{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:42:20Z","timestamp":1783676540909,"version":"3.55.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Prevention of decompensation is a primary therapeutic target in patients with compensated cirrhosis (CC). However, a major problem is the large sample size and long follow\u2010up required to demonstrate a significant treatment effect because of the relatively low baseline risk. For this reason, it has been recently suggested that ordinal outcomes may be used in this area to gain power and reduce sample size. The aim of this study was to assess the applicability of ordinal outcomes in cirrhosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>An inception cohort of 202 patients with CC (no ascites, gastrointestinal bleeding, encephalopathy, or jaundice) without esophageal varices was included, and 5\u2010year outcome is reported. Etiology was mostly viral and alcoholic, and there were no dropouts. Ordinal outcome was set according to six grades with a previously established prognostic ordinality: grade 1\u00a0=\u00a0no disease progression; grade 2\u00a0=\u00a0development of varices; grade 3\u00a0=\u00a0bleeding alone; grade 4\u00a0=\u00a0nonbleeding single decompensation; grade 5\u00a0=\u00a0more than one decompensating event; and grade 6\u00a0=\u00a0death. At the 60\u2010month time point, patients were distributed in grades 1 through 6 as follows: 129, 43, 2, 7, 5, and 16, respectively. Emulation of a clinical trial performed by dividing patients based on baseline platelet count into two groups (cutoff, 150\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/L) demonstrated a statistically significant outcome difference between groups when using ordinal outcomes not detectable by binary logistic or chi\u2010square or time\u2010to\u2010event analyses. Additionally, using ordinal outcomes in a hypothetical study to prevent decompensation resulted in sample\u2010size estimates 3\u2010to 4\u2010fold lower than using a binary composite endpoint.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Compared to traditional binary outcomes, the use of ordinal outcomes in trials of cirrhosis decompensation may provide more power and thus may require a smaller sample size.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31070","type":"journal-article","created":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T16:59:12Z","timestamp":1576342752000},"page":"1029-1042","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":20,"title":["Ordinal Outcomes Are Superior to Binary Outcomes for Designing and Evaluating Clinical Trials in Compensated Cirrhosis"],"prefix":"10.1097","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0430-1786","authenticated-orcid":false,"given":"Gennaro","family":"D\u2019Amico","sequence":"first","affiliation":[{"name":"Gastroenterology Unit,Ospedale V. Cervello, Clinica La Maddalena,Palermo,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan G.","family":"Abraldes","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology (Liver Unit), Department of Medicine,CEGIIR, University of Alberta,Edmonton,AB,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rebora","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia,Universit\u00e0 di Milano\u2010Bicocca,Milano,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Valsecchi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia,Universit\u00e0 di Milano\u2010Bicocca,Milano,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guadalupe","family":"Garcia\u2010Tsao","sequence":"additional","affiliation":[{"name":"Section of Digestive Diseases,Yale University School of Medicine\/VA\u2010CT Healthcare System,New Haven,CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"hep31070-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jhep.2005.10.013","article-title":"Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies","volume":"44","year":"2006","journal-title":"J Hepatol"},{"key":"hep31070-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/hep.30314","article-title":"Prioritization of therapeutic targets and trial design in cirrhotic portal hypertension","volume":"69","year":"2019","journal-title":"Hepatology"},{"key":"hep31070-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/S0140-6736(18)31875-0","article-title":"\u0392\u2010blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double\u2010blind, placebo\u2010controlled, multicentre trial","volume":"393","year":"2019","journal-title":"Lancet"},{"key":"hep31070-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1056\/NEJMoa044456","article-title":"Beta\u2010blockers to prevent gastroesophageal varices in patients with cirrhosis","volume":"353","year":"2005","journal-title":"N Engl J Med"},{"key":"hep31070-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0895-4356(96)00312-5","article-title":"Statistical assessment of ordinal outcomes in comparative studies","volume":"50","year":"1997","journal-title":"J Clin Epidemiol"},{"key":"hep31070-bib-0006-20241017","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1089\/neu.2005.22.511","article-title":"Design and analysis of phase III trials with ordered outcome scales: the concept of the sliding dichotomy","volume":"22","year":"2005","journal-title":"J Neurotrauma"},{"key":"hep31070-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/hep.28264","article-title":"Development of hyperdynamic circulation and response to \u03b2\u2010blockers in compensated cirrhosis with portal hypertension","volume":"63","year":"2016","journal-title":"Hepatology"},{"key":"hep31070-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.jhep.2017.12.027","article-title":"Cardiopulmonary hemodynamics and C\u2010reactive protein as prognostic indicators in compensated and decompensated cirrhosis","volume":"68","year":"2018","journal-title":"J Hepatol"},{"key":"hep31070-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.jhep.2015.07.004","article-title":"Mechanisms of decompensation and organ failure in cirrhosis: from peripheral arterial vasodilatation to systemic inflammation hypothesis","volume":"63","year":"2015","journal-title":"J Hepatol"},{"key":"hep31070-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.jhep.2017.10.020","article-title":"Clinical states of cirrhosis and competing risks","volume":"68","year":"2018","journal-title":"J Hepatol"},{"key":"hep31070-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"R127","DOI":"10.1186\/cc10240","article-title":"The added value of ordinal analysis in clinical trials: an example in traumatic brain injury","volume":"15","year":"2011","journal-title":"Crit Care"},{"key":"hep31070-bib-0013-20241017","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1111\/apt.12721","article-title":"Competing risks and prognostic stages in cirrhosis: a 25\u2010year inception cohort study of 494 patients","volume":"39","year":"2014","journal-title":"Aliment Pharmacol Ther"},{"key":"hep31070-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1258\/RSMSMJ.53.1.44","article-title":"Dr John Rankin; 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