EMBARGOED FOR EARLY RELEASE: 11 A.M. (CT) MONDAY, NOVEMBER 5, 2012
Use of Corticosteroid During Cardiac Surgery Does Not Appear to Improve Outcomes
Jan M. Dieleman, M.D., of the University Medical Center, Utrecht, the Netherlands and colleagues conducted a randomized clinical trial to quantify the effect of a single intraoperative dose of the corticosteroid dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery.
“Prophylactic corticosteroids are often administered during cardiac surgery to attenuate [lessen] the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking,” according to background information in the article.
The study included 4,494 patients ages 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in the Netherlands, enrolled between April 2006 and November 2011. Patients were randomly assigned to receive a single intraoperative dose of dexamethasone (n = 2,239) or placebo (n = 2,255). The primary outcome measure for the study was a composite of death, heart attack, stroke, renal failure, or respiratory failure, within 30 days of randomization.
A total of 157 patients in the dexamethasone group (7.0 percent) and 191 patients in the placebo group (8.5 percent) reached the primary study end point (absolute risk reduction, -1.5 percent). “Our randomized study of 4,494 patients undergoing cardiac surgery failed to show a statistically significant benefit of intraoperative administration of dexamethasone on the incidence of the composite primary study end point of major adverse events,” the authors write.
(JAMA.2012;308:1761-1767. Available pre-embargo to the media at http://media.jamanetwork.com)
Media Advisory: To contact Jan M. Dieleman, M.D., email email@example.com.
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Most High-Risk Cardiovascular Devices Approved Without Comparative Effectiveness Data
Connie E. Chen, M.D., of the Stanford Hospital and Clinics, Palo Alto, Calif., and colleagues conducted a study to examine the type of controls used by the Food and Drug Administration in evaluating comparative effectiveness during premarket approval of cardiovascular devices.
“Use of a comparator group is not required in studies used for approval of medical devices, in contrast to drugs, which require 2 randomized controlled trials. … Unlike drugs, device trials frequently use control data from previous trials (historical controls) and performance benchmarks imputed from prior studies (objective performance criteria; OPC) in evaluating outcomes. However, the lack of active controls raises concerns about selection bias and validity,” the authors write.
As reported in a Research Letter, data were extracted from publicly available FDA summaries of safety and effectiveness data. Summaries representing all high-risk cardiovascular devices approved by the FDA between January 1, 2000, and December 31, 2011, were analyzed. All primary end points were examined to determine the type of controls with which the device was compared. Comparative effectiveness research was defined as use of active controls in evaluating primary end points.
“The 121 summaries identified contained 203 supporting clinical studies. These studies used 353 primary end points, of which 40 percent (n = 140) were evaluated against an active control, 13 percent (n = 45) against a historical control, 26 percent (n = 90) against an OPC, and 22 percent (n = 78) against no control. Thirty-six percent (74/203) of studies included at least 1 primary end point evaluated against an active control; 48 percent (58/121) of devices had an active control in at least 1 supporting study, while 35 percent (42/121) of devices were approved without data from any control or OPC,” the authors write.
“It is hard to know if a new device is safe and more effective than alternative treatments unless it is compared with conventional treatment. While occasionally use of active controls may not be possible, such as ventricular assist devices, more frequent use of a comparator group may help to better inform clinical and regulatory decisions.”
(JAMA.2012;308:1740-1742. Available pre-embargo to the media at http://media.jamanetwork.com)
Viewpoints in This Week’s JAMA
Transforming Clinical Trials in Cardiovascular Disease – Mission Critical for Health and Economic Well-being
Elliott M. Antman, M.D., of Brigham and Women’s Hospital, Boston, and Robert A. Harrington, M.D., of the Stanford University Department of Medicine, Stanford, Calif., discuss changes in design and quality of randomized controlled trials (RCTs) involving cardiovascular disease.
“These innovations to RCTs need to occur in concert with ongoing efforts by the Food and Drug Administration (FDA) to promote innovations in regulatory science. Academic and industry stakeholders need to collaborate with the FDA to establish common definitions of end points and case report form data elements and the appropriate use of biomarkers and genetic testing in RCTs. Researchers also need to learn how to deal with the regulatory challenges of establishing new approval methods when generic drugs used in managing cardiovascular disease are found to be effective for ‘off-label’ indications. Similarly, researchers and clinicians need to consider innovative approaches when observational data raise the hypothesis that approved drugs used broadly in the population may need to be re-evaluated in new RCTs to define appropriate use.”
(JAMA.2012;308:1743-1744. Available pre-embargo to the media at http://media.jamanetwork.com)
Preventing and Controlling Hypertension in the Era of Genomic Innovation and Environmental Transformation
Donna K. Arnett, M.S.P.H., Ph.D., and Steven A. Claas, M.S., of the University of Alabama at Birmingham, examine how genomics has contributed to the understanding of hypertension, and the relationship of environmental factors with the occurrence of hypertension.
“The current understanding of hypertension genomics and the ability to create environments that are not at odds with the evolutionary legacy have never been greater, and gains on both of these fronts are likely. More importantly, the medical community has only just begun to illuminate how these 2 domains interact to create sustainable health. Today, there is an unprecedented opportunity to synergistically merge genomic knowledge and environmental acumen to prevent and control hypertension.”
(JAMA.2012;308:1745-1746. Available pre-embargo to the media at http://media.jamanetwork.com)
The Future of Cardiovascular Clinical Research – Informatics, Clinical Investigators, and Community Engagement
Robert M. Califf, M.D., of Duke University Medical Center, Durham, N.C., and colleagues write that reductions in cardiovascular illness and death will depend on enhanced individual and community engagement with the research enterprise, and that informatics will play an important role.
“If all Americans have an electronic health record that supports individual care, and data are collected using common standards and housed in data warehouses jointly owned by health care delivery systems and local communities, this resource could be used to design and conduct health interventions; investigate the intersection of biology, culture, and environment; and provide a continuous learning environment. With a learning health care delivery system in place, when effect sizes for an intervention are less than an odds ratio or relative risk of 1.6 (in the range of most effective therapies), randomization could occur as an intrinsic element of an intervention at the individual or neighborhood scale, increasing the ability to generate high-level evidence by an order of magnitude at a much lower cost. That dream, described as an aspiration in the 2002 NIH Roadmap, is now within reach.”
(JAMA.2012;308:1747-1748. Available pre-embargo to the media at http://media.jamanetwork.com)
Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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