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Pragmatic RCTs nested within electronic health records (EHRs) can be useful to overcome such limitations. Serum lithium monitoring has often been underutilized in real-world practice in Japan. This trial aims to evaluate the effectiveness of the EHR-nested reminder system for serum lithium level monitoring in the maintenance of therapeutic lithium concentration and in the improvement of the quality of care for patients on lithium maintenance therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Kyoto Toyooka nested controlled trial of reminders (KONOTORI trial) is an EHR-nested, parallel-group, superiority, stratified, permuted block-randomized controlled trial. Screening, random allocation, reminder output, and outcome collection will be conducted automatically by the EHR-nested trial program. Patients with a mood disorder taking lithium carbonate for maintenance therapy will be randomly allocated to the two-step reminder system for serum lithium monitoring or to usual care. The primary outcome is the achievement of therapeutic serum lithium concentration between 0.4 and 1.0\u2009mEq\/L at 18\u2009months after informed consent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The KONOTORI trial uses EHRs to enable the efficient conduct of a pragmatic trial of the reminder system for lithium monitoring. This may contribute to improved quality of care for patients on lithium maintenance therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      University Hospital Medical Information Network (UMIN) Clinical Trials Registry,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/upload.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000037910\">UMIN000033633<\/jats:ext-link>\n                      . Registered on 3 July 2018.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-019-3847-9","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T09:07:10Z","timestamp":1576055230000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Electronic health record nested pragmatic randomized controlled trial of a reminder system for serum lithium level monitoring in patients with mood disorder: KONOTORI study protocol"],"prefix":"10.1186","volume":"20","author":[{"given":"Tomotsugu","family":"Seki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morio","family":"Aki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotsugu","family":"Kawashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomotaka","family":"Miki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2159-3776","authenticated-orcid":false,"given":"Toshi A.","family":"Furukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,11]]},"reference":[{"key":"3847_CR1","volume-title":"Large simple trials and knowledge generation in a learning health system: Workshop summary","author":"Institute of Medicine","year":"2013","unstructured":"Institute of Medicine. 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The trial has been approved by the Ethics Committee of the Kyoto University Graduate School of Medicine (registration number: C1401) and the Institutional Review Boards of Toyooka Hospital (registration number: 180).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"TS received a stipend from Pfizer, Inc.ST has received lecture fees from Boehringer Ingelheim, Astra-Zeneca, Taiho Pharmaceutical, Ono Pharmaceutical, and JMDC Inc. He received consultation fees from the Pharmaceuticals and Medical Devices Agency and DeNA Life Science and outsourcing fees from the Public Health Research Foundation. ST has received grants from the Japan Agency for Medical Research and Development, the Japanese Ministry of Health, Labor and Welfare, and the Japanese Ministry of Education, Culture, Sports, Science and Technology. He engaged in a research project of the Japan Agency for Medical Research and Development.KK received honoraria from Shin Nippon Biomedical Laboratories, Ltd.; research funds from Olympus Corporation, Sumitomo Dainippon Pharma Co., Ltd., Bayer Yakuhin Ltd., Stella.Pharma Corporation, Novartis Pharma K.K., CMIC Co., Ltd., Amgen Astellas BioPharma K.K., Suntory Beverage & Food Ltd., and Medical Platform Co., Ltd.; and holds stocks in School Health Record Center Co., Ltd. and Real World Data, Co., Ltd. There are no patent products under development or marketed products to declare that are relevant to those companies.TAF has received lecture fees from Janssen, Meiji, Mitsubishi-Tanabe, MSD,and Pfizer. TAF has received research support from Mitsubishi-Tanabe and Mochida.All other authors report that they have no relationships to disclose that are relevant to the contents of this paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"706"}}