Discrepancies in the Registries of Diet vs Drug Trials.
Ontology highlight
ABSTRACT:
SUBMITTER: Ludwig DS
PROVIDER: S-EPMC6902790 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Discrepancies in the Registries of Diet vs Drug Trials.
Ludwig David S DS Ebbeling Cara B CB Heymsfield Steven B SB
JAMA network open 20191101 11
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Project description:Nephrology has conducted few high-quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are overarching process issues that affect the conduct of all clinical trials, but there are also some specialty-specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases.
| S-EPMC5142054 | biostudies-literature
Project description:BackgroundComplete and unbiased reporting of clinical trial results is essential for evaluating medical advances, yet publication bias and reporting discrepancies in research on the clinical application of artificial intelligence (AI) remain unknown.MethodsWe conducted a comprehensive search of research publications and clinical trial registries focused on the application of AI in healthcare. Our search included publications in Dimensions.ai and pre-registered records from ClinicalTrials.gov and the EU Clinical Trials Registry before 31 December 2023. We linked registered trials to their corresponding publications, analysed the registration, reporting and different dissemination patterns of results, identified discrepancies between clinical trial registries and published literature, and assessed the use of these results in secondary research.FindingsWe identified 28,248 publications related to the use of AI in clinical settings and found 1863 publications that included a clinical trial registration ID. The clinical trial registry search identified 3710 trials evaluating the use of AI in clinical settings, of which 1106 trials are completed, yet only 101 trials have published results. By linking the trials to their corresponding publications, we found that 26 trials had results available from both registries and publications. There were more results in trial registries than in articles, but researchers showed a clear preference for rapid dissemination of results through peer-reviewed articles (37.6% published within one year) over trial registries (15.8%). Discrepancies and omissions of results were common, and no complete agreement was observed between the two sources. Selective reporting of publications occurred in 53.6% of cases, and the underestimation of the incidence of adverse events is alarming.InterpretationThis research uncovers concerns with the registration and reporting of AI clinical trial results. While trial registries and publications serve distinct yet complementary roles in disseminating research findings, discrepancies between them may undermine the reliability of the evidence. We emphasise adherence to guidelines that promote transparency and standardisation of reporting, especially for investigator-initiated trials (IITs).FundingThe authors declare no source of funding.
| S-EPMC11831125 | biostudies-literature
Project description:PurposeKnowledge of the benefits and risks of new drugs is incomplete at the time of marketing approval. Registries offer the possibility for additional, post-approval, data collection. For all new drugs, which were approved in the European Union between 2007 and 2010, we reviewed the frequency, the type, and the reason for requiring a registry.MethodsThe European Public Assessment Reports, published on the website of the European Medicine Agency, were reviewed for drugs approved by the Committee for Medicinal Products for Human Use. We searched for key characteristics of these drugs, including therapeutic area (ATC1 level), level of innovation (the score is an algorithm based on availability of treatment and therapeutic effect), and procedural characteristics. In addition, we identified if these registries were defined by disease (disease registry) or exposure to a single drug (drug registry).ResultsOut of 116 new drugs approved in the predefined period, for 43 (37%), 1 to 6 registry studies were identified, with a total of 73 registries. Of these 46 were disease registries and 27 (single) drug registries. For 9 drugs, the registry was a specific obligation imposed by the regulators. The level of innovation and the orphan status of the drugs were determinants positively predicting post-approval registries (OR 10.3 [95% CI 1.0-103.9] and OR 2.8 [95% CI 1.0-7.5], respectively).ConclusionsThe majority of registries required by regulators are existing disease registries. Registries are an important and frequently used tool for post-approval data collection for orphan and innovative drugs.
| S-EPMC5725674 | biostudies-literature
Project description:Participant registries are repositories of individuals who have expressed willingness to learn about studies for which they may be eligible. Registries are increasingly being utilized to improve recruitment to preclinical Alzheimer's disease (AD) clinical trials, which require large screening efforts to identify adequate numbers of participants who meet enrollment criteria. Recruiting to preclinical AD trials from registries is made more efficient through registry collection of data that permits exclusion of those who will not be eligible and identifies individuals most likely to qualify for trials. Such data could include self-reported disease family history or other risk factors, but could also include cognitive, genetic, or biomarker testing outcomes. Few data are available to guide investigators overseeing registries and important ethical questions are likely to arise related to their conduct, especially in registries collecting AD risk information. This article outlines three areas of consideration for registry investigators: informed consent, disclosure, and sponsorship.
| S-EPMC5399544 | biostudies-literature
Project description:BackgroundPrecision medicine has been adopted in a range of clinical settings where omics data have led to greater characterisation of disease and stratification of patients into subcategories of phenotypes and pathologies. However, in orthopaedics, precision medicine lags behind other disciplines such as cancer. Joint registries have now amassed a huge body of data pertaining to implant performance which can be broken down into performance statistics for different material types in different cohorts of patients. The National Joint Registry of England, Wales and Northern Ireland (NJR) is now one of the largest datasets available. Other registries such as those from Sweden and Australia however contain longer follow-up. Together, these registries can provide a wealth of informative for the orthopaedics community when considering which implant to give to any particular patient.Questions/purposesWe aim to explore the benefits of combining multiple large data streams including joint registries, published data on osteoarthritis (OA) pathogenesis and pathology and data concerning performance of each implant material combination in terms of biocompatibility. We believe that this analysis will provide a comprehensive overview of implant performance hopefully aiding surgeons in making more informed choices about which implant should be used in which patient.MethodsData from three joint registries were combined with established literature to highlight the heterogeneity of OA disease and the different clinical outcomes following arthroplasty with a range of material types.ResultsThis review confirms that joint registries are unable to consider differences in arthritis presentation or underlying drivers of pathology. OA is now recognised to present with varying pathology with differing morbidity in different patient populations. Equally, just as OA is a heterogeneous disease, there are disparate responses to wear debris from different material combinations used in joint replacement surgery. This has been highlighted by recent high-profile scrutiny of early failure of metal-on-metal total hip replacement (THR) implants.ConclusionsBringing together data from joint registries, biomarker analysis, phenotyping of OA patients and knowledge of how different patients respond to implant debris will lead to a truly personalised approach to treating OA patients, ensuring that the correct implant is given to the correct patient at the correct time.
| S-EPMC5264580 | biostudies-literature
Project description:Background and purpose - Patellofemoral arthroplasty (PFA) has been debated since early studies showed poor implant survival. Recent studies show better results. This review reports failure modes for PFA and investigates differences in data reported from registries and clinical studies. Additionally, we report differences in failure modes among implant designs. Methods - A systematic search was performed in September 2018. All studies and registers describing failure modes of PFA were included and implant design was noted for each revision. Results - This review includes 1,299 revisions of a primary PFA reported in 47 clinical studies and 3 registers. The failure modes were: 42% OA progression, 16% pain, 13% aseptic loosening, 12% surgical error, 4% wear, 2% infection, 2% broken patellar component, 1% stiffness, 1% fracture, and 7% other. The data from registries and cohort studies differed statistically significantly in 7 out of 12 failure modes. Significant differences were found in several failure modes among implant designs. Interpretation - OA progression is the most common failure mode of PFA. There are significant differences in data on failure modes between registers and protocolled studies, notably for surgical error. The implant design significantly influences several of the failure modes. In conclusion, indication, surgical technique, and implant design are important for a successful PFA, and register-based failure modes should be interpreted with caution.
| S-EPMC6746256 | biostudies-literature
Project description:We examined the use of clinical trials registries in published systematic reviews and meta-analyses from clinical neurology. A review of publications between January 1, 2008 and December 31, 2014 from five neuroscience journals (Annals of Neurology, Brain, Lancet Neurology, Neurology, and The Neuroscientist) was performed to identify eligible systematic reviews. The systematic reviews comprising the final sample were independently appraised to determine if clinical trials registries had been included as part of the search process. Studies acknowledging the use of a trials registry were further examined to determine whether trial data had been incorporated into the analysis. The initial search yielded 194 studies, of which 78 systematic reviews met the selection criteria. Of those, five acknowledged the use of a specific clinical trials registry: four reviewed unpublished trial data and two incorporated unpublished trial data into their results. Based on our sample of systematic reviews, there was no increase in the use of trials registries in systematic review searches over time. Few systematic reviews published in clinical neurology journals included data from relevant clinical trials registries.
| S-EPMC4520588 | biostudies-literature
Project description:BackgroundBiodegradable polymeric coatings have been proposed as a promising strategy to enhance biocompatibility and improve the delayed healing in the vessel. However, the efficacy and safety of biodegradable polymer drug-eluting stents (BP-DES) vs. bare metal stents (BMS) are unknown. The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing the outcomes of BP-DES vs. BMS.Methods and resultsPubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until December 2013, that compared any of approved BP-DES and BMS. Efficacy endpoints were target-vessel revascularization (TVR), target-lesion revascularization (TLR) and in-stent late loss (ISLL). Safety endpoints were death, myocardial infarction (MI), definite stent thrombosis (DST). The meta-analysis included 7 RCTs with 2,409 patients. As compared with BMS, there was a significantly reduced TVR (OR [95% CI] = 0.37 [0.28-0.50]), ISLL (OR [95% CI] = -0.41 [-0.48-0.34]) and TLR (OR [95% CI] = 0.38 [0.27-0.52]) in BP-DES patients. However, there were no difference for safety outcomes between BP-DES and BMS.ConclusionsBP-DES is more effective in reducing ISLL, TVR and TLR, as safe as standard BMS with regard to death, ST and MI. Further large RCTs with long-term follow-up are warranted to better define the relative merits of BP-DES.
| S-EPMC4063774 | biostudies-literature
Project description:Unfolded states of proteins and native states of intrinsically disordered proteins (IDPs) populate heterogeneous conformational ensembles in solution. The average sizes of these heterogeneous systems, quantified by the radius of gyration (RG ), can be measured by small-angle X-ray scattering (SAXS). Another parameter, the mean dye-to-dye distance (RE ) for proteins with fluorescently labeled termini, can be estimated using single-molecule Förster resonance energy transfer (smFRET). A number of studies have reported inconsistencies in inferences drawn from the two sets of measurements for the dimensions of unfolded proteins and IDPs in the absence of chemical denaturants. These differences are typically attributed to the influence of fluorescent labels used in smFRET and to the impact of high concentrations and averaging features of SAXS. By measuring the dimensions of a collection of labeled and unlabeled polypeptides using smFRET and SAXS, we directly assessed the contributions of dyes to the experimental values RG and RE For chemically denatured proteins we obtain mutual consistency in our inferences based on RG and RE , whereas for IDPs under native conditions, we find substantial deviations. Using computations, we show that discrepant inferences are neither due to methodological shortcomings of specific measurements nor due to artifacts of dyes. Instead, our analysis suggests that chemical heterogeneity in heteropolymeric systems leads to a decoupling between RE and RG that is amplified in the absence of denaturants. Therefore, joint assessments of RG and RE combined with measurements of polymer shapes should provide a consistent and complete picture of the underlying ensembles.
| S-EPMC5547626 | biostudies-literature
Project description:ImportanceClinical trial registries are important for gaining an overview of ongoing research efforts and for deterring and identifying publication bias and selective outcome reporting. The reliability of the information in trial registries is uncertain.ObjectiveTo assess the reliability of information across registries for trials with multiple registrations.Evidence reviewFor this systematic review, 360 protocols of randomized clinical trials (RCTs) approved by research ethics committees in Switzerland, the UK, Canada, and Germany in 2012 were evaluated. Clinical trial registries were searched from March to September 2019 for corresponding registrations of these RCTs. For RCTS that were recorded in more than 1 clinical trial registry, key trial characteristics that should be identical among all trial registries (ie, sponsor, funding source, primary outcome, target sample size, trial status, date of first patient enrollment, results available, and main publication indexed) were extracted in duplicate. Agreement between the different trial registries for these key characteristics was analyzed descriptively. Data analyses were conducted from May 1 to November 30, 2020. Representatives from clinical trial registries were interviewed to discuss the study findings between February 1 and March 31, 2021.FindingsThe analysis included 197 RCTs registered in more than 1 trial registry (151 in 2 registries and 46 in 3 registries), with 188 trials in ClinicalTrials.gov, 185 in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), 20 in ISRCTN, and 47 in other registries. The agreement of key information across all registries was as follows: 178 of 197 RCTs (90%; 95% CI, 85%-94%) for sponsor, 18 of 20 (90%; 95% CI, 68%-99%) for funding source (funding was not reported on ClinicalTrials.gov), 154 of 197 (78%; 95% CI, 72%-84%) for primary outcome, 90 of 197 (46%; 95% CI, 39%-53%) for trial status, 122 of 194 (63%; 95% CI, 56%-70%) for target sample size, and 43 of 57 (75%; 95% CI, 62%-86%) for the date of first patient enrollment when the comparison time was increased to 30 days (date of first patient enrollment was not reported on EudraCT). For results availability in trial registries, agreement was 122 of 197 RCTs (62%; 95% CI, 55%-69%) for summary data reported in the registry and 91 of 197 (46%; 95% CI, 39%-53%) for whether a published article with the main results was indexed. Different legal requirements were stated as the main reason for inconsistencies by representatives of clinical trial registries.Conclusions and relevanceIn this systematic review, for a substantial proportion of registered RCTs, information about key trial characteristics was inconsistent across trial registries, raising concerns about the reliability of the information provided in these registries. Further harmonization across clinical trial registries may be necessary to increase their usefulness.
| S-EPMC8561329 | biostudies-literature