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Searching the Clinical Fitness Landscape 1 2,4 3,4 5 Margaret J. Eppstein *, Jeffrey D. Horbar , Jeffrey S. Buzas , Stuart A. Kauffman 1 Department of Computer Science, University of Vermont, Burlington, Vermont, United States of America, 2 Department of Pediatrics, University of Vermont, Burlington, Vermont, United States of America, 3 Department of Mathematics Statistics, University of Vermont, Burlington, Vermont, United States of America, 4 Vermont Oxford Network, Burlington, Vermont, United States of America, 5 Complex Systems Center, University of Vermont, Burlington, Vermont, United States of America Abstract Widespread unexplained variations in clinical practices and patient outcomes suggest major opportunities for improving the quality and safety of medical care. However, there is little consensus regarding how to best identify and disseminate healthcare improvements and a dearth of theory to guide the debate. Many consider multicenter randomized controlled trials to be the gold standard of evidence-based medicine, although results are often inconclusive or may not be generally applicable due to differences in the contexts within which care is provided. Increasingly, others advocate the use ‘‘quality improvement collaboratives’’, in which multi-institutional teams share information to identify potentially better practices that are subsequently evaluated in the local contexts of specific institutions, but there is concern that such collaborative learning approaches lack the statistical rigor of randomized trials. Using an agent-based model, we show how and why a collaborative learning approach almost invariably leads to greater improvements in expected patient outcomes than more traditional approaches in searching simulated cl