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Using the LHS framework, we describe current VA research initiatives in mental health and substance use disorders that rigorously evaluate national programs and policies designed to reduce the risk of suicide and opioid use disorder (data to knowledge); test implementation strategies to improve the spread of effective programs for Veterans at risk of suicide or opioid use disorder (knowledge to performance); and identify novel research directions in suicide prevention and opioid\/pain treatments emanating from implementation and quality improvement research (performance to data). Lessons learned are encapsulated into best practices for building and sustaining an LHS within health systems, including the need for early engagement with clinical leaders; pragmatic research questions that focus on continuous improvement; multi\u2010level, ongoing input from regional and local stakeholders, and business case analyses to inform ongoing investment in sustainable infrastructure to maintain the research\u2010health system partnership. Essential ingredients for supporting VA as an LHS include data and information sharing capacity, protected time for researchers and leaders, and governance structures to enhance health system ownership of research findings. For researchers, incentives to work with health systems operations (e.g., retainer funding) are vital for LHS research to be recognized and valued by academic promotion committees.<\/jats:p>","DOI":"10.1096\/fba.2020-00124","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T09:21:20Z","timestamp":1616404880000},"page":"626-638","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Learning health systems: Driving real\u2010world impact in mental health and substance use disorder research"],"prefix":"10.1096","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5815-6401","authenticated-orcid":false,"given":"Amy M.","family":"Kilbourne","sequence":"first","affiliation":[{"name":"Health Services Research and Development Office of Research and Development Veterans Health Administration U.S. Department of Veterans Affairs Washington DC USA"},{"name":"Department of Learning Health Sciences University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Evans","sequence":"additional","affiliation":[{"name":"Health Services Research and Development Office of Research and Development Veterans Health Administration U.S. Department of Veterans Affairs Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Atkins","sequence":"additional","affiliation":[{"name":"Health Services Research and Development Office of Research and Development Veterans Health Administration U.S. Department of Veterans Affairs Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Crossing the Quality Chasm: A New Health System for the 21st Century","author":"Institute of Medicine","year":"2001"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1637943"},{"key":"e_1_2_12_4_1","volume-title":"Future of Health Services Research","author":"National Academy of Medicine","year":"2018"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2012.11111616"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2009.07.008"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60648-6"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.62.6.593"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.23.3095"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.129"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2008.540"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.156.1.5"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-020-06143-z"},{"key":"e_1_2_12_14_1","volume-title":"Best Care at a Lower Cost: the Path to Continuously Learning Health Care in America","author":"Institute of Medicine","year":"2013"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1108\/JHOM-08-2013-0164"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-020-05865-4"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1017\/cts.2020.25"},{"key":"e_1_2_12_18_1","volume-title":"Veterans Health administration. 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