{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:47:48Z","timestamp":1781322468554,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T00:00:00Z","timestamp":1629504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01ZX1909"],"award-info":[{"award-number":["01ZX1909"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR265"],"award-info":[{"award-number":["TRR265"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no \u201cspontaneous improvement\u201d prior to treatment initiation (high\u2010severity population) than in a mild\u2010severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a systematic literature review on placebo\u2010controlled RCTs for AD.We assigned retained RCTs to high\u2010 or mild\u2010severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta\u2010regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 19 retained RCTs (comprising 1996 placebo\u2010treated patients), 11 trials were high\u2010severity and 8 were mild\u2010severity RCTs. The between\u2010study variability in AR was lower in the high\u2010severity than in the mild\u2010severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.004) and treatment duration (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.017) and was lower in the high\u2010severity studies (16.8% at 3\u00a0months) than the mild\u2010severity studies (36.7% at 3\u00a0months).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pharmacological RCTs for AD should select high\u2010severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14670","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T18:21:32Z","timestamp":1631643692000},"page":"1722-1734","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta\u2010regression analysis to develop an enrichment strategy"],"prefix":"10.1111","volume":"45","author":[{"given":"Bruno","family":"Scherrer","sequence":"first","affiliation":[{"name":"Bruno Scherrer Conseil Saint Arnoult en Yvelines France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1284-7949","authenticated-orcid":false,"given":"Julien","family":"Guiraud","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Amsterdam Neuroscience Amsterdam UMC University of Amsterdam Amsterdam The Netherlands"},{"name":"DA Pharma Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1522-9946","authenticated-orcid":false,"given":"Giovanni","family":"Addolorato","sequence":"additional","affiliation":[{"name":"Alcohol Use Disorder and Alcohol Related Disease Unit Department of Internal Medicine and Gastroenterology Fondazione Policlinico Universitario A.Gemelli IRCCS Rome Italy"},{"name":"Internal Medicine Unit Department of Internal Medicine and Gastroenterology Columbus\u2010Gemelli Hospital Fondazione Policlinico Universitario A. 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