{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:35:48Z","timestamp":1782189348775,"version":"3.54.5"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Clinical trials can terminate early for many reasons, including non-scientific reasons. We aimed to develop scalable semi-automated methods to characterize terminated trials and explore a methodology to estimate the risk of experiencing serious adverse events (SAEs) in trials terminated due to non-scientific reasons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two cohorts of clinical trials registered in ClinicalTrials.gov were investigated: (1) a cohort of clinical trials affiliated with German university medical centers (reported as completed between 2009\u20132017) and (2) a cohort of clinical trials affiliated with Californian university medical centers (reported as completed between 2014\u20132017). We used these cohorts to explore scalable assessment methods and compare terminated trials to completed ones regarding trial characteristics, including therapeutic focus. In a subset of trials terminated for non-scientific reasons with tabular summary results and a parallel, randomized design, we estimated additional risk for SAE. For the German cohort, if results were missing from ClinicalTrials.gov, results from the EU Clinical Trials Register (EUCTR) were included if available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 2,253 German and 1,091 Californian trials, 217 (10%) and 150 (14%) were terminated, respectively. The majority (German: 65%, Californian: 67%) cited non-scientific reasons for termination, primarily low accrual. Compared to completed trials, terminated trials showed lower rates of results reporting: 35% vs. 78% in Germany and 72% vs. 87% in California. Of 242 trials terminated for non-scientific reasons, 14 (6%; 11 from ClinicalTrials.gov, 3 from EUCTR) could be included in the SAE risk assessment. In this limited exploratory analysis, no difference in SAE risk was observed between the intervention and control arms (RR 1.05, 95% CI: 0.76\u20131.44).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Results of terminated trials were less frequently reported, limiting opportunities for knowledge generation. Broader adoption of harmonized result reporting standards across registries, structured templates, and improved logic checks could enable scalable assessment approaches and enhance the utility of terminated trial data for clinical research transparency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0346608","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:36:07Z","timestamp":1776274567000},"page":"e0346608","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring scalable assessment methods for terminated trials in ClinicalTrials.gov: A cohort analysis of German and Californian trials"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0748-383X","authenticated-orcid":true,"given":"Samruddhi Suresh","family":"Yerunkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8975-0649","authenticated-orcid":true,"given":"Benjamin Gregory","family":"Carlisle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delwen L.","family":"Franzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia","family":"Salholz-Hillel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Strech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne Gabriele","family":"Schorr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"issue":"4","key":"pone.0346608.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1003980","article-title":"Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis","volume":"19","author":"B Speich","year":"2022","journal-title":"PLoS Med"},{"issue":"2","key":"pone.0346608.ref002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2000487","article-title":"Inefficiencies and Patient Burdens in the Development of the Targeted Cancer Drug Sorafenib: A Systematic Review","volume":"15","author":"J Mattina","year":"2017","journal-title":"PLoS Biol"},{"key":"pone.0346608.ref003","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jclinepi.2019.06.002","article-title":"Result dissemination from clinical trials conducted at German university medical centers was delayed and incomplete","volume":"115","author":"S Wieschowski","year":"2019","journal-title":"J Clin Epidemiol"},{"issue":"4","key":"pone.0346608.ref004","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2021-052557","article-title":"Early Discontinuation, Results Reporting, and Publication of Pediatric Clinical Trials","volume":"149","author":"R Brewster","year":"2022","journal-title":"Pediatrics"},{"issue":"5","key":"pone.0346608.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0127242","article-title":"Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination","volume":"10","author":"RJ Williams","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"pone.0346608.ref006","article-title":"Population Analysis of Adverse Events in Different Age Groups Using Big Clinical Trials Data","volume":"4","author":"J Luo","year":"2016","journal-title":"JMIR Med Inform"},{"key":"pone.0346608.ref007","unstructured":"U.S. Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE) version 4.0. 2009."},{"issue":"12","key":"pone.0346608.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001566","article-title":"Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals","volume":"10","author":"C Riveros","year":"2013","journal-title":"PLoS Med"},{"issue":"4","key":"pone.0346608.ref009","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1177\/17407745221093567","article-title":"Reporting of clinical trial safety results in ClinicalTrials.gov for FDA-approved drugs: A cross-sectional analysis","volume":"19","author":"KY Chen","year":"2022","journal-title":"Clin Trials"},{"key":"pone.0346608.ref010","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12916-015-0430-4","article-title":"Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles","volume":"13","author":"E Tang","year":"2015","journal-title":"BMC Med"},{"key":"pone.0346608.ref011","doi-asserted-by":"crossref","first-page":"101277","DOI":"10.1016\/j.conctc.2024.101277","article-title":"A retrospective analysis of serious adverse events and deaths in U.S.-based lifestyle clinical trials for cognitive health","volume":"38","author":"MN Key","year":"2024","journal-title":"Contemp Clin Trials Commun"},{"key":"pone.0346608.ref012","article-title":"Registration and Reporting of Clinical Trials Affiliated with California Universities and with Primary Completion Date from 2014 to 2017","author":"MVN Mali\u010dki","year":"2025","journal-title":"medRxiv"},{"key":"pone.0346608.ref013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jclinepi.2021.12.012","article-title":"Results dissemination from completed clinical trials conducted at German university medical centers remained delayed and incomplete. The 2014 -2017 cohort.","volume":"144","author":"N Riedel","year":"2022","journal-title":"J Clin Epidemiol"},{"issue":"12","key":"pone.0346608.ref014","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.ijsu.2014.07.013","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies","volume":"12","author":"E von Elm","year":"2014","journal-title":"Int J Surg"},{"key":"pone.0346608.ref015","author":"M Salholz-Hillel"},{"key":"pone.0346608.ref016","article-title":"Responsible Metrics dashboard for clinical research transparency GitHub","author":"V Nachev"},{"issue":"7","key":"pone.0346608.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0270909","article-title":"Analysis of clinical trial registry entry histories using the novel R package cthist","volume":"17","author":"BG Carlisle","year":"2022","journal-title":"PLoS One"},{"key":"pone.0346608.ref018","unstructured":"ClinicalTrials.gov. Protocol Registration Data Element Definitions for Interventional and Observational Studies. https:\/\/clinicaltrials.gov\/policy\/protocol-definitions"},{"key":"pone.0346608.ref019","author":"Y Samruddhi","year":"2023"},{"issue":"2","key":"pone.0346608.ref020","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2019-034306","article-title":"Patient burden and clinical advances associated with postapproval monotherapy cancer drug trials: a retrospective cohort study","volume":"10","author":"BG Carlisle","year":"2020","journal-title":"BMJ Open"},{"issue":"3","key":"pone.0346608.ref021","first-page":"197","article-title":"Bioethics in Practice: Considerations for Stopping a Clinical Trial Early","volume":"16","author":"RE Deichmann","year":"2016","journal-title":"Ochsner J"},{"key":"pone.0346608.ref022","doi-asserted-by":"crossref","first-page":"100922","DOI":"10.1016\/j.bas.2022.100922","article-title":"Is there resource wastage in the research for spinal diseases? An observational analysis of discontinuation and non-publication in randomised controlled trials","volume":"2","author":"AK Demetriades","year":"2022","journal-title":"Brain Spine"},{"key":"pone.0346608.ref023","unstructured":"Guideline for good clinical practice E6(R2). 2016."},{"key":"pone.0346608.ref024","unstructured":"Clinical Trials Transformation Initiative. Aggregate Analysis of ClinicalTrials.gov (AACT) Database. Durham, NC: Clinical Trials Transformation Initiative. https:\/\/aact.ctti-clinicaltrials.org\/"},{"issue":"7","key":"pone.0346608.ref025","doi-asserted-by":"crossref","first-page":"477","DOI":"10.7326\/M13-0480","article-title":"Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications","volume":"160","author":"DM Hartung","year":"2014","journal-title":"Ann Intern Med"},{"key":"pone.0346608.ref026","author":"Y Samruddhi","year":"2023"},{"key":"pone.0346608.ref027","unstructured":"Numbat meta-analysis extraction manager. http:\/\/bgcarlisle.github.io\/Numbat\/"},{"key":"pone.0346608.ref028","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2022"},{"issue":"1","key":"pone.0346608.ref029","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/ehf2.13099","article-title":"Discontinuation and non-publication of heart failure randomized controlled trials: a call to publish all trial results","volume":"8","author":"MS Khan","year":"2021","journal-title":"ESC Heart Fail"},{"issue":"5","key":"pone.0346608.ref030","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0251898","article-title":"Prevention of post-traumatic stress disorder: Lessons learned from a terminated RCT of prolonged exposure","volume":"16","author":"M Bragesj\u00f6","year":"2021","journal-title":"PLoS One"},{"issue":"1","key":"pone.0346608.ref031","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ijsu.2011.10.001","article-title":"CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials","volume":"10","author":"D Moher","year":"2012","journal-title":"Int J Surg"},{"issue":"4","key":"pone.0346608.ref032","article-title":"Reporting summary results in clinical trial registries: updated guidance from WHO","volume":"13","author":"A-W Chan","year":"2025","journal-title":"Lancet Glob Health"},{"key":"pone.0346608.ref033","article-title":"Reporting summary results in clinical trial registries: updated guidance from WHO","author":"World Health Organization","year":"2022","journal-title":"Geneva: World Health Organization"},{"issue":"19","key":"pone.0346608.ref034","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1001\/archinternmed.2009.306","article-title":"Reporting of safety results in published reports of randomized controlled trials","volume":"169","author":"I Pitrou","year":"2009","journal-title":"Arch Intern Med"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0352277","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000}}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346608","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:36:15Z","timestamp":1776274575000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346608"}},"subtitle":[],"editor":[{"given":"Sascha","family":"K\u00f6pke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0346608","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}