title: Non-Publication Is Common among Phase 1, Single-Center, Not Prospectively Registered, or Early Terminated Clinical Drug Trials.
abstract: The objective of this study was to investigate the occurrence and determinants of non-publication of clinical drug trials in the Netherlands.All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followed-up from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination. The main outcome was publication as peer reviewed article. The percentage of trials that were published, crude and adjusted odds ratio (OR), and 95% confidence interval (CI) were used to quantify the associations between determinants and publication. In 2007, 622 clinical drug trials were reviewed by IRBs in the Netherlands. By the end of follow-up, 19 of these were rejected by the IRB, another 19 never started inclusion, and 10 were still running. Of the 574 trials remaining in the analysis, 334 (58%) were published as peer-reviewed article. The multivariable logistic regression model identified the following determinants with a robust, statistically significant association with publication: phase 2 (60% published; adjusted OR 2.6, 95% CI 1.1-5.9), phase 3 (73% published; adjusted OR 4.1, 95% CI 1.7-10.0), and trials not belonging to phase 1-4 (60% published; adjusted OR 3.2, 95% CI 1.5 to 6.5) compared to phase 1 trials (35% published); trials with a company or investigator as applicant (63% published) compared to trials with a Contract Research Organization (CRO) as applicant (50% published; adjusted OR 1.7; 95% CI 1.1-2.8); and multicenter trials also conducted in other EU countries (68% published; adjusted OR 2.2, 95% CI 1.1-4.4) or also outside the European Union (72% published; adjusted OR 2.0, 95% CI 1.0-4.0) compared to single-center trials (45% published). Trials that were not prospectively registered (48% published) had a lower likelihood of publication compared to prospectively registered trials (75% published; adjusted OR 0.5, 95% CI 0.3-0.8), as well as trials that were terminated early (33% published) compared to trials that were completed as planned (64% published; adjusted OR 0.2, 95% CI 0.1-0.3). The non-publication rate of clinical trials seems to have improved compared to previous inception cohorts, but is still far from optimal, in particular among phase 1, single-center, not prospectively registered, and early terminated trials.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, TB Utrecht, The Netherlands.|Central Committee on Research involving Human Subjects (CCMO), BH The Hague, the Netherlands.|National Institute for Public Health and the Environment (RIVM), Division of Public Health and Health Services, BA Bilthoven, The Netherlands.
authors.forename: Cornelis A
authors.identifier: http://orcid.org/0000-0003-0588-5218
authors.initials: CA
authors.lastname: van den Bogert
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, TB Utrecht, The Netherlands.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Souverein
authors.affiliation: Central Committee on Research involving Human Subjects (CCMO), BH The Hague, the Netherlands.
authors.forename: Cecile T M
authors.initials: CT
authors.lastname: Brekelmans
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Division of Public Health and Health Services, BA Bilthoven, The Netherlands.
authors.forename: Susan W J
authors.initials: SW
authors.lastname: Janssen
authors.affiliation: Central Committee on Research involving Human Subjects (CCMO), BH The Hague, the Netherlands.
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koëter
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, TB Utrecht, The Netherlands.
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.affiliation: VU University Medical Center, Department of Epidemiology and Biostatistics, MB Amsterdam, the Netherlands.
authors.forename: Lex M
authors.initials: LM
authors.lastname: Bouter
mesh_terms: D000465:Algorithms; D015706:Bibliometrics; D017321:Clinical Trials, Phase I as Topic; D017277:Drug Approval; D004341:Drug Evaluation; D028744:Ethics Committees, Research; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D009426:Netherlands; D016017:Odds Ratio; D010380:Peer Review; D011643:Publishing / Q000706:statistics & numerical data*