Dataset Information

Characteristics and publication fate of unregistered and retrospectively registered clinical trials submitted to The BMJ over 4 years.

ABSTRACT: We sought to evaluate the characteristics and publication fate of improperly registered clinical trials submitted to a medical journal (The BMJ) over a 4-year period to identify common types of registration issues and their relation to publication outcomes.Research articles submitted to The BMJ and identified as unregistered or retrospectively registered by editors were included if they reported outcomes of a clinical trial. Relevant data regarding the trials were then extracted from each paper. Trials were categorised as prospectively registered, registered in an unapproved registry, unregistered or other, and explanations for registration deficiencies were grouped into six categories. We searched PubMed and Google to determine whether, where and when improperly registered studies were subsequently published and whether registration issues were disclosed.123 research papers reporting apparently unregistered or retrospectively registered clinical trials were identified. 110 studies (89.4%) were retrospectively registered, nine (7.3%) were unregistered, three (2.4%) had been registered in an unapproved registry and one study originally lacking registration details was later discovered to have been prospectively registered. 82 studies (66.6%) were funded entirely or in part by government sources, and only seven studies (5.7%) received funding from industry. Of those papers submitted to The BMJ through the end of 2015, 67 of the 70 papers rejected for registration problems (95.7%) were subsequently published in another journal. The registration problem was disclosed in only 2 (2.9%).Improper registration remains a problem, particularly for clinical trials that are government or foundation-funded. Nonetheless, improperly registered trials are almost always published, suggesting that medical journal editors may not actively enforce registration requirements.

SUBMITTER: Loder E

PROVIDER: S-EPMC5829901 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

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Characteristics and publication fate of unregistered and retrospectively registered clinical trials submitted to <i>The BMJ</i> over 4 years.

Loder Elizabeth E Loder Stephen S Cook Sophie S

BMJ open 20180216 2

<h4>Objectives</h4>We sought to evaluate the characteristics and publication fate of improperly registered clinical trials submitted to a medical journal (<i>The BMJ</i>) over a 4-year period to identify common types of registration issues and their relation to publication outcomes.<h4>Design</h4>Research articles submitted to <i>The BMJ</i> and identified as unregistered or retrospectively registered by editors were included if they reported outcomes of a clinical trial. Relevant data regarding ...[more]

PMID: 29453302

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Project description:ImportanceThe published evidence in support of probiotic use is conflicting, which may be a result of selective publication of probiotic trials.ObjectivesTo compare the proportion of registered trials that evaluate pediatric probiotics vs those that evaluate antibiotics that are published and to identify study-related factors associated with publication status.Design, setting, and participantsThis cross-sectional study evaluated eligible trials registered in ClinicalTrials.gov, an online clinical trials registry, from July 1, 2005, to June 30, 2016. Eligible studies included participants younger than 18 years, evaluated a probiotic or 1 of the 5 most commonly prescribed antibiotics in children and adolescents, and randomized study participants. All searches were updated and finalized as of September 9, 2020.ExposuresProbiotic or antibiotic.Main outcomes and measuresThe primary outcome was study publication status. In addition, exposure status (probiotic vs antibiotic), trial result, and funding source were assessed for independent association with publication status. Whether study design elements, publication journal impact factor, and the interval from study completion to publication differed by exposure status were also evaluated.ResultsA total of 401 unique trials (265 probiotic and 136 antibiotic) met eligibility criteria. A greater proportion of antibiotic compared with probiotic studies were published (83 [61.0%] vs 119 [44.9%]; difference, 16.1% [95% CI, 5.8%-25.9%]). After adjustment for funding source, blinding, and purpose, studies evaluating an antibiotic were more likely to be published (odds ratio, 2.1 [95% CI, 1.3-3.4]). No other covariates included in the model were independently associated with publication status. Antibiotic trials, compared with probiotic trials, were more likely to have a therapeutic purpose (114 [83.8%] vs 117 [44.2%]; difference, 39.6% [95% CI, 31.1%-48.3%]) and to be multicenter (46 [33.8%] vs 46 [17.4%]; difference, 16.5% [95% CI, 7.5%-25.7%]). The median impact factor of the journals in which the studies were published was higher for the antibiotic trials (7.2 [IQR, 2.8-20.5] vs 3.0 [IQR, 2.3-4.2]; P < .001). The median number of days to publication did not differ between the probiotic and antibiotic trials (683 [IQR, 441-1036] vs 801 [IQR, 550-1183]; P = .24).Conclusions and relevanceThe findings of this cross-sectional study suggest that probiotic studies are less likely to be published than antibiotic trials. No other study characteristics were associated with publication status. This finding raises concerns regarding the results of meta-analyses of probiotic trials.

Project description:ImportancePublishing study protocols might reduce research waste because of unclear methods or incomplete reporting; on the other hand, there might be few additional benefits of publishing protocols for registered trials that are never completed or published. No study has investigated the proportion of published protocols associated with published results.ObjectiveTo estimate the proportion of published trial protocols for which there are not associated published results.Design, setting, and participantsThis cross-sectional study used stratified random sampling to identify registered clinical trials with protocols published between January 2011 and August 2022 and indexed in PubMed Central. Ongoing studies and those within 1 year of the primary completion date on ClinicalTrials.gov were excluded. Published results were sought from August 2022 to March 2023 by searching ClinicalTrials.gov, emailing authors, and using an automated tool, as well as through incidental discovery.Main outcomes and measuresThe primary outcome was a weighted estimate of the proportion of registered trials with published protocols that also had published main results. The proportion of trials with unpublished results was estimated using a weighted mean.ResultsFrom 1500 citations that were screened, 308 clinical trial protocols were included, and it was found that 87 trials had not published their main results. Most included trials were investigator-initiated evaluations of nonregulated products. When published, results appeared a mean (SD) of 3.4 (2.0) years after protocol publications. With the use of a weighted mean, an estimated 4754 (95% CI, 4296-5226) eligible clinical trial protocols were published and indexed in PubMed Central between 2011 and 2022. In the weighted analysis, 1708 of those protocols (36%; 95% CI, 31%-41%) were not associated with publication of main results. In a sensitivity analysis excluding protocols published after 2019, an estimated 25% (95% CI, 20%-30%) of 3670 (95% CI, 3310-4032) protocol publications were not associated with publication of main results.Conclusions and relevanceThis cross-sectional study of clinical trial protocols published on PubMed Central between 2011 and 2022 suggests that many protocols were not associated with subsequent publication of results. The overall benefits of publishing study protocols might outweigh the research waste caused by unnecessary protocol publications.

Project description: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.

Project description:ObjectivesDue to the rapid spread of COVID-19 worldwide, many countries have designed clinical trials to find efficient treatments. We aimed to critically report the characteristics of all the registered and published randomized clinical trials (RCTs) conducted on COVID-19, and summarize the evaluation of potential therapies developed in various regions.Evidence acquisitionWe comprehensively searched PubMed, Cochrane Library, Web of Science, Scopus, and Clinicaltrial.gov databases to retrieve all the relevant studies up to July 19, 2021, in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. We included all English-language published/registered RCTs on COVID-19, and excluded non-RCT, in-vitro/in-vivo, editorials, and review studies. Two reviewers independently evaluated all the records, and then analyzed by using SPSS 17.ResultsWithin 3018 included studies, 2801 (92.8%) and 217 (7.2%) were registered or published RCTs consisting of about 600 synthetic drugs. Herbal medicines have been studied in 23 trials (10.6%) among the published RCTs and in 357 registered RCTs (12.7%). Hydroxychloroquine 23 (10.6%) and convalescent plasma 194 (6.9%) alone or in combination with other agents were the most frequently used interventions in published and registered RCTs, respectively. Most published RCTs have been conducted in Western Pacific Region (WPRO) (50 trials, 23.0%) including 45 trials from China. Also, a greater proportion of registered RCTs have been conducted in the Region of the Americas (PAHO) (885 trials, 31.6%) including 596 RCTs from the United States (U.S). Globally, 283 registered trials have been conducted to assess new developed vaccines for COVID or previously established for other disorders.ConclusionThe present study highlighted the wide range of potential therapeutic agents in published and registered COVID-19 clinical trials across a wide range of regions. However, it is urgently required to global coordination in order to conduct more well-designed trials and progress in discovering safe and effective treatments.

Project description:ObjectivesThe coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19.Design, setting and participantsCross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers.Main outcomesTrial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020.ConclusionsWhile accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.

Project description:The COVID-19 pandemic has unleashed a deluge of publications. For this cross-sectional study we compared the amount and reporting characteristics of COVID-19-related academic articles and preprints and the number of ongoing clinical trials and systematic reviews. To do this, we searched the PubMed database of citations and abstracts for published life science journals by using appropriate combinations of medical subject headings (MeSH terms), and the COVID-19 section of the MedRxiv and BioRxiv archives up to 20 May 2020 (21 weeks). In addition, we searched Clinicaltrial.gov, Chinese Clinical Trial Registry, EU Clinical Trials Register, and 15 other trial registers, as well as PROSPERO, the international prospective register of systematic reviews. The characteristics of each publication were extracted. Regression analyses and Z tests were used to detect publication trends and their relative proportions. A total of 3635 academic publications and 3805 preprints were retrieved. Only 8.6% (n = 329) of the preprints were already published in indexed journals. The number of academic and preprint publications increased significantly over time (p<0.001). Case reports (6% academic vs 0.9% preprints; p<0.001) and letters (17.4% academic vs 0.5% preprints; p<0.001) accounted for a greater share of academic compared to preprint publications. Differently, randomized controlled trials (0.22% vs 0.63%; p<0.001) and systematic reviews (0.08% vs 5%) made up a greater share of the preprints. The relative proportion of clinical studies registered at Clinicaltrials.gov, Chinese Clinical Trial Registry, and EU Clinical Trials Register was 57.9%, 49.5%, and 98.9%, respectively, most of which were still "recruiting". PROSPERO listed 962 systematic review protocols. Preprints were slightly more prevalent than academic articles but both were increasing in number. The void left by the lack of primary studies was filled by an outpour of immediate opinions (i.e., letters to the editor) published in PubMed-indexed journals. Summarizing, preprints have gained traction as a publishing response to the demand for prompt access to empirical, albeit not peer-reviewed, findings during the present pandemic.

Dataset Information

Characteristics and publication fate of unregistered and retrospectively registered clinical trials submitted to The BMJ over 4 years.

Publications

Characteristics and publication fate of unregistered and retrospectively registered clinical trials submitted to <i>The BMJ</i> over 4 years.

Similar Datasets

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