Robert M. Califf's research while affiliated with Duke University and other places

Publications (928)

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Background Coronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear. Methods In the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed...
Article
Because of significant adaptations forced by the COVID-19 pandemic, resultant changes within health care delivery and clinical research introduced the potential for evaluation of novel evidence generation approaches in oncology. On July 26 and 27, 2021, the National Academies of Science, Engineering, and Medicine, National Cancer Policy Forum hoste...
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Objectives We assessed the relationship between the Patient Health Questionnaire-9 (PHQ-9) at intake and other measurements intended to assess biological factors, markers of disease and health status. Design, setting and participants We performed a cross-sectional analysis of 2365 participants from the Baseline Health Study, a prospective cohort o...
Preprint
Background: The General Anxiety Disorder-7 (GAD-7) questionnaire is a standard tool used for screening and follow-up of patients with Generalized Anxiety Disorder (GAD). Although it is generally accepted that anxiety correlates with clinical and psychosocial stressors, precise quantitative data is limited on the relations among GAD-7, traditional b...
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Patients with HF are surrounded by an ecosystem comprising multiple people and entities that are suboptimally deployed and not equipped to produce the desired result: better outcomes at a lower cost that also yield a better, more equitable experience for patients, their families, and the clinicians who serve them. It is now technically possible to...
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Background In event‐driven clinical trials, study termination is based on accrual of a target number of primary efficacy events. For noninferiority trials in which superiority is conditionally examined, the ideal cohort in which to track event accrual is unclear. We used data from the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibiti...
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Importance The most common screening tool for depression is the Patient Health Questionnaire-9 (PHQ-9). Despite extensive research on the clinical and behavioral implications of the PHQ-9, data are limited on the relationship between PHQ-9 scores and social determinants of health and disease. Objective To assess the relationship between the PHQ-9...
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As society has moved past the initial phase of the COVID-19 crisis that relied on broad-spectrum shutdowns as a stopgap method, industries and institutions have faced the daunting question of how to return to a stabilized state of activities and more fully reopen the economy. A core problem is how to return people to their workplaces and educationa...
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Newer data platforms offer increased opportunity to share multidimensional health data with research participants, but the preferences of participants for which data to receive and how is evolving. Our objective is to describe the preferences and expectations of participants for the return of individual research results within Project Baseline Heal...
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Background The increasing importance placed by medical journals for dissemination of published articles on social media, such as posting Altmetric scores, has further expedited the need for differentiating bona fide science from pseudo-science. The “Kardashian index” (a.k.a., K-index) was suggested, which correlates the citations of a scientist wit...
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Introduction In the 2016 U.S. Presidential election, voters in communities with recent stagnation or decline in life expectancy were more likely to vote for the Republican candidate than in prior Presidential elections. We aimed to assess the association between change in life expectancy and voting patterns in the 2020 Presidential election. Metho...
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The laws and policies for informed consent and other aspects of participant safety in clinical trials receive considerable attention. Equally important are laws designed to ensure that trial participation advances medical science—because this potential benefit is what makes even the smallest set of risks acceptable. The Food and Drug Administration...
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Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real-world evidence (RWE) in the evaluation of new treatments or products. RWE studies often rely on real-world data (RWD), including data extracted from healthcare records or data captured by mobile phones or...
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Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real‐world evidence (RWE) in the evaluation of new treatments or products. Real‐world clinical trials or pragmatic trials often differ from traditional clinical trials in the use of open‐label or nonblinded tr...
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Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real‐world evidence (RWE) in the evaluation of new treatments or products. The RWE label has been used to refer to a variety of departures from the methods of traditional randomized controlled trials. Recogniz...
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The randomized controlled trial (RCT) is the gold standard for evaluating the causal effects of medications. Limitations of RCTs have led to increasing interst in using real‐world evidence (RWE) to augment RCT evidence and inform decision‐making on medications. Although RWE can be either randomized or nonrandomized, nonrandomized RWE can capitalize...
Preprint
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BACKGROUND Although effective mental health treatments exist, the ability to match individuals to optimal treatment options is poor and timely assessment of response is difficult. One reason for these challenges is the lack of objective measurement of psychiatric symptoms and behaviors of daily function. Sensors and active tasks enabled by smartpho...
Preprint
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Background: Much of the early data on COVID-19 symptomatology was captured in the hospital setting. In a community setting the symptoms most predictive of SARS-CoV-2 positivity may be different. Data from the California sites of a COVID-19 community testing program are presented here. Methods: Prior to being tested, participants in the Baseline COV...
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Background Although effective mental health treatments exist, the ability to match individuals to optimal treatments is poor, and timely assessment of response is difficult. One reason for these challenges is the lack of objective measurement of psychiatric symptoms. Sensors and active tasks recorded by smartphones provide a low-burden, low-cost, a...
Preprint
Full-text available
As society has moved past the initial phase of the COVID-19 crisis that relied on broad-spectrum shutdowns as a stopgap method, industries and institutions have faced the daunting question of how to return to a stabilized state of activities and more fully reopen the economy. A core problem is how to return people to their workplaces and educationa...
Preprint
Full-text available
Introduction In the 2016 U.S. Presidential election, voters in communities with recent stagnation or decline in life expectancy were more likely to vote for the Republican candidate than in prior Presidential elections. We aimed to assess the association between change in life expectancy and voting patterns in 2018 U.S. House of Representative elec...
Article
Background: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial. Methods and results: T...
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Importance: Adherence to the Consolidated Standards of Reporting Trials (CONSORT) for randomized clinical trials is associated with improvingquality because inadequate reporting in randomized clinical trials may complicate the interpretation and the application of findings to clinical care. Objective: To evaluate an automated reporting checklist...
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Background An increased risk of malignancy was reported with simvastatin/ezetimibe in 1,873 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial. Objectives The purpose of this study was to clarify this unexpected finding in a larger sample size of patients stabilized after acute coronary syndrome, we conducted a prospective s...
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Amid the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, substantial effort is being directed toward mining databases and publishing case series and reports that may provide insights into the epidemiology and clinical management of coronavirus disease 2019 (COVID-19). However, there is growing concern about whether attempts t...
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The pipeline of new cardiovascular drugs is relatively limited compared with many other clinical areas. Challenges causing lagging drug innovation include the duration and expense of cardiovascular clinical trials needed for regulatory evaluation and approvals, which generally must demonstrate noninferiority to existing standards of care and measur...
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Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a “digital clinical trial...
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Emerging data science techniques of predictive analytics expand the quality and quantity of complex data relevant to human health and provide opportunities for understanding and control of conditions such as heart, lung, blood, and sleep disorders. To realize these opportunities, the information sources, the data science tools that use the informat...
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The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, envir...
Article
Wide variation in cardiovascular disease age-adjusted mortality rates (AAMRs) has been noted among counties in the US.¹ Rural residents experience higher death rates compared with residents of urban areas, particularly from potentially preventable causes.² We examined temporal trends in cardiovascular disease AAMRs overall and across subgroups stra...
Article
Background Clinical guideline documents reflect the evidence supporting clinical practice, but few recommendations in cardiovascular guidelines are supported by evidence from randomized controlled trials (RCTs), the highest level of evidence. Incentives for generating evidence from RCTs differ by topic of guideline recommendation, and it is uncerta...
Article
The term phenotype is so commonly used that we often assume that we each mean the same thing. The general definition, the set of observable characteristics of an individual resulting from the interaction of their genotype with the environment, is often left to the eye of the beholder. Whether applied to the multiple levels of biological phenomena o...
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Understanding and addressing the unique health needs of people residing in rural America is critical to the American Heart Association’s pursuit of a world with longer, healthier lives. Improving the health of rural populations is consistent with the American Heart Association’s commitment to health equity and its focus on social determinants of he...
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The availability of large datasets from multiple sources [e.g. registries, biobanks, electronic health records (EHRs), claims or billing databases, implantable devices, wearable sensors, and mobile apps], coupled with advances in computing and analytic technologies, have provided new opportunities for conducting innovative health research. Equally,...
Article
Responding to concerns about the potential for increased risk of adverse cardiovascular (CV) outcomes, specifically myocardial infarction, associated with certain glucose-lowering therapies, the U.S. Food and Drug Administration and the Committee for Medicinal Products for Human Use of the European Medicines Agency issued guidance to the pharmaceut...
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Big data (BD) in pediatric medication safety research provides many opportunities to improve the safety and health of children. The number of pediatric medication and device trials has increased in part because of the past 20 years of US legislation requiring and incentivizing study of the effects of medical products in children (Food and Drug Admi...
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The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical tri...
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In Reply We agree with Dr Cohen and colleagues that any solution to the escalation of drug pricing must support continuing innovation and drug development. Unfortunately, their critique presents a set of false choices that offers no remedy to the problem that a growing number of patients are experiencing serious health consequences from inability t...
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Project management expertise is employed across many professional sectors, including clinical research organizations, to ensure that efforts undertaken by the organization are completed on time and according to specifications and are capable of achieving the needed impact. Increasingly, project leaders (PLs) who possess this expertise are being emp...
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Background Addition of ezetimibe to statin therapy reduces the risk of recurrent cardiovascular (CV) events in patients with prior acute coronary syndrome (ACS). The role of biomarkers in identifying subsets of patients who may derive greater clinical benefit with ezetimibe is unknown. Objectives This study sought to evaluate the role of establish...
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Although the sharing of misleading information is likely as old as humanity, an unfortunate concomitant of the current digital environment is the amplification and accelerated spread of medical misinformation.¹,2 Growing distrust of medical professionals is causing some people to eschew drugs that have been proven effective, such as statins for hyp...
Article
Skin cancer is the most common malignancy in the United States and is estimated to affect more than 3.3 million individuals each year.¹ Photoprotection, including sunscreen use for areas of skin not covered by sun protective clothing or shade, aims to reduce exposure to UV radiation, likely the main risk factor for the development of skin cancer.
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US drug costs have reached unacceptable and unsustainable levels. Evidence shows that “financial toxicity” arising from drug costs and other medical expenses is reducing financial security for many families¹ and prompting difficult choices, as patients defer or forgo therapies they cannot afford.² In stark contrast, comparable countries negotiate d...
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Importance Clinical decisions are ideally based on evidence generated from multiple randomized controlled trials (RCTs) evaluating clinical outcomes, but historically, few clinical guideline recommendations have been based entirely on this type of evidence. Objective To determine the class and level of evidence (LOE) supporting current major cardi...
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Although advances in care have spurred improvements in cardiovascular outcomes, cardiovascular disease remains the leading cause of death in the United States and around the world. Previous declines in cardiovascular disease mortality have slowed and even reversed for certain demographics. Further concerns exist with regard to cardiovascular drug i...
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Background: Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials. Methods and results: We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outc...
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Seven former commissioners of the Food and Drug Administration (FDA) from both sides of the political aisle recommend that the FDA be moved out of the Department of Health and Human Services and reconfigured as an independent federal agency. We believe that such a reengineering would promote reliance on consistent science-based regulation and ensur...
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Previous decades have seen significant progress in the biological understanding of cardiovascular disease, as well as major advances in computational and information technologies. However, anticipated improvements in outcomes, quality, and cost of cardiovascular medicine at the individual and population levels from these advances have lagged expect...
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In Reply It is promising that institutes such as the NHGRI have chosen to invest in projects addressing the return of individual research results, as Dr Kaufman and colleagues highlight. Conducting rigorous research to answer the “what, when, and how” to return these results is important to move the field forward.¹ Although some extant literature e...
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Psychiatry has been limited by historically rooted practices centered primarily on subjective observation. Fields such as oncology have progressed toward data-driven clinical decision-making that combines subjective clinical assessment of symptoms and preferences with biological measures such as genetics, biomarkers, imaging, and integrative physio...
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Abstract Health professionals within the medical community feel that the principles of humanism in medicine have not been a point of emphasis for information and computer technology in healthcare. There is concern that the electronic health record is eroding the patient-clinician relationship and distancing clinicians from their patients. New analy...
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Background: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indica...
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Background: Globalization of clinical trials fosters inclusion of higher and lower income countries, but the influence of enrolling country income level on heart failure trial performance is unclear. This study sought to evaluate associations between enrolling country income level, acute heart failure patient profile, protocol completion, and tria...
Article
Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarcti...
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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 preserv...
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Research data may be of great utility to study participants and their clinicians in understanding and managing the health of patients who participate in research, depending on the clinical context and nature of results. In addition, increasing amounts of digital data are generated by commercial health products, such as accelerometers and smart watc...
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Real-world data (RWD) has been defined as data generated outside of traditional randomized clinical trials (RCTs). Though RWD has received increasing attention from regulatory authorities and professional societies, dividing evidence into that derived from 'real-world' vs. 'non-real-world' sources provides only one element of a much larger framewor...
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How is it possible that, despite staggering growth in spending on health care, the United States ranks in the middle of economically developed countries in health status¹ and has now experienced its second consecutive year² of decreases in life expectancy? Just as vexing, the declines in both relative and absolute status compared with international...
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Biomarkers are critical to the rational development of medical therapeutics, but significant confusion persists regarding fundamental definitions and concepts involved in their use in research and clinical practice, particularly in the fields of chronic disease and nutrition. Clarification of the definitions of different biomarkers and a better und...
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The current heart failure clinical trial environment is strained by increasing complexity and cost, regulatory requirements, competing demands on stakeholders, implementation challenges, and decreasing patient and investigator participation. To begin the process of developing potentially effective strategies and tactics, stakeholders including pati...
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In this issue of JAMA Internal Medicine, Fralick and colleagues¹ create a straw man to demonstrate that observational treatment comparisons could be useful for expanding indications for medical products. The authors modeled the Ongoing Telmisartan Alone and in Combination with Ramipril Global End-point Trial (ONTARGET),² which compared the angioten...
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When people use medical products, they generally expect that the benefits of doing so will outweigh the risks in terms of living longer, feeling better, or improving their functional status. However, most drugs and biologics and many medical devices that enter early evaluation in humans are found either to have no benefit or to have risks that outw...
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Few physicians consider cosmetics and related products relevant to their professional lives. Cosmetics, of course, are used to alter the body’s appearance, not its actual structure or function. However, the distinction between substances that only alter bodily appearance or aesthetics and medicinal compounds that affect the body’s structure or heal...
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Percutaneous treatment of valvular heart disease is a modern miracle. A decade ago, it was inconceivable to all but a few visionary inventors that a catheter–based approach could be used to replace a cardiac valve, thus eliminating the need for a thoracotomy with all of its associated costs, inconvenience, and potential for major adverse outcomes....