Precision and negative predictive value of links between ClinicalTrials.gov and PubMed.
ABSTRACT: One of the goals of translational science is to shorten the time from discovery to clinical use. Clinical trial registries were established to increase transparency in completed and ongoing clinical trials, and they support linking trials with resulting publications. We set out to investigate precision and negative predictive value (NPV) of links between ClinicalTrials.gov (CT.gov) and PubMed. CT.gov has been established to increase transparency in clinical trials and the link to PubMed is crucial for supporting a number of important functions, including ascertaining publication bias. We drew a random sample of trials downloaded from CT.gov and performed manual review of retrieved publications. We characterize two types of links between trials and publications (NCT-link originating from MEDLINE and PMID-link originating from CT.gov).The link precision is different based on type (NCT-link: 100%; PMID-link: 63% to 96%). In trials with no linked publication, we were able to find publications 44% of the time (NPV=56%) by searching PubMed. This low NPV shows that there are potentially numerous publications that should have been formally linked with the trials. Our results indicate that existing trial registry and publisher policies may not be fully enforced. We suggest some automated methods for improving link quality.
Project description:BACKGROUND: Diseases of the kidneys and genitourinary tract are common health problems that affect people of all ages and demographic backgrounds. In this study, we compared the quantity and quality of nephrological and urological articles published in international journals from the three major regions of China: the mainland (ML), Hong Kong (HK), and Taiwan (TW). METHODS: Nephrological and urological articles originating from ML, TW, and HK that were published in 61 journals from 1999-2008 were retrieved from the PubMed database. We recorded the numbers of total articles, clinical trials, randomized controlled trials, case reports, impact factors (IF), citations, and articles published in the leading general-medicine journals. We used these data to compare the quantity and quality of publication output from the three regions. RESULTS: The total number of articles increased significantly from 1999 to 2008 in the three regions. The number of articles from ML has exceeded that from HK since 2004, and surpassed that from TW in 2008. Publications from TW had the highest accumulated IF, total citations of articles, and the most articles published in leading general-medicine journals. However, HK publications had the highest average IF. Although ML produced the largest quantity of articles, it exhibited the lowest quality among the three regions. CONCLUSION: The number of nephrological and urological publications originating from the three major regions of China increased significantly from 1999 to 2008. The annual number of publications by ML researchers exceeded those from TW and HK. However, the quality of articles from TW and HK was higher than that from ML.
Project description:We wanted to investigate the frequency of undisclosed changes in the outcomes of randomized controlled trials (RCTs) between trial registration and publication.Using a retrospective, nonrandom, cross-sectional study design, we investigated RCTs published in consecutive issues of 5 major medical journals during a 6-month period and their associated trials registry entries. Articles were excluded if they did not have an available trial registry entry, did not have analyzable outcomes, or were secondary publications. The primary outcome was the proportion of publications in which the primary outcome of the trial was, without disclosure, changed between that recorded in the trial registry and that reported in the final publication. The secondary outcome was the proportion of publications in which the secondary outcome was changed without disclosure.We reviewed 158 reports of RCTs and included 110 in the analysis. In 34 (31%), a primary outcome had been changed, and in 77 (70%), a secondary outcome had been changed.There are substantial and important undisclosed changes made to the outcomes of published RCTs between trial registration and publication. This finding has important implications for the interpretation of trial results. Disclosure and discussion of changes would improve transparency in the performance and reporting of trials.
Project description:OBJECTIVES:To examine 1) the publication rate of registered otology trials in ClinicalTrials.gov, 2) the public availability of the results, 3) the study characteristics associated with publication, and 4) the time to publication after trial completion. BACKGROUND:Publication bias, the publication or non-publication of research findings, depending on the nature and direction of results, is accountable for wrong treatment decisions. The extent of publication bias in otology trials has not been evaluated. METHODS:All registered otology trials were extracted from ClinicalTrials.gov with completion date up to December 2015. A search strategy was used to identify corresponding publications up to June 2017, providing at least 18 months to publish the results after trial completion. Characteristics were obtained from ClinicalTrials.gov and corresponding publications. Regression models were used to examine study characteristics associated with publication or non-publication. RESULTS:From the 419 trials identified on ClinicalTrials.gov, 225 (53.7%) corresponding publications were found in PubMed. Among these, 109 (48.4%) publications were cited on ClinicalTrials.gov and 124 (55.1%) articles reported the National Clinical Trial registry number. For 36 (8.6%) trials, results were only reported in ClinicalTrials.gov. Trials with a biological intervention were more likely to be published than studies involving drugs (odds ratio (OR) 10.41, 95% confidence interval (CI) 1.26-86.22, P = 0.030). Trials funded by industry were less likely to be published (OR 0.46, CI 0.25-0.84, P = 0.011). The median trial duration was 20 months (interquartile range (IQR) 26 months), and median time from trial completion to publication was 24 months (IQR 22 months). CONCLUSION:In 37.7% of the registered otology trials the results remained unpublished, even several years after trial completion. With little citations on ClinicalTrials.gov and low reporting of the Clinical Trial registry number, the accessibility is limited. Our findings show that there is room for improvement in accuracy of trial registration and publication of results, in order to diminish publication bias in otology studies.
Project description:Research on stem cells (SC) is growing rapidly in neurology, but clinical applications of SC for neurological disorders remain to be proven effective and safe. Human clinical trials need to be registered in registries in order to reduce publication bias and selective reporting.We searched three databases-clinicaltrials.gov, the Clinical Research Information System (CRIS), and PubMed-for neurologically relevant SC-based human trials and articles in Korea. The registration of trials, posting and publication of results, and registration of published SC articles were examined.There were 17 completed trials registered at clinicaltrials.gov and the CRIS website, with results articles having been published for 5 of them. Our study found 16 publications, of which 1 was a review article, 1 was a protocol article, and 8 contained registered trial information.Many registered SC trials related to neurological disorders are not reported, while many SC-related publications are not registered in a public registry. These results support the presence of biased reporting and publication bias in SC trials related to neurological disorders in Korea.
Project description:The data contained in this article are PubMed search strings and search string builders used to curate breath research manuscripts published from 1995-2016 and the respective number of articles found that satisfied the search requirements for selected categories. Breath sampling represents a non-invasive technique that has gained usefulness for public health, clinical, diagnostic, and environmental exposure assessment applications over the years. This data article includes search strings that were utilized to retrieve publications through the PubMed database for different breath research-related topics that were related to the analysis of exhaled breath, exhaled breath condensate (EBC), and exhaled breath aerosol (EBA) as well as the analysis of cellular headspace. Manuscripts were curated for topics including EBC, EBA, Direct MS, GC-MS, LC-MS, alcohol, and sensors. A summary of the number of papers published per year for the data retrieved using each of the search strings is also included. These data can be utilized to discern trends in the number of breath research publications in each of the different topics over time. A supplementary Appendix A containing the titles, author lists, journal names, publication dates, PMID numbers, and EntrezUID numbers for each of the journal articles curated using the finalized search strings for the seven breath research-related topics can also be found within this article. The selected manuscripts can be used to explore the impact that breath research has had on expanding the scientific knowledge in each of the investigated topics.
Project description:Unabridged access to drug industry and regulatory trial registers and data reduces reporting bias in systematic reviews and may provide a complete index of a drug's clinical study programme. Currently, there is no public index of the human papillomavirus (HPV) vaccine industry study programmes or a public index of non-industry funded studies.By cross-verification via study programme enquiries to the HPV vaccine manufacturers and regulators and searches of trial registers and journal publication databases, we indexed clinical HPV vaccine studies as a basis to address reporting bias in a systematic review of clinical study reports.We indexed 206 clinical studies: 145 industry and 61 non-industry funded studies. One of the four HPV vaccine manufacturers (GlaxoSmithKline) provided information on its study programme. Most studies were cross-verified from two or more sources (160/206, 78%) and listed on regulatory or industry trial registers or journal publication databases (195/206, 95%)-in particular, on ClinicalTrials.gov (176/195, 90%). However, study results were only posted for about half of the completed studies on ClinicalTrials.gov (71/147, 48%). Two thirds of the industry studies had a study programme ID, manufacturer specific ID, and national clinical trial (NCT) ID (91/145, 63%). Journal publications were available in journal publication databases (the Cochrane Collaboration's Central Register of Controlled Trials, Google Scholar and PubMed) for two thirds of the completed studies (92/149, 62%).We believe we came close to indexing complete HPV vaccine study programmes, but only one of the four manufacturers provided information for our index and a fifth of the index could not be cross-verified. However, we indexed larger study programmes than those listed by major regulators (i.e., the EMA and FDA that based their HPV vaccine approvals on only half of the available trials). To reduce reporting bias in systematic reviews, we advocate the registration and publication of all studies and data in the public domain.
Project description:OBJECTIVE:Appendicitis is considered the most frequent surgical emergency in children. While the management of paediatric appendicitis is evolving, the precise amount of unpublished completed trials, potentially introducing bias into meta-analyses, is unknown. Controversial issues include the appropriate choice of surgical procedures, criteria for diagnosis of appendicitis, the role of antibiotic treatment and pain management. Selective reporting may introduce bias into evidence-based clinical decision-making, and the current, precise extent of unpublished results in paediatric appendicitis is unknown. We therefore assessed the publication status of completed clinical studies involving children registered on ClinicalTrials.gov. DESIGN:Cross sectional analysis. STrengthening the Reporting of OBservational studies in Epidemiology criteria were applied for design and analysis. SETTING AND PARTICIPANTS:ClinicalTrials.gov was queried for completed studies which were matched to publications on ClinicalTrials.gov, PubMed or Google Scholar. If no publication could be identified, principal investigators were contacted. INTERVENTIONS/EXPOSURE:Observational analysis. PRIMARY AND SECONDARY OUTCOME MEASURES:The proportion of published and unpublished studies was calculated. Subgroup analysis included studies on surgical procedures, diagnosis, antibiotic treatment and pain management. RESULTS:Out of n=52 completed clinical studies involving children with appendicitis, n=33 (63%) were published and n=19 (37%) were unpublished. Eighty-three per cent (n=43/52) of clinical trials assessed the above-listed controversial issues. Diagnostic studies were most rigorously published (91% of trials reported), data on surgical procedures, antibiotic and pain management were less transparent. Sixty-six per cent of interventional studies and 60% of randomised studies were published. Median time-to-publication, for example, the delay between completion of the trial until public availability of the results was 24 (IQR 12-36), range 2-92 months. CONCLUSION:Despite the importance of appendicitis in clinical practice for the paediatric surgeon, there remains scientific uncertainty due to unpublished clinical trial results with room for improvement in the future. These data are helpful in framing the shifting paradigms in paediatric appendicitis because it adds transparency to the debate.
Project description:Objective:Several publication databases now index the associated funding agency and grant number metadata with their publication records. Librarians who are familiar with the particulars of these databases can assist investigators and administrators with data gathering for publication summaries and metrics required for renewals of and progress reports for National Institutes of Health (NIH) grants. Methods:Publication lists were pulled from three main indexers of publication-associated funding information (NIH RePORTER, PubMed, and Web of Science), using iterative search strategies. All discovered variations for the cited grant number of interest were recorded and tested. Publication lists were compared for overall coverage. Results:A total of 986 publications citing the single grant number of interest were returned from the given time frame: 920 were found in PubMed, 860 in NIH RePORTER, and 787 in Web of Science. Web of Science offered the highest percentage of publications that were not found in the other 2 sources (n=63). Analysis of publication funding acknowledgments uncovered 21 variations of the specific NIH award of interest that were used to report funding support. Conclusions:This study shows that while PubMed returns the most robust list of publications, variations in the format of reported funding support and indexing practices meant no one resource was sufficient to capture all publications that cited a given NIH project grant number. Librarians looking to help build grant-specific publication lists will need to use multiple resources and be aware of the most frequently reported grant variations to identify a comprehensive list of supported publications.
Project description:OBJECTIVES:To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. DESIGN:Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. DATA SOURCES:Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. OUTCOME MEASURES:Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. RESULTS:The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. CONCLUSIONS:Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies' transparency records and recognise exemplary companies may encourage further progress.
Project description:BACKGROUND:Clinical trial transparency is important to participants, trialists, publishers, and regulators, and there have been recent major policy changes by the pharmaceutical industry regarding clinical study data sharing. However, it is unknown if these changes are enabling independent researchers to access participant-level data from prominent contemporary clinical trials sponsored by the pharmaceutical industry 2 years after publication of the primary results. MAIN TEXT:PubMed and ClinicalTrials.gov were searched to identify clinical trials of medicines sponsored by the pharmaceutical industry and first published between 1 July 2015 and 31 December 2015 in the top 10 general and internal medical journals by impact factor. For each clinical trial, the eligibility of independent researchers to request participant-level data was identified via the sponsor having a data sharing policy/process and a positive response to an enquiry. Fifty-six publications reporting on 61 industry-sponsored clinical trials were identified, of which 32 (52%) had a public data sharing policy/process and 9 (15%) were confirmed eligible for data sharing. Industry sponsors within the top 25 by global sales were more likely to have a data sharing policy (93% vs 10%), and there was a trend towards increased data sharing eligibility (23% vs 4%). Twenty-six studies were explicitly confirmed as ineligible for data sharing. The two most common data sharing policy conditions that prevented sharing of data for published results were the exclusion of studies that had ongoing follow-up of the published results and the exclusion of studies of medicines that have not yet achieved regulatory approval in the USA and the European Union. CONCLUSIONS:Fifteen percent of the sampled clinical trials were available for data sharing 2 years after publication of primary results of the trial. Key issues limiting data sharing include a large proportion of industry sponsors who do not have a data sharing policy/process, and data sharing policy conditions that exclude access on the basis of ongoing follow-up and regulatory activity.