{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T13:42:37Z","timestamp":1782826957717,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,3,11]],"date-time":"2014-03-11T00:00:00Z","timestamp":1394496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The recent <jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content> provisional endpoint incorporates a one\u2010tailed measure of improvement for <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content> based on the underlying motility complaint. However, motility exists along a spectrum. Patients may experience diarrhoea resulting from therapy for their constipation\u2010predominant <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010C) or constipation during treatment for diarrhoea\u2010predominant <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D), but still meet a unidirectional motility\u2010based <jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content> endpoint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To weigh the reported efficacy of existing therapies based on patient\u2010reported outcomes with negative intestinal side effects in controlled clinical trial data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed the difference between \u2018attributable risk\u2019 of efficacy based on number needed to treat (<jats:styled-content style=\"fixed-case\">NNT<\/jats:styled-content>) in the literature and percentage of adverse events (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>) of opposite intestinal complaints in placebo\u2010controlled trials identified through a literature search of <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content> trials. This calculation was coined \u2018functional net value\u2019 (<jats:styled-content style=\"fixed-case\">FNV<\/jats:styled-content>) or net benefit of the given drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For treating <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010C, lubiprostone caused diarrhoea in excess of placebo in 3.9% of patients, leading to a <jats:styled-content style=\"fixed-case\">FNV<\/jats:styled-content> of 3.9 percentage units. Linaclotide caused diarrhoea in 15.3% resulting in negative <jats:styled-content style=\"fixed-case\">FNV<\/jats:styled-content> (\u22121.0 percentage unit). For <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D, alosetron and tricyclic anti\u2010depressants caused constipation among a respective 16.9% and 13.0% resulting in a <jats:styled-content style=\"fixed-case\">FNV<\/jats:styled-content> of \u22123.6 and \u22120.5 percentage units. Among all therapies, only rifaximin did not cause the adverse event opposite the underlying motility complaint and the drug only had benefit, not detriment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Functional net value (<jats:styled-content style=\"fixed-case\">FNV<\/jats:styled-content>) offers a method of evaluating the net benefit of a drug in <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>. Most <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content> treatments have a negative effect on <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content> that exceeds the benefits.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.12692","type":"journal-article","created":{"date-parts":[[2014,3,11]],"date-time":"2014-03-11T05:23:53Z","timestamp":1394515433000},"page":"973-983","source":"Crossref","is-referenced-by-count":9,"title":["Evaluating the functional net value of pharmacologic agents in treating irritable bowel syndrome"],"prefix":"10.1111","volume":"39","author":[{"given":"E.","family":"Shah","sequence":"first","affiliation":[{"name":"GI Motility Program Cedars\u2010Sinai Medical Center Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Pimentel","sequence":"additional","affiliation":[{"name":"GI Motility Program Cedars\u2010Sinai Medical Center Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1207068"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.061"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010770302403"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.suppl_1.i29"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.678"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-007-9977-z"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e5836"},{"key":"e_1_2_7_9_1","first-page":"CD003460","article-title":"Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome","volume":"8","author":"Ruepert L","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.355"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.03.004"},{"key":"e_1_2_7_12_1","unstructured":"Committee for Medicinal Products for Human Use (CHMP).Concept paper on the revision of the CHMP points to consider on the evaluation of medicinal products for the treatment of irritable bowel syndrome (CPMP\/EWP\/785\/97). 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