Reporting Discrepancies Between the ClinicalTrials.gov Results Database and Peer-Reviewed Publications.
ABSTRACT ClinicalTrials.gov requires reporting of result summaries for many drug and device trials.
To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature.
ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases.
10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups.
One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified.
Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication.
Small sample that included earliest results posted to the database.
Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication.
Agency for Healthcare Research and Quality.
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ABSTRACT: To assess whether journals are more likely to reject manuscripts with differences between information in registries and articles. We compared differences by sponsorship and assessed whether selective reporting favored publication of significant outcomes.Study design and settingDrug trials submitted to eight journals (January 2010-April 2012) were included. Publication status, primary outcomes, enrollment, and sponsorship were extracted. Primary outcomes and enrollment in registries and registration timing were reviewed. Prospective registration included registration before study start. Consistency between registered and reported information was evaluated.ResultsFor 226 submitted manuscripts, primary outcomes were specified in both article and registry. 66/226 (29.2%) had primary outcome differences; 14/66 manuscripts with differences (21.2%) and 46/160 without differences (28.8%) were accepted. 50 manuscripts (22.4%) had sample size differences; 10/50 with differences (20.0%) and 49/173 without differences (28.3%) were accepted. Industry-sponsored trials had less differences and were more often prospectively registered. After adjustment for sponsorship, differences and/or retrospective registration were not associated with decreased chance of acceptance (OR, 0.56; 95% CI, 0.27-1.13). Primary outcome differences favored significant outcomes in 49% of manuscripts.Conclusion Differences between registered and reported information are not decisive for rejection. Editors should assess consistency between registries and articles to address selective reporting.Journal of Clinical Epidemiology 11/2014; · 5.48 Impact Factor
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ABSTRACT: Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies. The first section by Drs. Rosen and Myerburg is an independent review that analyzes the basic science and translational strategies supporting the rapid advance of stem cell technology to the clinic, the philosophies behind them, trial designs, and means for going forward that may impact favorably on progress. The second and third sections were collected as responses to the initial section of this review. The commentary by Drs. Francis and Cole discusses the review by Drs. Rosen and Myerburg and details how trial outcomes can be affected by noise, poor trial design (particularly the absence of blinding), and normal human tendencies toward optimism and denial. The final, independent paper by Dr. Marbán takes a different perspective concerning the potential for positive impact of stem cell research applied to heart disease and future prospects for its clinical application. (Compiled by the JACC editors)Journal of the American College of Cardiology 09/2014; 64(9):922–937. · 15.34 Impact Factor
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ABSTRACT: Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use.Clinical and Experimental Vaccine Research. 01/2015; 4(1):23-45.