify best practices for examining tailored recommendations in future guidelines. Methods: Under Aim 1, we will adapt existing microsimulation models for each preventive service to estimate the distribution of predicted (“individualized”) net benefit across the target Veteran population. This will inform the development of tailored recommendations under the guidance of the Aim 3 Expert Panel. Then, in Aim 2, we will use Aim 1 microsimulation evidence to examine the pros and cons of conventional vs. tailored approaches, again with close input from the Expert Panel. For Aim 3a, an Expert Advisory Panel of guideline experts will engage in a longitudinal process t...