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The global burden of osteoporotic fractures is associated with significant morbidity, mortality, and healthcare costs. We examined the ClinicalTrials.gov database to determine whether recently registered clinical trials addressed prevention and treatment in those at high risk for fracture. A dataset of 96,346 trials registered in ClinicalTrials.gov was downloaded on September 27, 2010. At the time of the dataset download, 40,970 interventional trials had been registered since October 1, 2007.doi:10.1371/journal.pone.0156068 pmid:27191848 pmcid:PMC4871563 fatcat:6tz2gehxlnf4zgfpfrjm56qisa
more »... e osteoporosis subset comprised 239 interventional trials (0.6%). Those trials evaluating orthopedic procedures were excluded. The primary purpose was treatment in 67.0%, prevention in 20.1%, supportive care in 5.8%, diagnostic in 2.2%, basic science in 3.1%, health services research in 0.9%, and screening in 0.9%. The majority of studies (61.1%) included drug-related interventions. Most trials (56.9%) enrolled only women, 38.9% of trials were open to both men and women, and 4.2% enrolled only men. Roughly one fifth (19.7%) of trials excluded research participants older than 65 years, and 33.5% of trials excluded those older than 75 years. The funding sources were industry in 51.0%, the National Institutes of Health in 6.3%, and other in 42.7%. We found that most osteoporosis-related trials registered from October 2007 through September 2010 examined the efficacy and safety of drug treatment, and fewer trials examined prevention and non-drug interventions. Trials of interventions that are not required to be registered in ClinicalTrials.gov may be underrepresented. Few trials are specifically studying osteoporosis in men and older adults. Recently registered osteoporosis trials may not sufficiently address fracture prevention.
The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. Methods Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicabledoi:10.1056/nejmsa1409364 pmid:25760355 pmcid:PMC4508873 fatcat:lk35eorprvdh5kxgcppjy7xdye
more »... ical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. Results From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industryfunded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. Conclusions Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.) The New England Journal of Medicine Downloaded from nejm.org on March 12, 2015. For personal use only. No other uses without permission.
Background-ClinicalTrials.gov is an NIH-sponsored registry of federally and privately funded trials. We sought to determine fundamental characteristics of registered pediatric cardiovascular trials (PCVTs). Methods-A data set including 68134 interventional clinical trials was downloaded from ClinicalTrials.gov and entered into a relational database. Aggregate data from PCVTs were compared with other trial specialties. Multivariable logistic regression was used to evaluate factors associateddoi:10.1016/j.ahj.2014.02.002 pmid:24890544 pmcid:PMC4044612 fatcat:lvhjhmuygrauvp6funitqmgpvm
more »... improved trial quality metrics including blinding and randomization. Results-Between 7/01/2005 and 9/27/2010, 5035 (7%) registered trials targeted pediatric populations, including 213 PCVTs (4.2%), 1176 pediatric infectious disease trials (23%), 664 pediatric mental health trials (13%) and 346 pediatric hematology/oncology trials (7%). Median (IQR) PCVT enrollment was 65 subjects (36-186) and median study duration was 2.3 years (1.3-3.7). The most common PCVTs targeted acquired diseases including hypertension (n=41, 14%), obesity (n=26, 9%), pulmonary hypertension (n=25, 9%) and dyslipidemia (n=19, 7%). Important factors associated with improved quality metrics included: NIH as opposed to industry funding (OR=1.9, p<0.0001); trial location (trials with both U.S.and foreign enrollment vs. trials with US only or foreign only enrollment, p=0.02) and trials restricted to younger children as opposed to trials including adolescents (OR=1.4, p<0.0001). Conclusion-PCVTs represent a small proportion of clinical trials relative to other pediatric sub-specialties. Most PCVTs tend to parallel adult morbidities while there is a relative paucity of trials focused on congenital heart disease. These data may be useful to stakeholders in informing decisions regarding the conduct of PCVTs, and to provide insight into mechanisms to advance PCVT infrastructure.
Registration of interventional trials of Food and Drug Administration-regulated drug and biological products and devices became a legal requirement in 2007; the vast majority of these trials are registered in ClinicalTrials.gov. An analysis of ClinicalTrials.gov offers an opportunity to define the clinical research landscape; here we analyze 10 years of infectious disease (ID) clinical trial research. Beginning with 166 415 interventional trials registered in ClinicalTrials.gov from 2007-2017,doi:10.1093/ofid/ofz189 pmid:31276007 pmcid:PMC6598302 fatcat:65sbz5ujk5durmfyhpypaqawpq
more »... D trials were selected by study conditions and interventions. Relevance to ID was confirmed through manual review, resulting in 13 707 ID trials and 152 708 non-ID trials. ID-related trials represented 6.9%-9.9% of all trials with no significant trend over time. ID trials tended to be more focused on treatment and prevention, with a focus on testing drugs, biologics, and vaccines. ID trials tended to be large, randomized, and nonblinded with a greater degree of international enrollment. Industry was the primary funding source for 45.2% of ID trials. Compared with the global burden of disease, human immunodeficiency virus/AIDS and hepatitis C trials were overrepresented, and lower respiratory tract infection trials were underrepresented. Hepatitis C trials fluctuated, keeping with a wave of new drug development. Influenza vaccine trials peaked during the 2009 H1N1 swine influenza outbreak. This study presents the most comprehensive characterization of ID clinical trials over the past decade. These results help define how clinical research aligns with clinical need. Temporal trends reflect changes in disease epidemiology and the impact of scientific discovery and market forces. Periodic review of ID clinical trials can help identify gaps and serve as a mechanism to realign resources.
Cardiovascular medicine is widely regarded as a vanguard for evidence-based drug and technology development. Our goal was to describe the cardiovascular clinical research portfolio from ClinicalTrials.gov. We identified 40 970 clinical research studies registered between 2007 and 2010 in which patients received diagnostic, therapeutic, or other interventions per protocol. By annotating 18 491 descriptors from the National Library of Medicine's Medical Subject Heading thesaurus and 1220doi:10.1161/jaha.113.000009 pmid:24072529 pmcid:PMC3835214 fatcat:y5df5qo6bbgv3lmpohm37ou6je
more »... terms to select those relevant to cardiovascular disease, we identified studies that related to the diagnosis, treatment, or prevention of diseases of the heart and peripheral arteries in adults (n = 2325 [66%] included from review of 3503 potential studies). The study intervention involved a drug in 44.6%, a device or procedure in 39.3%, behavioral intervention in 8.1%, and biological or genetic interventions in 3.0% of the trials. More than half of the trials were postmarket approval (phase 4, 25.6%) or not part of drug development (no phase, 34.5%). Nearly half of all studies (46.3%) anticipated enrolling 100 patients or fewer. The majority of studies assessed biomarkers or surrogate outcomes, with just 31.8% reporting a clinical event as a primary outcome. Cardiovascular studies registered on ClinicalTrials.gov span a range of study designs. Data have limited verification or standardization and require manual processes to describe and categorize studies. The preponderance of small and late-phase studies raises questions regarding the strength of evidence likely to be generated by the current portfolio and the potential efficiency to be gained by more research consolidation.
Objectives-To investigate whether tirofiban would have been non-inferior to abciximab had the trial completed enrollment, and we place the termination of this trial in a broader research ethics context. Background-TENACITY was terminated by the sponsor for financial reasons. At the time, event rates for the 2 treatment arms were unknown. Methods-TENACITY was designed to compare tirofiban with abciximab in approximately 8000 patients; however, enrollment was terminated after 383 (4.8%) patients.doi:10.1111/j.1540-8183.2013.12020.x pmid:23379785 pmcid:PMC4156852 fatcat:t5f4fqq5vbe43hhr3auydh5iua
more »... The primary endpoint was a composite of 30-day death, myocardial infarction, and urgent target vessel revascularization. Non-inferiority was defined as the likelihood that tirofiban would preserve at least 50% of the ability of abciximab to reduce the primary endpoint at 30 days, based on abciximab's demonstrated ability to reduce such events by 43% (relative risk, 0.573; 95% confidence interval [CI], 0.507-0.648; P<0.001). To determine the probability of non-inferiority given the patients already enrolled, a Bayesian approach was used. Results- The primary composite endpoint occurred in 8.8% of patients randomized to abciximab vs. 6.9% receiving high-bolus-dose tirofiban (odds ratio, 0.77; 95% CI, 0.37-1.64). The estimated conditional power for the test that tirofiban would be non-inferior to abciximab if all patients been enrolled is 93.7%. Using the estimated predictive power method, the likelihood was 84.8%. Conclusions-TENACITY was well-powered to identify non-inferiority with tirofiban vs. abciximab, and the patients enrolled strengthened the probability that this would have been the outcome had the trial been completed. When a clinical trial is terminated solely for financial reasons, it is incumbent upon the sponsor to provide proper patient follow-up and publication of the findings.
There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. Methods: We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trialsdoi:10.1371/journal.pone.0077086 pmid:24146958 pmcid:PMC3797691 fatcat:oh3tt54pmjforok74j64xdxa4q
more »... and 37,400 non-ID trials for analysis. Results: The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. Conclusions: This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.
Lee, interpretation of data, drafting and review of manuscript, approval; Karen Chiswell, acquisition of data, analysis, drafting of manuscript and approval. ...doi:10.1177/0194599813506545 pmid:24107478 pmcid:PMC4121965 fatcat:xsnbx7tz6fcmzneukzaxtjxya4
The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular.doi:10.1371/journal.pone.0033677 pmid:22438982 pmcid:PMC3306288 fatcat:yhyhlevp5nepzmo47oon4zlgvy
more »... g usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. Methods/Principal Results: The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. Conclusions/Significance: The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups.
Sudden infant death syndrome (SIDS) is the sudden, unexplained death of infants <1 year old. SIDS remains a leading cause of death in US infants. We aim to identify associations between SIDS and race/ethnicity, birth weight/gestational age, and socioeconomic/environmental factors in North Carolina (NC) to help identify infants at risk for SIDS.Methods and Results: In this IRB-approved study, infant mortality 2007–2016 and death certificate-linked natality 2007–2014 were obtained from the NCdoi:10.3389/fped.2021.770803 pmid:34956982 pmcid:PMC8703192 fatcat:7iu4f4e4pvblzljxbjeu7hluqe
more »... epartment of Health and Human Services. General, NC natality statistics 2007–2016 were obtained from CDC Wonder. Association between SIDS/total infant death and covariates (below) were calculated. Total infant mortality decreased 2007–2016 by an average of 14 deaths/100,000 live births per year, while SIDS incidence remained constant. Risk ratios of SIDS/total infant deaths, standardized to Non-Hispanic White, were 1.76/2.41 for Non-Hispanic Black and 0.49/0.97 for Hispanic infants. Increased SIDS risk was significantly and independently associated with male infant sex, Non-Hispanic Black maternal race/ethnicity, young maternal age, low prenatal care, gestational age <39 weeks, birthweight <2500 g, low maternal education, and maternal tobacco use (p < 0.01). Maternal previous children now deceased also trended toward association with increased SIDS risk.Conclusions: A thorough SIDS risk assessment should include maternal, socioeconomic, and environmental risk factors as these are associated with SIDS in our population.
Aims-The impact of refractory angina pectoris (AP) in patients with ischaemic cardiomyopathy (ICM) is unknown. We investigated the characteristics and outcomes of ICM patients with persistent AP following cardiac catheterization. Methods and results-Patients who underwent coronary angiography at Duke from 2000 to 2009 with an EF <40% and ICM with persistent AP were compared with similar patients without persistent AP. Persistent AP was defined by patient report of ischaemic symptoms within 1doi:10.1002/ejhf.130 pmid:24975128 pmcid:PMC5702887 fatcat:wfi4uhkmwvfflkplzdff7obkdm
more »... r of index catheterization. Time-to-event was examined using Kaplan-Meier or cumulative incidence and Cox proportional hazards modelling methods for death/myocardial infarction (MI)/ revascularization [i.e. major adverse cardiac events (MACE)], death/MI, death, and cardiovascular death/hospitalization. Of 965 ICM patients, 298 (31%) had persistent AP. These patients were younger and had more previous revascularization than patients without persistent AP. Both groups had high use of aspirin, beta-blockers, ACE inhibitors, and statins, but modest nitrate use. Over a median follow-up of > 5 years, patients with persistent AP had increased rates of MACE, and cardiovascular death/hospitalization compared with patients without persistent AP [5-year cumulative event rates of 53% vs. 46% (p = 0.013) and 73% vs. 60% (p < 0.0001), respectively], but similar rates of death (p = 0.59) and death/MI (p = 0.50). After multivariable adjustment, persistent AP remained associated with increased MACE [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.08-1.57], and cardiovascular death/hospitalization (HR 1.36; 95% CI 1.14-1.62). Conclusion-Persistent AP is common despite medical therapy in patients with ICM and is independently associated with increased long-term MACE and rehospitalization. Future prospective studies of persistent AP in ICM patients are warranted.
Background-Well-designed trials are of paramount importance in improving the delivery of care to patients with kidney disease. However, it remains unknown whether contemporary clinical trials within nephrology are of sufficient quality and quantity to meet this need. Study Design-Systematic review. Setting & Population-Studies registered with ClinicalTrials.gov. Selection Criteria for Studies-Interventional (i.e., non-observational) studies (both randomized and nonrandomized) registered betweendoi:10.1053/j.ajkd.2013.10.043 pmid:24315119 pmcid:PMC3988265 fatcat:f4qenoduuzdz3hwciugvtjjjdu
more »... October 2007 and September 2010 were included for analysis. Studies were independently reviewed by physicians and classified by clinical specialty. Predictor-Nephrology versus cardiology versus other trials. Outcomes-Select clinical trial characteristics. Results-Of the 40,970 trials overall, 1054 (2.6%) were classified as nephrology. The majority of nephrology trials were for treatment (75.4%) or prevention (15.7%), with very few diagnostic, screening, or health services research studies. Most nephrology trials were randomized (72.3%), including 24.9% that included a single study group, 64.0% that included parallel groups, and 9.4% that were crossover trials. Nephrology trials, compared with 2264 cardiology trials (5.5% overall), were more likely to be smaller (64.5% versus 48.0% enrolling ≤100 patients), phase I-II (29.0%
Todd, White, Chiswell, et al.: Pulmonary, Critical Care, and Sleep Medicine Trials ... Karen Alexander and Dr. David Kong. †Morbidity estimates according to the Centers for Disease Control summary health statistics for U.S. adults: National Health Interview Survey, 2011 (19) . ...doi:10.1513/annalsats.201305-111oc pmid:23987571 pmcid:PMC3882749 fatcat:jf7nsodhozfopb3yndfz7klvcm
Objectives This study sought to determine if there is an association between bleed location and clinical outcomes in acute coronary syndromes (ACS) patients. Background The prognostic significance of bleeding location among ACS patients undergoing cardiac catheterization is not well known. Methods We analyzed in-hospital bleeding events among 9,978 patients randomized in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors)doi:10.1016/j.jcin.2013.03.010 pmid:23866183 pmcid:PMC3884698 fatcat:du22bo3rhze4vo4j262swz4dj4
more »... Bleeding events were categorized by location as access site, systemic, surgical, or superficial, and severity was graded using the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definition. We assessed the association of each bleeding location and severity with 6-month risk of death or myocardial infarction using a multicovariate-adjusted Cox proportional hazard model. Results A total of 4,900 bleeding events were identified among 3,694 ACS patients with in-hospital bleeding. Among 4,679 GUSTO mild/moderate bleeding events, only surgical and systemic bleeds were associated with an increased risk of 6-month death or myocardial infarction (adjusted hazard ratio [HR]: 2.52 [95% confidence interval (CI): 2.16 to 2.94, and 1.40 [95% CI: 1.16 to 1.69], respectively). Mild/moderate superficial and access-site bleeds were not associated with downstream risk (adjusted HR: 1.17 [95% CI: 0.97 to 1.40], and 0.96 [95% CI: 0.82 to 1.12], respectively). Among 221 GUSTO severe bleeds, surgical bleeds were associated with the highest risk (HR: 5.27 [95% CI: 3.80 to 7.29]), followed by systemic (HR: 4.48 [95% CI: 2.98 to 6.72]), and finally access-site bleeds (HR: 3.57 [95% CI: 2.35 to 5.40]). Conclusions Among ACS patients who develop in-hospital bleeding, systemic and surgical bleeding are associated with the highest risks of adverse outcomes regardless of bleeding severity. Although the most frequent among bleeds, GUSTO mild/moderate access-site bleeding is not associated with increased risk. These data underscore the importance of strategies to minimize overall bleeding risk beyond vascular access site management. (J Am Coll Cardiol Intv 2013;6:709-17) ª
Aim: The authors assessed the comparative effectiveness of torsemide versus furosemide in the PROTECT trial. Methods: The authors assessed the relationship between loop diuretic at discharge and death or cardiovascular/renal hospitalization within 30 days, and death through 150 days postdischarge using inverse probability weighting. Results: Out of 1004 patients, 83.5% received furosemide and 16.5% torsemide. Torsemide patients had higher blood urea nitrogen, and more in-hospital worseningdoi:10.2217/fca.15.56 pmid:26403536 pmcid:PMC5558519 fatcat:ku62m6eon5af3cdo5jj3sxthmm
more »... failure. Following adjustment, torsemide was associated with similar 30-day outcomes compared with furosemide (p = 0.93), but remained associated with increased 150-day death (hazard ratio: 2.26; 95% CI: 1.40-3.66; p < 0.001). Conclusion: Patients treated with torsemide had features of greater disease severity, similar 30-day outcomes but increased 150-day mortality. Prospective randomized trials are needed to investigate the effect of torsemide versus furosemide. KEYWORDS For reprint orders, please contact: email@example.com future science group RESEaRch aRticlE Mentz, Velazquez, Metra et al.
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