BACKGROUND 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 applicable clinical 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 industry-funded 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.

AimsIn symptomatic patients with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) improves patient selection for invasive coronary angiography (ICA) compared with functional testing. The impact of measuring fractional flow reserve by CTA (FFRCT) is unknown.Methods and resultsAt 11 sites, 584 patients with new onset chest pain were prospectively assigned to receive either usual testing (n = 287) or CTA/FFRCT (n = 297). Test interpretation and care decisions were made by the clinical care team. The primary endpoint was the percentage of those with planned ICA in whom no significant obstructive CAD (no stenosis ≥50% by core laboratory quantitative analysis or invasive FFR < 0.80) was found at ICA within 90 days. Secondary endpoints including death, myocardial infarction, and unplanned revascularization were independently and blindly adjudicated. Subjects averaged 61 ± 11 years of age, 40% were female, and the mean pre-test probability of obstructive CAD was 49 ± 17%. Among those with intended ICA (FFRCT-guided = 193; usual care = 187), no obstructive CAD was found at ICA in 24 (12%) in the CTA/FFRCT arm and 137 (73%) in the usual care arm (risk difference 61%, 95% confidence interval 53–69, P< 0.0001), with similar mean cumulative radiation exposure (9.9 vs. 9.4 mSv, P = 0.20). Invasive coronary angiography was cancelled in 61% after receiving CTA/FFRCT results. Among those with intended non-invasive testing, the rates of finding no obstructive CAD at ICA were 13% (CTA/FFRCT) and 6% (usual care; P = 0.95). Clinical event rates within 90 days were low in usual care and CTA/FFRCT arms.ConclusionsComputed tomographic angiography/fractional flow reserve by CTA was a feasible and safe alternative to ICA and was associated with a significantly lower rate of invasive angiography showing no obstructive CAD.

Background— Sex differences in early mortality after myocardial infarction (MI) vary by age. MI with nonobstructive coronary arteries (MINOCA [<50% stenosis]) is more common among younger patients and women, and MINOCA has a better prognosis than MI with obstructive coronary artery disease (MI-CAD). The relationship between age, sex, and obstructive CAD status and outcomes post-MI has not been established. Methods and Results— Adults who underwent coronary angiography for acute ST-segment–elevation and non–ST-segment–elevation MI in the National Cardiovascular Data Registry ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines) from 2007 to 2014 were identified. Patients with cardiac arrest, thrombolytic therapy, prior revascularization, or missing demographic or angiographic data were excluded. The primary outcome was all-cause, in-hospital mortality. Secondary outcomes included major adverse cardiovascular events. Demographics, clinical history, presentation, and in-hospital treatments were compared by sex and CAD status (MI-CAD or MINOCA). Mortality and major adverse cardiovascular outcomes were analyzed by age, sex, and CAD status. Among 322 523 patients with MI, MINOCA occurred in 18 918 (5.9%). MINOCA was more common in women than men (10.5% versus 3.4%; P <0.0001), and women had higher mortality than men overall (3.6% versus 2.4%; P <0.0001). In-hospital mortality was lower after MINOCA than MI-CAD (1.1% versus 2.9%; P <0.0001). Among patients with MI-CAD, women had higher mortality than men (3.9% versus 2.4%; P <0.0001) while no sex difference in mortality was observed with MINOCA (1.1% versus 1.0%; P =0.84). The higher risk of post-MI death among women with MI-CAD was most pronounced at younger ages. Conclusions— MINOCA was associated with lower mortality than MI-CAD. Higher risk of post-MI death among women in comparison to men was restricted to patients with MI-CAD.

In patients with stable chest pain and planned invasive coronary angiography, care guided by CTA and selective FFRCT was associated with equivalent clinical outcomes and QOL, and lower costs, compared with usual care over 1-year follow-up. (The PLATFORM Study: Prospective LongitudinAl Trial of FFRct: Outcome and Resource IMpacts [PLATFORM]; NCT01943903).

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BackgroundThe 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. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource.Methods/Principal ResultsThe 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/SignificanceThe 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.

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 between 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% versus 19.7%), and unblinded (66.2% versus 53.3%; P<0.05 for all). Nephrology trials were also more likely than cardiology trials to include a drug intervention (72.4% versus 41.9%) and were less likely to report having a data monitoring committee (40.3% versus 48.5%; P<0.05 for all). Finally, there were few trials funded by the National Institutes of Health (3.3%, nephrology; 4.2%, cardiology). Limitations Does not include all trials performed worldwide, and frequent categorization of funding source as university may underestimate NIH support. Conclusions Critical differences remain between clinical trials in nephrology and other specialties. Improving care for patients with kidney disease will require a concerted effort to increase the scope, quality, and quantity of clinical trials within nephrology.

AimsChronic obstructive pulmonary disease (COPD) is common in heart failure (HF) patients, yet the population is poorly characterized and associated with conflicting outcomes data. We aimed to evaluate the clinical characteristics and outcomes of HF patients with systolic dysfunction and COPD in a large acute HF registry. Methods and results OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in HospitalizedPatients with Heart Failure) was a performance-improvement registry of patients hospitalized with HF (n ¼ 48 612), which included a pre-specified subgroup of patients (n ¼ 5,701) with 60-to 90-day follow-up. We performed a retrospective analysis of the clinical characteristics and outcomes (length of stay, and in-hospital and 60-day mortality) of patients with systolic dysfunction according to baseline COPD status. COPD was present in 25% of the patients. These patients had more co-morbidities compared with patients without COPD. They were less likely to receive a beta-blocker or angiotensin-converting enzyme inhibitor during hospitalization and at discharge (P , 0.001). COPD was associated with an increased median length of stay [5 days (interquartile range 3-8) vs. 4 days (interquartile range 3-7), P , 0.0001] and increased in-hospital all-cause and non-cardiovascular (CV) mortality, with rates of 4.5% vs. 3.7% (P ¼ 0.01) and 1.0% vs. 0.6% (P ¼ 0.01), respectively, for the two endpoints, but similar 60-day mortality (6.2% vs. 6.0%, P ¼ 0.28). After risk adjustment, the in-hospital non-CV mortality remained increased (odds ratio 1.65, 95% confidence interval 1.12-2.41; P ¼ 0.01). ConclusionThe presence of COPD in HF patients with systolic dysfunction is associated with an increased burden of co-morbidities, lower use of evidence-based HF medications, longer hospitalizations, and increased in-hospital non-CV mortality, but similar post-discharge mortality.--