Browsing by Author "Califf, Robert M"

Now showing 1 - 9 of 9
  • Thumbnail Image
    ItemOpen Access
    Acquisition, Analysis, and Sharing of Data in 2015 and Beyond: A Survey of the Landscape: A Conference Report From the American Heart Association Data Summit 2015.
    (J Am Heart Assoc, 2015-11-05) Antman, Elliott M; Benjamin, Emelia J; Harrington, Robert A; Houser, Steven R; Peterson, Eric D; Bauman, Mary Ann; Brown, Nancy; Bufalino, Vincent; Califf, Robert M; Creager, Mark A; Daugherty, Alan; Demets, David L; Dennis, Bernard P; Ebadollahi, Shahram; Jessup, Mariell; Lauer, Michael S; Lo, Bernard; MacRae, Calum A; McConnell, Michael V; McCray, Alexa T; Mello, Michelle M; Mueller, Eric; Newburger, Jane W; Okun, Sally; Packer, Milton; Philippakis, Anthony; Ping, Peipei; Prasoon, Prad; Roger, Véronique L; Singer, Steve; Temple, Robert; Turner, Melanie B; Vigilante, Kevin; Warner, John; Wayte, Patrick; American Heart Association Data Sharing Summit Attendees
    BACKGROUND: A 1.5-day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's (AHA's) near-term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. METHODS AND RESULTS: A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference. Presentation topics included updates on data as viewed from conventional medical and nonmedical sources, building and using Big Data repositories, articulation of the goals of data sharing, and principles of responsible data sharing. Facilitated breakout sessions were conducted to examine what each of the 7 stakeholder domains wants from Big Data under ideal circumstances and the possible roles that the AHA might play in meeting their needs. Important areas that are high priorities for further study regarding Big Data include a description of the methodology of how to acquire and analyze findings, validation of the veracity of discoveries from such research, and integration into investigative and clinical care aspects of future cardiovascular and stroke medicine. Potential roles that the AHA might consider include facilitating a standards discussion (eg, tools, methodology, and appropriate data use), providing education (eg, healthcare providers, patients, investigators), and helping build an interoperable digital ecosystem in cardiovascular and stroke science. CONCLUSION: There was a consensus across stakeholder domains that Big Data holds great promise for revolutionizing the way cardiovascular and stroke research is conducted and clinical care is delivered; however, there is a clear need for the creation of a vision of how to use it to achieve the desired goals. Potential roles for the AHA center around facilitating a discussion of standards, providing education, and helping establish a cardiovascular digital ecosystem. This ecosystem should be interoperable and needs to interface with the rapidly growing digital object environment of the modern-day healthcare system.
  • Thumbnail Image
    ItemOpen Access
    Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012.
    (American heart journal, 2014-09) Hess, Paul L; Mirro, Michael J; Diener, Hans-Christoph; Eikelboom, John W; Al-Khatib, Sana M; Hylek, Elaine M; Bosworth, Hayden B; Gersh, Bernard J; Singer, Daniel E; Flaker, Greg; Mega, Jessica L; Peterson, Eric D; Rumsfeld, John S; Steinberg, Benjamin A; Kakkar, Ajay K; Califf, Robert M; Granger, Christopher B; Atrial Fibrillation Think-Tank Participants
    Approximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives.
  • Thumbnail Image
    ItemOpen Access
    Compliance with results reporting at ClinicalTrials.gov.
    (N Engl J Med, 2015-03-12) Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert M
    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. (Funded by the Clinical Trials Transformation Initiative and the NIH.).
  • Thumbnail Image
    ItemOpen Access
    Consistency of financial interest disclosures in the biomedical literature: the case of coronary stents.
    (PLoS One, 2008-05-07) Weinfurt, Kevin P; Seils, Damon M; Tzeng, Janice P; Lin, Li; Schulman, Kevin A; Califf, Robert M
    BACKGROUND: Disclosure of authors' financial interests has been proposed as a strategy for protecting the integrity of the biomedical literature. We examined whether authors' financial interests were disclosed consistently in articles on coronary stents published in 2006. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed for English-language articles published in 2006 that provided evidence or guidance regarding the use of coronary artery stents. We recorded article characteristics, including information about authors' financial disclosures. The main outcome measures were the prevalence, nature, and consistency of financial disclosures. There were 746 articles, 2985 authors, and 135 journals in the database. Eighty-three percent of the articles did not contain disclosure statements for any author (including declarations of no interests). Only 6% of authors had an article with a disclosure statement. In comparisons between articles by the same author, the types of disagreement were as follows: no disclosure statements vs declarations of no interests (64%); specific disclosures vs no disclosure statements (34%); and specific disclosures vs declarations of no interests (2%). Among the 75 authors who disclosed at least 1 relationship with an organization, there were 2 cases (3%) in which the organization was disclosed in every article the author wrote. CONCLUSIONS/SIGNIFICANCE: In the rare instances when financial interests were disclosed, they were not disclosed consistently, suggesting that there are problems with transparency in an area of the literature that has important implications for patient care. Our findings suggest that the inconsistencies we observed are due to both the policies of journals and the behavior of some authors.
  • Thumbnail Image
    ItemOpen Access
    Generating evidence for therapeutic effects: the need for well-conducted randomized trials.
    (The Journal of clinical investigation, 2020-12-03) Califf, Robert M; Curtis, Lesley H; Harrington, Robert A; Hernandez, Adrian F; Peterson, Eric D
    In this viewpoint, Robert Califf, former commissioner of the U.S. Food and Drug Administration, and colleagues reflect on how to approach questions about which patient treatments and strategies work, particularly in light of the tremendous pressure on the government and biomedical research enterprise to quickly develop safe, effective therapies during the SARS-CoV-2 pandemic.
  • Thumbnail Image
    ItemOpen Access
    Heart Failure With Preserved Ejection Fraction Expert Panel Report: Current Controversies and Implications for Clinical Trials
    (JACC: Heart Failure, 2018-08-01) Parikh, Kishan S; Sharma, Kavita; Fiuzat, Mona; Surks, Howard K; George, Jyothis T; Honarpour, Narimon; Depre, Christopher; Desvigne-Nickens, Patrice; Nkulikiyinka, Richard; Lewis, Gregory D; Gomberg-Maitland, Mardi; O'Connor, Christopher M; Stockbridge, Norman; Califf, Robert M; Konstam, Marvin A; Januzzi, James L; Solomon, Scott D; Borlaug, Barry A; Shah, Sanjiv J; Redfield, Margaret M; Felker, G Michael
    © 2018 American College of Cardiology Foundation The number of persons with heart failure has continued to rise over the last several years. Approximately one-half of those living with heart failure have heart failure with preserved ejection fraction, but critical unsolved questions remain across the spectrum of basic, translational, clinical, and population research in heart failure with preserved ejection fraction. In this study, the authors summarize existing knowledge, persistent controversies, and gaps in evidence with regard to the understanding of heart failure with preserved ejection fraction. Our analysis is based on an expert panel discussion “Think Tank” meeting that included representatives from academia, the National Institutes of Health, the U.S. Food and Drug Administration, the Centers for Medicare & Medicaid Services, and industry.
  • Thumbnail Image
    ItemOpen Access
    Portfolio of clinical research in adult cardiovascular disease as reflected in ClinicalTrials.gov.
    (Journal of the American Heart Association, 2013-09-26) Alexander, Karen P; Kong, David F; Starr, Aijing Z; Kramer, Judith; Chiswell, Karen; Tasneem, Asba; Califf, Robert M
    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 1220 free-text 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.
  • Thumbnail Image
    ItemOpen Access
    Randomized Trials Versus Common Sense and Clinical Observation: JACC Review Topic of the Week.
    (Journal of the American College of Cardiology, 2020-08) Fanaroff, Alexander C; Califf, Robert M; Harrington, Robert A; Granger, Christopher B; McMurray, John JV; Patel, Manesh R; Bhatt, Deepak L; Windecker, Stephan; Hernandez, Adrian F; Gibson, C Michael; Alexander, John H; Lopes, Renato D
    Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making. However, over the past 4 decades, results from well-done RCTs have repeatedly contradicted practices supported by common sense and clinical observation. Common sense and clinical observation fail for several reasons: incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems. Concerns about traditional RCT models are legitimate, but randomization remains a critical tool to understand the causal relationship between treatments and outcomes. Instead, development and promulgation of tools to apply randomization to real-world data are needed to build the best evidence base in cardiovascular medicine.
  • Thumbnail Image
    ItemOpen Access
    The left bundle-branch block puzzle in the 2013 ST-elevation myocardial infarction guideline: from falsely declaring emergency to denying reperfusion in a high-risk population. Are the Sgarbossa Criteria ready for prime time?
    (American heart journal, 2013-09) Cai, Qiangjun; Mehta, Nilay; Sgarbossa, Elena B; Pinski, Sergio L; Wagner, Galen S; Califf, Robert M; Barbagelata, Alejandro
    Prompt and accurate identification of ST-elevation myocardial infarction (STEMI) in the presence of left bundle-branch block (LBBB) remains difficult. The 2004 STEMI guideline recommended emergent reperfusion therapy to patients with suspected ischemia and new or presumably new LBBB. These recommendations have led to frequent false catheterization laboratory activation and inappropriate fibrinolytic therapy because most patients with suspected ischemia and new or presumably new LBBB do not have acute coronary artery occlusion on angiography. The new 2013 STEMI guideline makes a drastic change by removing previous recommendations. Therefore, patients with suspected ischemia and new or presumably new LBBB would no longer be treated as STEMI equivalent. The new guideline fails to recognize that some patients with suspected ischemia and LBBB do have STEMI, and denying reperfusion therapy could be fatal. The Sgarbossa electrocardiography criteria are the most validated tool to aid in the diagnosis of STEMI in the presence of LBBB. A Sgarbossa score of ≥3 has a superb specificity (98%) and positive predictive value for acute myocardial infarction and angiography-confirmed acute coronary occlusion. Thus, we propose a diagnosis and triage algorithm incorporating the Sgarbossa criteria to quickly and accurately identify, among patients presenting with chest pain and new or presumably new LBBB, those with acute coronary artery occlusion. This is a high-risk population in which reperfusion therapy would be denied by the 2013 STEMI guideline. Our algorithm will also significantly reduce false catheterization laboratory activation and inappropriate fibrinolytic therapy, the inevitable consequence of the 2004 STEMI guideline.