{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:43:12Z","timestamp":1762324992703,"version":"3.37.3"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973694"],"award-info":[{"award-number":["81973694"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2021,4,21]]},"abstract":"<jats:p>Background. Multiple primary outcomes are commonly used in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM). Analysis and interpretation of the results of CHM RCTs with many outcomes are not clear. No previous studies have systematically assessed the use of multiple primary outcomes in this area. This study aimed to assess the reporting of multiple primary outcomes and the statistical methods used to adjust multiplicity in RCTs of CHM. Methods. Search for RCTs of CHM published in English between January 2010 and December 2019 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was undertaken. We randomly selected 20% of the included RCTs as the analyzing sample of this study. The number of multiple primary outcomes, the methods used to adjust the multiplicity in statistical analysis and sample size estimate, and the trial information were collected. For RCTs that adopted multiple primary outcomes without the multiplicity adjustment, we used Bonferroni correction to adjust. Results. 227 CHM RCTs were included in our study. 92 (40.5%) failed to report what their primary outcome was. Of 135 (59.5%) RCTs that reported primary outcome, 93 (68.9%) reported one and 42 (31.1%) reported more than one primary outcome (range 2\u20135). Of 42 RCTs that reported multiple primary outcomes, only 5 adjusted for multiple outcomes. If multiplicity had been accounted for using Bonferroni correction, 10 (37.0%) RCTs that reported a significant result had demonstrated a nonsignificant result, giving the adjusted P value. Only one of the 42 RCTs calculated sample size based on multiple primary outcomes. Adopting multiple primary outcomes showed a slow growth trend with the publication year. The proportion of primary outcome reported explicitly in RCTs was different in terms of the nationality of the first author (<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>P<\/a:mi>\n                        <a:mo>=<\/a:mo>\n                        <a:mn>0.004<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>), in which mainland China has the lowest proportion (55.8%). The highest percentage of the studies with primary outcome reporting explicitation was mental and behavioural disorders (83.3%), and the most frequently adopting multiple primary outcomes were studies on the disease of the nervous system (66.7%). The percentage of reporting primary outcome explicitly was associated with sample size (<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>P<\/c:mi>\n                        <c:mo>&lt;<\/c:mo>\n                        <c:mn>0.001<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>); for the percentage of RCTs adopting multiple primary outcomes, there was no statistically significant difference (<jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>P<\/e:mi>\n                        <e:mo>=<\/e:mo>\n                        <e:mn>0.739<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>). Conclusions. Multiple primary outcomes are prevalent in CHM RCTs. However, appropriate methods are not usually taken in most of the analyses to safeguard the inferences against multiplicity. Sample size estimation based on multiple primary outcomes is still lacking. These issues complicate the interpretability of trial results and can lead to spurious conclusions. Guidelines to improve analyzing and reporting for multiple primary outcomes in CHM RCTs are warranted.<\/jats:p>","DOI":"10.1155\/2021\/9975351","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T23:42:27Z","timestamp":1619048547000},"page":"1-8","source":"Crossref","is-referenced-by-count":2,"title":["The Use of Multiple Primary Outcomes in Randomized Controlled Trials of Chinese Herbal Medicine"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7080-0212","authenticated-orcid":true,"given":"Jing","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Clinical Epidemiology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9155-4652","authenticated-orcid":true,"given":"Shuo","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-4100","authenticated-orcid":true,"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Editorial Office of Medical Journal of Chinese PLA, Beijing 100842, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2544-4279","authenticated-orcid":true,"given":"Huina","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8144-3329","authenticated-orcid":true,"given":"Yanxiang","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7276-9105","authenticated-orcid":true,"given":"Chongyang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3158-4825","authenticated-orcid":true,"given":"Xuejiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0572-0034","authenticated-orcid":true,"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5745-755X","authenticated-orcid":true,"given":"Xing","family":"Liao","sequence":"additional","affiliation":[{"name":"Center for Evidence Based Chinese Medicine, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-6610","authenticated-orcid":true,"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Beijing Traditional Chinese Medicine Hospital, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9123103"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-018-0167-z"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1177\/2374373517706612"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/s2095-4964(17)60314-5"},{"key":"5","first-page":"24","article-title":"Analysis of the effect of refined Guanxin tablets on 112 patients with angina pectoris","volume":"11","author":"K. Chen","year":"1982","journal-title":"Bulletin of Medical Research"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9461415"},{"key":"7","first-page":"1905","article-title":"Statistical principles for clinical trials. International conference on harmonisation E9 expert working group","volume":"18","author":"ICH Harmonised Tripartite Guideline","year":"1999","journal-title":"Statistics in Medicine"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2006.00437.x"},{"key":"9","first-page":"270","article-title":"Preliminary study of establishing clinical effect evaluation methods of Chinese Medicine based on combination of disease and syndrome, systematic staging, and multi-dimension index","volume":"33","author":"X. Wang","year":"2013","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/202703"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-015-2440-7"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2017.06.06"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/458765"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2010.12.007"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2015.07.016"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2016.09.003"},{"key":"17","article-title":"Primary outcomes reporting in trials of paediatric type 1 diabetes mellitus: a systematic review","volume":"7","author":"S. K. Ardestani","year":"2017","journal-title":"BMJ Open"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5974"},{"key":"19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/9780470316672.ch3","volume-title":"Multiple Comparison Procedures","author":"Y. Hochberg","year":"1987"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.19.2554"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.2307\/2532240"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2015.1006373"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1724"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.2522\/ptj.20140256"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.2522\/ptj.20120206"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.4103\/0366-6999.216407"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c365"},{"article-title":"International standards for clinical trial Registries","year":"2012","author":"WHO","key":"28"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-152-11-201006010-00232"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0258(19971130)16:22<2529::aid-sim692>3.0.co;2-j"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1081\/bip-200067922"},{"key":"32","first-page":"65","article-title":"A simple sequentially rejective multiple test procedure","volume":"6","author":"S. A. Holm","year":"1979","journal-title":"Scand J Stat"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/75.4.800"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2011.11.001"},{"key":"35","first-page":"1214","article-title":"Application of evaluation of multiple primary endpoints based on combination of diseases and symptoms in TCM clinical trials","volume":"12","author":"J. Hu","year":"2017","journal-title":"World Chinese Medicine"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(81)90001-5"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1002\/pst.301"},{"key":"38","first-page":"5322","article-title":"Critical quality evaluation and application value of network Meta-analyses in traditional Chinese medicine","volume":"44","author":"Y. Chen","year":"2019","journal-title":"Chinese Journal of Natural Medicines"},{"key":"39","first-page":"2302","article-title":"Evaluation of methodological quality of traditional Chinese medicine clinical trials","volume":"30","author":"Z. Cui","year":"2019","journal-title":"Lishizhen Medicine and Materia Medica Research"}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/9975351.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/9975351.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/9975351.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T23:42:37Z","timestamp":1619048557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ecam\/2021\/9975351\/"}},"subtitle":[],"editor":[{"given":"Hongcai","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,21]]},"references-count":39,"alternative-id":["9975351","9975351"],"URL":"https:\/\/doi.org\/10.1155\/2021\/9975351","relation":{},"ISSN":["1741-4288","1741-427X"],"issn-type":[{"type":"electronic","value":"1741-4288"},{"type":"print","value":"1741-427X"}],"subject":[],"published":{"date-parts":[[2021,4,21]]}}}