PROJECT SUMMARY. Prescribing cascades (PCs), in which drug-induced adverse events (AEs) result in additional treatment rather than deprescribing or dose reduction of the offending agent, are a central problem in geriatric polypharmacy. Unlike other drug combinations that should be avoided, such as drug-drug interactions, there is currently no process that alerts providers of PCs. To prevent or deprescribe PCs, providers must evaluate complex medication regimens and multiple chronic conditions that may contribute to drug-induced AEs. Appropriate design and implementation of clinical decision support (CDS) offers a promising approach to enhance timely detection of PCs. In this work, I will use a research framework that evaluates PCs and develops CDS tools for detection in clinical practice, using the example of a presumably common and problematic PC: calcium channel blocker-associated lower extremity edema leading to the prescribing of a loop diuretic (CCBLEELoop). My specific aims include (Aim 1) estimating the incidence and evaluating which populations are at highest risk of CCBLEELoop PC, (Aim 2) quantifying excess AEs, healthcare utilization, and costs associated with the CCBLEELoop PC, and (Aim 3) developing and validating a CCBLEELoop PC algorithm for use in CDS to prospectively identify individuals with the PC. This NIA K08 proposal will lay the foundation, both in training and research output, for building an independent research program that combats polypharmacy in older adults, with particular focus on minimizing unnecessary medication use. My extensive experience in geriatric clinical pharmacy and my role as the Assistant Director of Pharmacy Services with University of Florida (UF) Health Physicians, the faculty practice of UF Health, will ensure deep clinical context and relevance of this work. My initial exposure to observational research methods and experience with Medicare data during my doctoral training will be enhanced through this K award in three distinct areas relevant to the proposed work: (1) pharmacoepidemiologic methods including the use of advanced longitudinal analyses to make causal inferences on drug effects, (2) development and validation of CDS, and (3) implementation science. UF Health is the largest fully-integrated academic health center in the Southeast and its excellent big data infrastructure provides an ideal environment for achieving the proposed objectives and my long-term goals. Dr. Winterstein will guide my training in pharmacoepidemiology and lead a multidisciplinary mentorship team composed of experts in CDS development and implementation and economic evaluation of drug effects (Dr. Malone), aging (Dr. Manini), biostatistics (Dr. Brumback), clinical management of hypertension (Dr. Pepine), clinical geriatrics (Dr. Solberg), and alert development, evaluation, and implementation (Dr. Staley). The integrated mentored research experience and training will allow me to compete for R01 funding focused o...