{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:23:46Z","timestamp":1768551826176,"version":"3.49.0"},"posted":{"date-parts":[[2021,3,20]]},"group-title":"Epidemiology","reference-count":14,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Given the absence of a disease-specific biomarker, there are more than 20 symptoms-based case definitions of myalgic encephalomyelitis\/chronic fatigue syndrome. As a consequence, the diagnosis for a given patient could vary from one case definition to another. In this context, we analyse data from a biobank dedicated to this disease in order to study the agreement between different case definitions, the similarity between symptom\u2019s profile among all participants including healthy controls and patients with multiple sclerosis. We also investigate the impact of patients\u2019 misclassification on a hypothetical association analysis using data simulation.<\/jats:p>","DOI":"10.1101\/2021.03.19.21253905","type":"posted-content","created":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T12:55:14Z","timestamp":1616244914000},"source":"Crossref","is-referenced-by-count":5,"title":["Statistical challenges of investigating a disease with a complex diagnosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-1483","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Malato","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-8500","authenticated-orcid":false,"given":"Lu\u00eds","family":"Gra\u00e7a","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-8088","authenticated-orcid":false,"given":"Lu\u00eds","family":"Nacul","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5077-7868","authenticated-orcid":false,"given":"Eliana","family":"Lacerda","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-1706","authenticated-orcid":false,"given":"Nuno","family":"Sep\u00falveda","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2021032211550615000_2021.03.19.21253905v2.1","doi-asserted-by":"crossref","unstructured":"Agresti, Alan . 2002. Categorical Data Analysis. John Wiley & Sons, Inc.","DOI":"10.1002\/0471249688"},{"key":"2021032211550615000_2021.03.19.21253905v2.2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-003973"},{"key":"2021032211550615000_2021.03.19.21253905v2.3","doi-asserted-by":"publisher","DOI":"10.1300\/J092v11n01_02"},{"key":"2021032211550615000_2021.03.19.21253905v2.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2011.02428.x"},{"key":"2021032211550615000_2021.03.19.21253905v2.5","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-12-199412150-00009"},{"key":"2021032211550615000_2021.03.19.21253905v2.6","doi-asserted-by":"crossref","unstructured":"Gower, John C and Matthijs J Warrens. 2014. \u201cSimilarity, dissimilarity, and distance, measures of.\u201d Wiley StatsRef: Statistics Reference Online pp. 1\u201311.","DOI":"10.1002\/9781118445112.stat02470"},{"key":"2021032211550615000_2021.03.19.21253905v2.7","unstructured":"Institute of Medicine (US), Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. 2015. Beyond Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. National Academies Press."},{"key":"2021032211550615000_2021.03.19.21253905v2.8","doi-asserted-by":"crossref","unstructured":"Lacerda, Eliana M. , Kathleen Mudie , Caroline C. Kingdon , Jack D. Butterworth , Shennae O\u2019Boyle , and Luis Nacul . 2018. \u201cThe UK ME\/CFS Biobank: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome.\u201d Frontiers in Neurology 9.","DOI":"10.3389\/fneur.2018.01026"},{"key":"2021032211550615000_2021.03.19.21253905v2.9","doi-asserted-by":"crossref","unstructured":"Morris, Gerwyn and Michael Maes . 2013. \u201cMyalgic encephalomyelitis\/chronic fatigue syndrome and encephalomyelitis disseminata\/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics.\u201d BMC Medicine 11.","DOI":"10.1186\/1741-7015-11-205"},{"key":"2021032211550615000_2021.03.19.21253905v2.10","first-page":"1765","article-title":"How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis\/chronic fatigue syndrome studies?","volume":"24","year":"2017","journal-title":"Journal of Health Psychology"},{"key":"2021032211550615000_2021.03.19.21253905v2.11","doi-asserted-by":"publisher","DOI":"10.1111\/1541-0420.00077"},{"key":"2021032211550615000_2021.03.19.21253905v2.12","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3390\/healthcare8020088","article-title":"The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME\/CFS): A Report from the European Network on ME\/CFS (EUROMENE)","volume":"8","year":"2020","journal-title":"Healthcare"},{"key":"2021032211550615000_2021.03.19.21253905v2.13","doi-asserted-by":"crossref","unstructured":"Rasa, Santa , Zaiga Nora-Krukle , Nina Henning , Eva Eliassen , Evelina Shikova , Thomas Harrer , Carmen Scheibenbogen , Modra Murovska , and Bhupesh K. Prusty . 2018. \u201cChronic viral infections in myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS).\u201d Journal of Translational Medicine 16.","DOI":"10.1186\/s12967-018-1644-y"},{"key":"2021032211550615000_2021.03.19.21253905v2.14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s12967-017-1263-z","article-title":"The European ME\/CFS Biomarker Landscape project: an initiative of the European network EUROMENE","volume":"15","year":"2017","journal-title":"Journal of translational medicine"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2021.03.19.21253905","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:10:59Z","timestamp":1768486259000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2021.03.19.21253905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,20]]},"references-count":14,"URL":"https:\/\/doi.org\/10.1101\/2021.03.19.21253905","relation":{},"subject":[],"published":{"date-parts":[[2021,3,20]]},"subtype":"preprint"}}