{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T10:14:17Z","timestamp":1771841657165,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T00:00:00Z","timestamp":1563148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T00:00:00Z","timestamp":1563148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HB16C0075"],"award-info":[{"award-number":["HB16C0075"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s13063-019-3537-7","type":"journal-article","created":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T14:08:54Z","timestamp":1563199734000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Safety, effectiveness, and economic evaluation of an herbal medicine, Ukgansangajinpibanha granule, in children with autism spectrum disorder: a study protocol for a prospective, multicenter, randomized, double-blinded, placebo-controlled, parallel-group clinical trial"],"prefix":"10.1186","volume":"20","author":[{"given":"Sun Haeng","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seungwon","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-hun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Min","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Yoon","family":"Do","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sulgi","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boram","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Jin","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Yong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2465-3298","authenticated-orcid":false,"given":"Gyu Tae","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,7,15]]},"reference":[{"key":"3537_CR1","volume-title":"Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition","author":"American Psychiatric Association","year":"2015","unstructured":"American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Seoul: Hakjisa; 2015."},{"key":"3537_CR2","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1203\/PDR.0b013e31819e7203","volume":"65","author":"E Fombonne","year":"2009","unstructured":"Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009;65:591\u20138.","journal-title":"Pediatr Res"},{"key":"3537_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/DBP.0000000000000235","volume":"37","author":"DL Christensen","year":"2016","unstructured":"Christensen DL, Bilder DA, Zahorodny W, Pettygrove S, Durkin MS, Fitzgerald RT, et al. Prevalence and characteristics of autism spectrum disorder among 4-year-old children in the autism and developmental disabilities monitoring network. J Dev Behav Pediatrics. 2016;37:1\u20138.","journal-title":"J Dev Behav Pediatrics"},{"key":"3537_CR4","volume-title":"Assessment, diagnosis and interventions for autism spectrum disorders","author":"Scottish Intercollegiate Guidelines Network (SIGN)","year":"2016","unstructured":"Scottish Intercollegiate Guidelines Network (SIGN). Assessment, diagnosis and interventions for autism spectrum disorders. Edinburgh: SIGN; 2016."},{"key":"3537_CR5","volume-title":"Pediatrics of Korean Medicine. revised edn","author":"Textbook Compiliation Committee","year":"2015","unstructured":"Textbook Compiliation Committee. Pediatrics of Korean Medicine. revised edn. Seoul: Euisungdang; 2015."},{"key":"3537_CR6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.13048\/jkm.18021","volume":"39","author":"KH Cho","year":"2018","unstructured":"Cho KH, Kim TH, Jin C, Lee JE, Kwon S. The literary trends of herbal prescription Ukgan-san and its application in modern traditional Korean medicine. J Korean Med. 2018;39:17\u201327.","journal-title":"J Korean Med"},{"key":"3537_CR7","doi-asserted-by":"publisher","first-page":"551","DOI":"10.2174\/1871527315666160413120541","volume":"15","author":"R Wake","year":"2016","unstructured":"Wake R, Miyaoka T, Furuya M, Hashioka S, Horiguchi J. Effects of Yokukansan, a Japanese Kampo Medicine for Symptoms Associated Autism Spectrum Disorder. CNS Neurol Disord Drug Targets. 2016;15:551\u201363.","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"3537_CR8","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/s12311-014-0611-2","volume":"14","author":"K Muneoka","year":"2015","unstructured":"Muneoka K, Kuwagata M, Ogawa T, Shioda S. Mother\/offspring co-administration of the traditional herbal remedy yokukansan during the nursing period influences grooming and cerebellar serotonin levels in a rat model of neurodevelopmental disorders. Cerebellum. 2015;14:86\u201396.","journal-title":"Cerebellum"},{"key":"3537_CR9","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s12906-017-1710-7","volume":"17","author":"H Fujiwara","year":"2017","unstructured":"Fujiwara H, Han Y, Ebihara K, Awale S, Araki R, Yabe T, et al. Daily administration of yokukansan and keishito prevents social isolation-induced behavioral abnormalities and down-regulation of phosphorylation of neuroplasticity-related signaling molecules in mice. BMC Complement Altern Med. 2017;17:195.","journal-title":"BMC Complement Altern Med"},{"key":"3537_CR10","first-page":"693","volume":"20","author":"R Sato","year":"2002","unstructured":"Sato R, Kato K, Yamada K, Akama F, Kimoto K, Kimoto K, et al. A case of irritability with autistic disorder in children and adolescents improved by Yokukansan. Psychiatr. 2002;20:693\u20138.","journal-title":"Psychiatr"},{"key":"3537_CR11","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1089\/cap.2012.0108","volume":"23","author":"R Wake","year":"2013","unstructured":"Wake R, Miyaoka T, Inagaki T, Furuya M, Ieda M, Liaury K, et al. Yokukansan (TJ-54) for irritability associated with pervasive developmental disorder in children and adolescents: a 12-week prospective, open-label study. J Child Adolesc Psychopharmacol. 2013;23:329\u201336.","journal-title":"J Child Adolesc Psychopharmacol"},{"key":"3537_CR12","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/1471-244X-12-215","volume":"12","author":"T Miyaoka","year":"2012","unstructured":"Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, et al. Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger\u2019s disorder: a 12-week prospective, open-label study. BMC Psychiatry. 2012;12:215.","journal-title":"BMC Psychiatry"},{"key":"3537_CR13","volume-title":"Handbook of Kampo treatment for children","author":"Japanese Pediatric Oriental Medicine Association","year":"2015","unstructured":"Japanese Pediatric Oriental Medicine Association. Handbook of Kampo treatment for children. Tokyo: Japan Pediatric Medical Publishers; 2015."},{"key":"3537_CR14","unstructured":"KIPC DRUG INFO. [\n                    http:\/\/www.health.kr\/searchDrug\/result_drug.asp?drug_cd=2014091600004\n                    \n                  ]. Accessed 31 July 2018."},{"key":"3537_CR15","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1542\/peds.2013-3995","volume":"133","author":"BO McElhanon","year":"2014","unstructured":"McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014;133:872\u201383.","journal-title":"Pediatrics"},{"key":"3537_CR16","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1590\/1516-3180.2017.0058200317","volume":"135","author":"L Lyra","year":"2017","unstructured":"Lyra L, Rizzo LE, Sunahara CS, Pachito DV, Latorraca COC, et al. What do Cochrane systematic reviews say about interventions for autism spectrum disorders? Sao Paulo Med J. 2017;135:192\u2013201.","journal-title":"Sao Paulo Med J"},{"key":"3537_CR17","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.jams.2017.09.001","volume":"10","author":"HMM Abo Almaali","year":"2017","unstructured":"Abo Almaali HMM, Gelewkhan A, Mahdi ZAA. Analysis of Evidence-Based Autism Symptoms Enhancement by Acupuncture. J Acupunct Meridian Stud. 2017;10:375\u201384.","journal-title":"J Acupunct Meridian Stud"},{"key":"3537_CR18","first-page":"1057539","volume":"2018","author":"B Lee","year":"2018","unstructured":"Lee B, Lee J, Cheon JH, Sung HK, Cho SH, Chang GT. The Efficacy and Safety of Acupuncture for the Treatment of Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2018;2018:1057539.","journal-title":"Evid Based Complement Alternat Med"},{"key":"3537_CR19","doi-asserted-by":"publisher","first-page":"e14880","DOI":"10.1097\/MD.0000000000014880","volume":"98","author":"C Liu","year":"2019","unstructured":"Liu C, Li T, Wang Z, Zhou R, Zhuang L. Scalp acupuncture treatment for children's autism spectrum disorders: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98:e14880.","journal-title":"Medicine (Baltimore)"},{"key":"3537_CR20","first-page":"1","volume":"17","author":"MS Shin","year":"1998","unstructured":"Shin MS, Kim YH. Standardization study for the Korean version of Childhood Autism Rating Scale: reliability, validity and cut-off score. Korean J Clin Psychol. 1998;17:1\u201315.","journal-title":"Korean J Clin Psychol"},{"key":"3537_CR21","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/j.1469-7610.1980.tb01797.x","volume":"21","author":"DA Krug","year":"1980","unstructured":"Krug DA, Arick J, Almond P. Behavior checklist for identifying severely handicapped individuals with high levels of autistic behavior. J Child Psychol Psychiatry. 1980;21:221\u20139.","journal-title":"J Child Psychol Psychiatry"},{"key":"3537_CR22","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/pits.20122","volume":"43","author":"RC Eaves","year":"2006","unstructured":"Eaves RC, Williams TO. The reliability and construct validity of ratings for the autism behavior checklist. Psychol Sch. 2006;43:129\u201342.","journal-title":"Psychol Sch"},{"key":"3537_CR23","first-page":"1183","volume":"120","author":"CP Johnson","year":"2007","unstructured":"Johnson CP, Myers SM, American Academy of Pediatrics Council on Children With Disabilities. Identification and evaluation of children with autism spectrum disorders. Am Acad Pediatrics Counc Children Disabil. 2007;120:1183\u2013215.","journal-title":"Am Acad Pediatrics Counc Children Disabil"},{"key":"3537_CR24","first-page":"144","volume":"10","author":"N Yousefi","year":"2015","unstructured":"Yousefi N, Dadgar H, Mohammadi MR, Jalilevand N, Keyhani MR, Mehri A. The Validity and Reliability of Autism Behavior Checklist in Iran. Iran J Psychiatry. 2015;10:144\u20139.","journal-title":"Iran J Psychiatry"},{"key":"3537_CR25","first-page":"492","volume":"89","author":"MG Aman","year":"1985","unstructured":"Aman MG, Singh NN, Stewart AW, Field CJ. Psychometric characteristics of the aberrant behavior checklist. Am J Ment Defic. 1985;89:492\u2013502.","journal-title":"Am J Ment Defic"},{"key":"3537_CR26","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s10803-012-1689-3","volume":"43","author":"L Scahill","year":"2013","unstructured":"Scahill L, Hallett V, Aman MG, McDougle CJ, Eugene Arnold L, McCracken JT, et al. Brief Report: social disability in autism spectrum disorder: results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network trials. J Autism Dev Disord. 2013;43:739\u201346.","journal-title":"J Autism Dev Disord"},{"key":"3537_CR27","first-page":"237","volume":"92","author":"MG Aman","year":"1987","unstructured":"Aman MG, Singh NN, Turbott SH. Reliability of the Aberrant Behavior Checklist and the effect of variations in instructions. Am J Ment Defic. 1987;92:237\u201340.","journal-title":"Am J Ment Defic"},{"key":"3537_CR28","volume-title":"Social Maturity Scale Protocol","author":"SG Kim","year":"1995","unstructured":"Kim SG, Kim OG. Social Maturity Scale Protocol. Seoul: Jungang Aptitude Laboratory; 1995."},{"key":"3537_CR29","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S0895-4356(01)00411-5","volume":"55","author":"H Raat","year":"2002","unstructured":"Raat H, Bonsel GJ, Essink-Bot ML, Landgraf JM, Gemke RJ. Reliability and validity of comprehensive health status measures in children: The Child Health Questionnaire in relation to the Health Utilities Index. J Clin Epidemiol. 2002;55:67\u201376.","journal-title":"J Clin Epidemiol"},{"key":"3537_CR30","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1007\/s11136-010-9649-x","volume":"19","author":"U Ravens-Sieberer","year":"2010","unstructured":"Ravens-Sieberer U, Wille N, Badia X, Bonsel G, Burstr\u00f6m K, et al. Feasibility, reliability, and validity of the EQ-5D-Y: results from a multinational study. Qual Life Res. 2010;19:887\u201397.","journal-title":"Qual Life Res"},{"key":"3537_CR31","volume-title":"Guide to Korean Parenting Stress Index","author":"RR Abidin","year":"2008","unstructured":"Abidin RR, Jung GM, Lee GS, Park JA. Guide to Korean Parenting Stress Index. Seoul: Insight of Psychology; 2008."},{"key":"3537_CR32","unstructured":"Zhou NY, Li YC, Jiang XY. Clinical Observation of Supplemented Lizhong Decoction in Treating Children Autism. J New Chinese Med. 2015;47(6):200\u20132."},{"key":"3537_CR33","first-page":"2105","volume":"43","author":"YB Sun","year":"2016","unstructured":"Sun YB, Song HJ, Feng TZ, Yuan Y, Zhao NX. Comprehensive treatment of 60 cases of childhood autism. Liaoning J Tradit Chin Med. 2016;43:2105\u20138.","journal-title":"Liaoning J Tradit Chin Med"},{"key":"3537_CR34","doi-asserted-by":"publisher","first-page":"8614680","DOI":"10.1155\/2017\/8614680","volume":"2017","author":"M Bang","year":"2017","unstructured":"Bang M, Lee SH, Cho SH, Yu SA, Kim K, Lu HY, et al. Herbal Medicine Treatment for Children with Autism Spectrum Disorder: A Systematic Review. Evid Based Complement Alternat Med. 2017;2017:8614680.","journal-title":"Evid Based Complement Alternat Med"},{"key":"3537_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss6503a1","volume":"65","author":"DL Christensen","year":"2016","unstructured":"Christensen DL, Baio J, Van Naarden Braun K, Bilder D, Charles J, Constantino JN, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. MMWR Surveill Summ. 2016;65:1\u201323.","journal-title":"MMWR Surveill Summ"},{"key":"3537_CR36","volume-title":"2019 Spring Conference and Workshop","author":"SH Shin","year":"2019","unstructured":"Shin SH. Understanding of high-functioning autism spectrum disorder. In: 2019 Spring Conference and Workshop. Seoul: Korean Association for Persons with Autism, Korean Academy for Autism Spectrim Disorder; 2019."},{"key":"3537_CR37","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1538\/expanim.16-0028","volume":"65","author":"H Tamano","year":"2016","unstructured":"Tamano H, Yusuke E, Ide K, Takeda A. Influences of yokukansankachimpihange on aggressive behavior of zinc-deficient mice and actions of the ingredients on excessive neural exocytosis in the hippocampus of zinc-deficient rats. Exp Anim. 2016;65:353\u201361.","journal-title":"Exp Anim"},{"key":"3537_CR38","doi-asserted-by":"publisher","first-page":"10014","DOI":"10.3390\/molecules180810014","volume":"18","author":"A Ito","year":"2013","unstructured":"Ito A, Shin N, Tsuchida T, Okubo T, Norimoto H. Antianxiety-like effects of Chimpi (dried citrus peels) in the elevated open-platform test. Molecules. 2013;18:10014\u201323.","journal-title":"Molecules"},{"key":"3537_CR39","doi-asserted-by":"publisher","first-page":"14959","DOI":"10.3390\/molecules200814959","volume":"20","author":"C Murayama","year":"2015","unstructured":"Murayama C, Watanabe S, Nakamura M, Norimoto H. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons. Molecules. 2015;20:14959\u201369.","journal-title":"Molecules"},{"key":"3537_CR40","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1046\/j.1440-1819.2002.01006.x","volume":"56","author":"R Aizawa","year":"2002","unstructured":"Aizawa R, Kanbayashi T, Saito Y, Ogawa Y, Sugiyama T, Kitajima T, et al. Effects of Yoku-kan-san-ka-chimpi-hange on the sleep of normal healthy adult subjects. Psychiatry Clin Neurosci. 2002;56:303\u20134.","journal-title":"Psychiatry Clin Neurosci."},{"key":"3537_CR41","first-page":"49","volume":"31","author":"HJ Shin","year":"2017","unstructured":"Shin HJ, Lee B, Lee J, Chang GT. A clinical study of treating autism spectrum disorder in childhood. J Pediatr Korean Med. 2017;31:49\u201360.","journal-title":"J Pediatr Korean Med"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-019-3537-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-019-3537-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-019-3537-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T23:23:38Z","timestamp":1594682618000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-019-3537-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,15]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["3537"],"URL":"https:\/\/doi.org\/10.1186\/s13063-019-3537-7","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,15]]},"assertion":[{"value":"14 August 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The trial protocol has been approved by the Ministry of Food and Drug Safety (#31635) and the institutional review board at Kyung Hee University Korean Medicine Hospital at Gangdong (KHNMCOH 2017\u201308-008) and Kyung Hee University Korean Medicine Hospital (KOMCIRB 2017\u201310-041).","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":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"434"}}