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We analyzed changes in total costs for National Institutes of Health (NIH) awarded Research Project Grants (RPGs) issued from fiscal years (FYs) 1998 to 2021 . Costs are measured in ‘nominal’ terms, meaning exactly as stated, or in ‘real’ terms, meaning after adjustment for inflation. The NIH uses a data-driven price index – the Biomedical Research and Development Price Index (BRDPI) – to account for inflation, enabling assessment of changes in real (that is, BRDPI-adjusted) costs over time. The BRDPI was higher than the general inflation rate from FY1998 until FY2012; since then the BRDPI has been similar to the general inflation rate likely due to caps on senior faculty salary support. Despite increases in nominal costs, recent years have seen increases in the absolute numbers of RPG and R01 awards. Real average and median RPG costs increased during the NIH-doubling (FY1998 to FY2003), decreased after the doubling and have remained relatively stable since. Of note, though, the degree of variation of RPG costs has changed over time, with more marked extremes observed on both higher and lower levels of cost. On both ends of the cost spectrum, the agency is funding a greater proportion of solicited projects, with nearly half of RPG money going toward solicited projects. After adjusting for confounders, we find no independent association of time with BRDPI-adjusted costs; in other words, changes in real costs are largely explained by changes in the composition of the NIH-grant portfolio.

A previous report found an association of topic choice with race-based funding disparities among R01 applications submitted to the National Institutes of Health (‘NIH’) between 2011 and 2015. Applications submitted by African American or Black (‘AAB’) Principal Investigators (‘PIs’) skewed toward a small number of topics that were less likely to be funded (or ‘awarded’). It was suggested that lower award rates may be related to topic-related biases of peer reviewers. However, the report did not account for differential funding ecologies among NIH Institutes and Centers (‘ICs’). In a re-analysis, we find that 10% of 148 topics account for 50% of applications submitted by AAB PIs. These applications on ‘AAB Preferred’ topics were funded at lower rates, but peer review outcomes were similar. The lower rate of funding for these topics was primarily due to their assignment to ICs with lower award rates, not to peer-reviewer preferences.

The COVID-19 pandemic has been mitigated primarily using social and behavioral intervention strategies, and these strategies have social and economic impacts, as well as potential downstream health impacts that require further study. Digital and community-based interventions are being increasingly relied upon to address these health impacts and bridge the gap in health care access despite insufficient research of these interventions as a replacement for, not an adjunct to, in-person clinical care. As SARS-CoV-2 testing expands, research on encouraging uptake and appropriate interpretation of these test results is needed. All of these issues are disproportionately impacting underserved, vulnerable, and health disparities populations. This commentary describes the various initiatives of the National Institutes of Health to address these social, behavioral, economic, and health disparities impacts of the pandemic, the findings from which can improve our response to the current pandemic and prepare us better for future infectious disease outbreaks.

Sexual harassment, including gender harassment, presents an unacceptable barrier that prevents women from achieving their rightful place in science, and robs society and the scientific enterprise of diverse and critical talent. As the largest single funder of biomedical research in the world, the U.S. National Institutes of Health (NIH) bears a responsibility to take action to put an end to this behavior. In 2019, the NIH began to bolster its policies and practices to address and prevent sexual harassment. This included new communication channels to inform the agency of instances of sexual harassment related to NIH-funded research. This week, the NIH announces a change that will hold grantee institutions and investigators accountable for this misconduct, to further foster a culture whereby sexual harassment and other inappropriate behaviors are not tolerated in the research and training environment. Last year, an Advisory Committee to the Director (ACD) of the NIH presented a report and recommendations to end sexual harassment. A major theme of this report was the need for increased transparency and accountability in the reporting of professional misconduct, especially sexual harassment. The cases of sexual harassment that surfaced in the wake of the U.S. National Academies of Sciences, Engineering, and Medicine (NASEM) 2018 report highlighted a substantial gap in the NIH's oversight of the research enterprise: There was no straightforward mechanism for the agency to learn of sexual harassment or other misconduct taking place at grantee institutions in the context of NIH-funded research. It was not uncommon for the NIH to discover such cases through the media, amid rightful public outcry. Holding institutions and investigators accountable for this behavior was challenging. Over the past year, the NIH has established communication channels for anyone—institutions, targets of harassment, bystanders—to inform the agency about instances when sexual harassment compromised the conduct of an NIH-funded project at a grantee institution. Although voluntary provision of information is important and has improved awareness of, and increased NIH actions on, sexual harassment cases, it does not fully cover issues related to the required reporting of a change in principal investigator (PI) or the transfer of a grant by an NIH grantee institution. Two important areas required more attention: differentiating between instances where an institution removed a PI from a grant because of findings or concerns of sexual harassment from other reasons (such as medical leave or job change); and preventing “passing the harasser,” in which a scientist who changed institutions could evade the consequences of findings of sexual harassment. To close these gaps, the NIH has issued new guidance to grantees that sets clear expectations for reporting to the NIH when a grantee institution has a finding of sexual harassment of a PI named on an NIH grant. The notice also makes it clear that the NIH expects its grant recipients who request changes in either investigators or movement of a grant to a new recipient institution to promptly inform the agency, whether changes are related to concerns about safety and/or work environments (e.g., because of concerns about harassment, bullying, retaliation, or hostile working conditions) (see ). This includes situations where a PI, or other senior personnel, are removed from a grant during the investigation of a serious allegation. The NIH will use such information in making decisions related to grant funding, including putting into place appropriate institutional oversight mechanisms or remedies, or deciding whether to grant institutional requests about personnel on grant awards, thus connecting information to direct consequences. This guidance should also unmask NIH-funded harassers who seek to change institutions without revealing their track record, whether the investigator seeks to take an existing grant to a new institution or leaves an existing grant behind for a new PI to take it over. These questions would have to be answered and would reveal any past misconduct to the new institution. The NASEM report noted that risk factors for climates and cultures that fomented sexual harassment included both the perception that reports of sexual harassment would be ignored and the perception that there would be no consequence for investigators. It is our hope that this new guidance sends a clear message to dispel those perceptions.

Objective The Patient-Centered Outcomes Research Institute (PCORI) uses a unique approach to Merit Review that includes patients and stakeholders as reviewers with scientists, and includes unique review criteria (patient-centeredness and active engagement of end users in the research). This study assessed the extent to which different reviewer types influence review scores and funding outcomes, the emphasis placed on technical merit compared to other criteria by a multistakeholder panel, and the impact of the in-person discussion on agreement among different reviewer types. Methods Cross-sectional analysis of administrative data from PCORI online and in-person Merit Review (N = 1312 applications from the five funding cycles from November 2013 to August 2015). Linear and logistic regression models were used to analyze the data. Results For all reviewer types, final review scores were associated with at least one review criterion score from each of the three reviewer types. The strongest predictor of final overall scores for all reviewer types was scientists’ prediscussion ratings of technical merit. All reviewers’ prediscussion ratings of the potential to improve health care and outcomes, and scientists’ ratings of technical merit and patient-centeredness, were associated with funding success. For each reviewer type, overall impact scores from the online scoring were changed on at least half of the applications at the in-person panel discussion. Score agreement across reviewer types was greater after panel discussion. Conclusions Scientist, patient, and stakeholder views all contribute to PCORI Merit Review of applications for research funding. Technical merit is critical to funding success but patient and stakeholder ratings of other criteria also influence application disposition.

Historically, women have been underrepresented in clinical research, requiring physicians to extrapolate medical recommendations for women from clinical research done in cohorts consisting predominantly of male participants. While government-funded clinical research has achieved gender parity in phase-3 clinical trials across many biomedical disciplines, improvements are still needed in several facets of women's health research, such as the inclusion of women in early-phase clinical trials, the inclusion of pregnant women and women with physical and intellectual disabilities, the consideration of sex as a biological variable in preclinical research, and the analysis and reporting of sex and gender differences across the full biomedical research continuum. The National Institutes of Health (NIH) Office of Research on Women's Health and the Office of Women's Health of the U.S. Food and Drug Administration (FDA) cosponsored a preconference symposium at the 25th Annual Women's Health Congress, held in Arlington, VA in April, 2017, to highlight gains made and remaining needs regarding the representation of women in clinical research, to introduce innovative procedures and technologies, and to outline revised policy for future studies. Six speakers presented information on a range of subjects related to the representation of women in clinical research and federal initiatives to advance precision medicine. Topics included the following: the return on investment from the NIH-funded Women's Health Initiative; progress in including women in clinical trials for FDA-approved drugs and products; the importance of clinical trials in pregnant women; FDA initiatives to report drug safety during pregnancy; the NIH-funded All of Us Research Program; and efforts to enhance FDA transparency and communications, including the introduction of Drug Trials Snapshots. This article summarizes the major points of the presentations and the discussions that followed.

Randomized clinical trials and large-scale, cohort studies continue to have a critical role in generating evidence in cardiovascular medicine; however, the increasing concern is that ballooning costs threaten the clinical trial enterprise. In this Perspectives article, we discuss the changing landscape of clinical research, and clinical trials in particular, focusing on reasons for the increasing costs and inefficiencies. These reasons include excessively complex design, overly restrictive inclusion and exclusion criteria, burdensome regulations, excessive source-data verification, and concerns about the effect of clinical research conduct on workflow. Thought leaders have called on the clinical research community to consider alternative, transformative business models, including those models that focus on simplicity and leveraging of digital resources. We present some examples of innovative approaches by which some investigators have successfully conducted large-scale, clinical trials at relatively low cost. These examples include randomized registry trials, cluster-randomized trials, adaptive trials, and trials that are fully embedded within digital clinical care or administrative platforms.

Objective To describe and elucidate the time trends of the academic productivity of NHLBI's obesity-related research funding via bibliometric analysis of 30 years of NHLBI-supported obesity-related publications. Methods In total, 3,545 NHLBI-funded obesity-related publications were identified in the Thomson Reuters InCites™ database. Shared references in a community detection algorithm were used to identify publication topics. Characteristics of publications and topical communities were analyzed based on citation count and percentile rank. A percentile rank >90 was considered “highly cited.” Results Obesity-related publications increased more than 10-fold over 30 years, whereas NHLBI-funded publications only increased twofold NHLBI-funded obesity publications were cited a median of 23 times (IQR 8-55, range 0-2,047, mean 52). Thirty percent of these publications were highly cited compared to the expected ten percent. Six topical communities were present in 1983 compared to 16 in 2013. The most highly cited topical areas were sleep (n = 199 publications, 38% highly cited), cardiovascular morbidity and mortality (n = 277, 36%), obesity correlates and consequences (n = 588, 35%), and asthma and inflammation (n = 283, 35%). Conclusions NHLBI-funded obesity publications have contributed substantially to the obesity literature, with many highly cited. Publications grew in number and topical diversity over 30 years and grew at a faster rate than total NHLBI publications.

PURPOSE The current, budget-driven low rate of National Institutes of Health (NIH) funding for biomedical research has raised concerns about new investigators' ability to become independent scientists and their willingness to persist in efforts to secure funding. The authors sought to determine resubmission rates for unfunded National Heart, Lung, and Blood Institute (NHLBI) early stage investigator (ESI) independent research grant (R01) applications and to identify resubmission predictors. METHOD The authors used a retrospective cohort study design and retrieved applications submitted in fiscal years 2010-2012 from NIH electronic research administrative sources. They defined ESI applicants as those who have received no prior R01 (or equivalent) funding and are within 10 years of completion of their terminal research degree or medical residency training. ESI applications at the NHLBI were eligible for special funding consideration if they scored above, but within 10 points of, the payline. The primary outcome was application resubmission after failing to secure funding with the first R01 submission. RESULTS Over half of the unfunded applications were resubmitted. Some of these were discussed and "percentiled." Among percentiled applications, the only significant predictor of resubmission was the percentile score. Over half (59%) of the ESI R01 grants funded by NHLBI in fiscal years 2010-2012 had percentile scores above but within 10 points of the NHLBI payline, and benefited from the special funding considerations. CONCLUSIONS The only independent predictor of resubmission of NHLBI ESI R01 grant applications was percentile score; applicant demographics and institutional factors were not predictive of resubmission.

Growing concerns about the wellbeing and stability of the biomedical research workforce are well documented. Over the last 15 years (since the end of the doubling of the NIH budget), we have observed worsening “hypercompetition” as more scientists vie for fewer available dollars (1, 2). Within this hypercompetitive environment, the research workforce is growing older at a rate that is disproportionate to the general American labor force (3). Late-career investigators have been awarded a greater proportion of available research funding, raising concerns that early-career investigators risk being crowded out of the workforce before they have a chance to launch independent scientific careers (3). Other analysts have suggested that adverse effects are also being felt by midcareer investigators (4); large numbers of meritorious investigators may achieve research independence only to lose it because they are unable to renew their one grant or obtain a second new grant. Fig. 1. The NIH hopes its latest initiative will improve the grant-funding prospects for early- and midcareer investigators. Image courtesy of Shutterstock/Stephen_Payne. In our latest effort to tackle this problem, the NIH is launching the “Next Generation Researchers Initiative,” first announced in June. We believe this initiative will help ameliorate these difficult issues in a direct data-driven manner (5) by taking substantive steps to increase funding opportunities for early- and midcareer investigators. It is not entirely clear why early- and midcareer investigators are disproportionately affected by hypercompetition. Some worry about a review bias that favors more-experienced and better-known researchers (5), making it easier for them to get their applications favorably received at peer review. Others have suggested a resiliency factor (4): experienced, well-networked scientists may hold more than one grant or have access to greater sums of grant and private money, making it easier for them to weather the effects of rejected applications. Regardless of … [↵][1]1To whom correspondence should be addressed. Email: Michael.Lauer{at}nih.gov. [1]: #xref-corresp-1-1

The recently updated US National Institutes of Health clinical trials policies will apply broadly to studies involving experimental manipulations of humans. These studies will require registration and reporting in ClinicalTrials.gov, grant application submission under a clinical trials funding opportunity announcement, and Good Clinical Practice training for investigators.

Topic choice is a previously unappreciated contributor to the lower rate of NIH awards to AA/B scientists., Despite efforts to promote diversity in the biomedical workforce, there remains a lower rate of funding of National Institutes of Health R01 applications submitted by African-American/black (AA/B) scientists relative to white scientists. To identify underlying causes of this funding gap, we analyzed six stages of the application process from 2011 to 2015 and found that disparate outcomes arise at three of the six: decision to discuss, impact score assignment, and a previously unstudied stage, topic choice. Notably, AA/B applicants tend to propose research on topics with lower award rates. These topics include research at the community and population level, as opposed to more fundamental and mechanistic investigations; the latter tend to have higher award rates. Topic choice alone accounts for over 20% of the funding gap after controlling for multiple variables, including the applicant’s prior achievements. Our findings can be used to inform interventions designed to close the funding gap.

An Institute of Medicine report titled U.S. Health in International Perspective: Shorter Lives, Poorer Health documents the decline in the health status of Americans relative to people in other high-income countries, concluding that “Americans are dying and suffering from illness and injury at rates that are demonstrably unnecessary.”1 The report blames many factors, “adverse economic and social conditions” among them. In an editorial in Science discussing the findings of the Institute of Medicine report, Bayer et al2 call for a national commission on health “to address the social causes that have put the USA last among comparable nations.” Although mortality from cardiovascular disease (CVD) in the United States has been on a linear decline since the 1970s, the burden remains high. It accounted for 31.9% of deaths in 2010.3 There is general agreement that the decline is the result, in equal measure, of advances in prevention and advances in treatment. These advances in turn rest on dramatic successes in efforts to understand the biology of CVD that began in the late 1940s.4,5 It has been assumed that the steady downward trend in mortality will continue into the future as further breakthroughs in biological science lead to further advances in prevention and treatment. This view of the future may not be warranted. The prevalence of CVD in the United States is expected to rise 10% between 2010 and 2030.6 This change in the trajectory of cardiovascular burden is the result not only of an aging population but also of a dramatic rise over the past 25 years in obesity and the hypertension, diabetes mellitus, and physical inactivity that accompany weight gain. Although there is no consensus on the precise causes of the obesity epidemic, a dramatic change in the underlying biology of Americans is …

At this year’s State of the Union address, the President announced a new $215 million Precision Medicine Initiative in the 2016 budget that will pioneer a new model of patient-empowered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients [1, 2]. Concurrently, Directors of the National Institutes of Health and the National Cancer Institute, Drs. Francis Collins and Harold Varmus, respectively, published an article in the New England Journal of Medicine that describes two main components of this initiative, a near-term focus on cancer therapy and a longer-term effort to generate knowledge applicable to a wide range of health and disease [3]. This longer-term initiative seeks to generate a cohort of one million or more Americans to “enable better assessment of disease risk, understanding of disease mechanisms, and the prediction of optimal therapy for many more diseases, with the goal of expanding the benefits of precision medicine into myriad aspects of health and healthcare” [3]. Matching treatment to the unique biological, behavioral, or environmental characteristics of the individual is nothing new. Matching blood type for transfusions has been common practice for nearly a century [4]. The guidelines for the management of cholesterol have been based on individual patient factors for over a decade [5]. Tailored behavioral interventions have been evaluated for over two decades. Although early treatment matching studies were disappointing [6], tailored behavioral interventions, especially computerized tailored interventions, have generally been found more efficacious than untailored interventions [7, 8]. The concept of precision medicine is not new, but recent advances in genome sequencing, cohort study designs, health informatics, and mobile/wireless technologies make now an opportune time for a large precision medicine cohort initiative.

Imagine a world where we are able to prevent and pre-empt the burden of cardiovascular, lung, and blood diseases, a world where we are able to capture the promise of personalized precision medicine, where each person receives the right treatment, tailored to his or her needs, at the right time. In

Rationale: The American Recovery and Reinvestment Act (ARRA) allowed National Heart, Lung, and Blood Institute to fund R01 grants that fared less well on peer review than those funded by meeting a payline threshold. It is not clear whether the sudden availability of additional funding enabled research of similar or lesser citation impact than already funded work. Objective: To compare the citation impact of ARRA-funded de novo National Heart, Lung, and Blood Institute R01 grants with concurrent de novo National Heart, Lung, and Blood Institute R01 grants funded by standard payline mechanisms. Methods and Results: We identified de novo (type 1) R01 grants funded by National Heart, Lung, and Blood Institute in fiscal year 2009: these included 458 funded by meeting Institute’s published payline and 165 funded only because of ARRA funding. Compared with payline grants, ARRA grants received fewer total funds (median values, $1.03 versus $1.87 million; P P P =0.61). The similar impact of the ARRA grants persisted even after accounting for potential confounders. Conclusions: Despite shorter durations and lower budgets, ARRA R01 grants had comparable citation outcomes per $million spent to that of contemporaneously funded payline R01 grants.

Objectives The Patient-Centered Outcomes Research Institute (PCORI) includes patients and stakeholders alongside scientists in reviewing research applications using unique review criteria including patient-centeredness and patient and/or stakeholder engagement. To support extension of this unique collaborative model to other funders, information from the reviewers on the review process is needed to understand how scientists and nonscientists evaluate research proposals together. Thus, this study aimed to describe reviewers' perspectives of the interactions during the in-person review panel; to examine the value and challenges of including scientists, patients, and stakeholders together; and to understand the perceived importance of PCORI's review criteria. Methods This study utilized anonymous, cross-sectional surveys (N = 925 respondents from 5 funding cycles: 470 scientists, 217 patients, 238 stakeholders; survey completion rates by cycle: 70–89%) and group interviews (N = 18). Results Reviewers of all types describe PCORI Merit Review as respectful, balanced, and one of reciprocal influence among different reviewer types. Reviewers indicate strong support and value of input from all reviewer types, receptivity to input from others, and the panel chair's incorporation of all views. Patients and stakeholders provide real-world perspectives on importance to patients, research partnership plans, and study feasibility. Challenges included concerns about a lack of technical expertise of patient/stakeholder reviewers and about scientists dominating conversations. The most important criterion for assigning final review scores was technical merit—either alone or in conjunction with patient-centeredness or patient/ stakeholder engagement. Conclusions PCORI Merit Reviewers' self-reports indicate that the perspectives of different reviewer types are influential in panel discussions and Merit Review outcomes.

The current era of worsening hypercompetition in biomedical research has drawn attention to the possibility of decreasing marginal returns from research funding. Recent work has described decreasing marginal returns as a function of annual dollars granted to individual scientists. However, different fields of research incur varying cost structures. Therefore, we developed a Grant Support Index (GSI) that focuses on grant activity code, as opposed to field of study or cost. In a cohort of over 71,000 unique scientists funded by NIH between 1996 and 2014 we analyzed the association of grant support (as measured by annual GSI) with 3 bibliometric outcomes, maximum Relative Citation Ratio (which arguably reflects a scientist’s most influential work), median Relative Citation Ratio, and annual weighted Relative Citation Ratio (which is more dependent on publication counts). We found that for all 3 measures marginal returns decline as annual GSI increases. Thus, we confirm prior findings of decreasing marginal returns with higher levels of research funding support.

Eric S. Williams, MD, MACC, Chair Jonathan L. Halperin, MD, FACC, Co-Chair James A. Arrighi, MD, FACC Eric H. Awtry, MD, FACC Eric R. Bates, MD, FACC Salvatore Costa, MD, FACC Lori Daniels, MD, FACC Akshay Desai, MD, FACC Douglas E. Drachman, MD, FACC Susan Fernandes, LPD, PA-C Rosario

To the editor: The National Heart, Lung, and Blood Institute (NHLBI) community has established a long legacy of research success, resulting in dramatic improvements in longevity and quality of life. To continually advance its mission of research that enhances public health, the NHLBI is embarking

In their critically acclaimed book Decisive , Chip and Dan Heath (from Stanford and Duke Universities) focus on the 4 most pernicious villains of decision-making.1 They are (1) narrow framing, seeing a decision as either X or Y, but not X and Y; (2) confirmation bias, paying attention to only those data that are consistent with prior beliefs; (3) reliance on short-term emotion; and (4) sticking with decisions rather than revising or reversing them if events do not turn out as predicted. The Heath brothers propose that decision-makers adopt a “WRAP” model in which they Widen their options, Reality test their assumptions, Attain distance before deciding, and Prepare to be wrong. The scientific community and the public are understandably interested in how government research sponsors make decisions. This interest has become increasingly acute as funds contract at the same time as research capacity continues to grow.2 The National Institutes of Health (NIH), as the world’s largest public sponsor of biomedical research, is under considerable scrutiny by many stakeholders,2–4 including scientists whose careers often depend on NIH monies, universities that factor NIH funding into their business models, and the public, which looks to the NIH to enable scientific discoveries that will relieve suffering from disease and disability. Many have voiced concern that the NIH should reconsider its business processes, from scientists who wonder about the value of NIH’s funding of big-science epidemiological studies, clinical trials, and research centers3; from policy makers who wonder whether the NIH’s approach to making funding decisions is outmoded2,4; and from critics like Michael Hanna who writes in this issue of Circulation Research that the NIH is failing to properly match funding to population health needs.5 Hanna argues that NIH funding allocations for disease-based research …

To inform the retirement of NIH-owned chimpanzees, we analyzed the outcomes of 764 NIH-owned chimpanzees that were located at various points in time in at least one of 4 specific locations. All chimpanzees considered were alive and at least 10 years of age on January 1, 2005; transfers to a federal sanctuary began a few months later. During a median follow-up of just over 7 years, there were 314 deaths. In a Cox proportional hazards model that accounted for age, sex, and location (which was treated as a time-dependent covariate), age and sex were strong predictors of mortality, but location was only marginally predictive. Among 273 chimpanzees who were transferred to the federal sanctuary, we found no material increased risk in mortality in the first 30 days after arrival. During a median follow-up at the sanctuary of 3.5 years, age was strongly predictive of mortality, but other variables – sex, season of arrival, and ambient temperature on the day of arrival – were not predictive. We confirmed our regression findings using random survival forests. In summary, in a large cohort of captive chimpanzees, we find no evidence of materially important associations of location of residence or recent transfer with premature mortality.

Almost 4 years ago, one of us (F.S.C.) wrote an Editorial ([ 1 ][1]) affirming the continued importance of basic research to the National Institutes of Health (NIH) mission. The Editorial emphasized that basic scientific discovery is the engine that powers the biomedical enterprise, and NIH

Recent clinical trials found that, compared with an angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker and neprilysin inhibitor combination therapy decreased cardiovascular morta...

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.

To describe and elucidate the time trends of the academic productivity of NHLBI's obesity-related research funding via bibliometric analysis of 30 years of NHLBI-supported obesity-related publications.In total, 3,545 NHLBI-funded obesity-related publications were identified in the Thomson Reuters InCites™ database. Shared references in a community detection algorithm were used to identify publication topics. Characteristics of publications and topical communities were analyzed based on citation count and percentile rank. A percentile rank90 was considered "highly cited."Obesity-related publications increased more than 10-fold over 30 years, whereas NHLBI-funded publications only increased twofold NHLBI-funded obesity publications were cited a median of 23 times (IQR 8-55, range 0-2,047, mean 52). Thirty percent of these publications were highly cited compared to the expected ten percent. Six topical communities were present in 1983 compared to 16 in 2013. The most highly cited topical areas were sleep (n = 199 publications, 38% highly cited), cardiovascular morbidity and mortality (n = 277, 36%), obesity correlates and consequences (n = 588, 35%), and asthma and inflammation (n = 283, 35%).NHLBI-funded obesity publications have contributed substantially to the obesity literature, with many highly cited. Publications grew in number and topical diversity over 30 years and grew at a faster rate than total NHLBI publications.

Background We previously demonstrated that cardiovascular (CV) trials funded by the National Heart, Lung, and Blood Institute ( NHLBI ) were more likely to be published in a timely manner and receive high raw citation counts if they focused on clinical endpoints. We did not examine the metrics of trial reports, and our citation measures were limited by failure to account for topic‐related citation behaviors. Methods and Results Of 244 CV trials completed between 2000 and 2011, we identified 184 whose main results were published by August 20, 2014. One investigator who was blinded to rapidity of publication and citation data read each publication and characterized it according to modified Delphi criteria. There were 46 trials (25%) that had Delphi scores of 8 or 9 (of a possible 9); these trials published faster (median time from trial completion to publication, 12.6 [interquartile range { IQR }, 6.7 to 23.3] vs. 21.8 [ IQR , 12.1 to 34.9] months; P IQR , 0.64 to 7.83] vs. 8.41 [ IQR , 1.80 to 24.75]; P =0.002). By random forest regression, we found that the 3 most important predictors of normalized citation percentile values were total costs, intention‐to‐treat analyses (as a modified Delphi quality measure), and focus on clinical (not surrogate) endpoints. Conclusions NHLBI CV trials were more likely to publish results quickly and yield higher topic‐normalized citation impact if they reported results according to well‐defined metrics, along with focus on clinical endpoints.

There are conflicting data about the ability of peer review percentile rankings to predict grant productivity, as measured through publications and citations. To understand the nature of these apparent conflicting findings, we analyzed bibliometric outcomes of 6873 de novo cardiovascular R01 grants funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1980 and 2011. Our outcomes focus on top-10% articles, meaning articles that were cited more often than 90% of other articles on the same topic, of the same type (eg, article, editorial), and published in the same year. The 6873 grants yielded 62 468 articles, of which 13 507 (or 22%) were top-10% articles. There was a modest association between better grant percentile ranking and number of top-10% articles. However, discrimination was poor (area under receiver operating characteristic curve [ROC], 0.52; 95% confidence interval, 0.51–0.53). Furthermore, better percentile ranking was also associated with higher annual and total inflation-adjusted grant budgets. There was no association between grant percentile ranking and grant outcome as assessed by number of top-10% articles per $million spent. Hence, the seemingly conflicting findings on peer review percentile ranking of grants and subsequent productivity largely reflect differing questions and outcomes. Taken together, these findings raise questions about how best National Institutes of Health (NIH) should use peer review assessments to make complex funding decisions.

1.1 Document Development Process #### 1.1.1 Writing Committee Organization The writing committee was selected to represent the American College of Cardiology (ACC) and included a cardiovascular training program director, several active cardiovascular scientists and research methodology

In the current issue of Circulation Research , McCrory et al1 report on the association of heart rate recovery after simple orthostatic challenge—otherwise known as standing up—with all-cause mortality. The authors measured heart rate changes in the first 110 seconds after standing up in 4475 participants of an Irish population–based, cohort study. Immediately after standing, heart rate, as expected, increased but in most subjects started to fall toward resting levels within 10 seconds. The rate of decline between 10 and 20 seconds post orthostatic challenge—or heart rate recovery (HRR10–20)—was lower in older subjects and in subjects with a history of vascular disease. It was also an independent predictor of 4-year mortality: the lower the HRR10–20, the greater the mortality. Article, see p 666 To put these findings in perspective, we go back 28 years, when Schwartz et al2 published a report on a series of experiments that linked baroreceptor function with cardiac response to acute stress. The investigators produced an anterior myocardial infarction (MI) in 301 dogs and …

The past 50 years have witnessed sea changes in cardiovascular medicine and research.1 We came to recognize untreated hypertension as a highly malignant disorder and to recognize that medical treatment of hypertension leads to marked reductions in risk of stroke, myocardial infarction, and premature death. We also came to recognize the power of the randomized trial for assessing candidate strategies for prevention and treatment. Indeed, mega-trials conducted by cardiovascular clinician scientists have played a critical role in defining nearly every major evidence-based intervention, from hypertension treatment to cholesterol reduction and use of aspirin.1

Following the first convincing trials in humans on the benefits of cholesterol lowering for preventionof atheroscleroticrelated events, in 1985, then-Director of the National Heart, Lung, and Blood Institute Robert Levyasserted that the cholesterol“question”wasno longer whether to treat high cholesterol levels, but rather when, inwhom,andhow.1For 30years, it hasbeenwell known that lowering blood cholesterol concentrations by a variety of drugs and other approaches reduces cardiovascular disease (CVD) risk.2Withmore trials in patient groupswith lower risk, including thosewith relatively low levels of low-density lipoprotein cholesterol (LDL-C),3 it has become clear that atherosclerotic cardiovascular disease (ASCVD) canbeprevented by loweringLDL-C levels, especiallywith statindrugs,2,3 in broad segments of the general population. However, the critical questions—when, in whom, and how to lower cholesterol— still remain. This Editorial, with new evidence from 2 reports in this issueof JAMA, addresses 2 of thesequestions: inwhom and how to treat cholesterol levels in 2015. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines2 recommended consideration of statin treatment for 4 clinical scenarios: (1) patients with clinical ASCVD including those with myocardial infarction, angina, or previous coronary revascularization; (2) patients without clinical ASCVD but with an LDL-C level higher than 190 mg/dL and without secondary cause; (3) patients aged 40 through 75 years without clinical ASCVD but with diabetes mellitus and LDL-C levels from 70 through 189mg/dL; and (4) patients aged 40 through 75 years without clinical ASCVD and diabetes, but with an LDL-C level of 70 through 189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher. For the first 3 clinical scenarios there was almost universal acceptance with general agreement that the new recommendations were based on strong and consistent data.4 However, nearly immediately after release of the guidelines therewas considerable scrutiny and controversy regarding the fourth clinical scenario: primary prevention in adults without diabetes butwith an estimated 10-yearASCVD risk of 7.5% or higher. One group reported a set of analyses suggesting that the new ACC/AHA Pooled Cohort Equation overestimated risk in various populations,5 whereas others reported that, in properly selected cohorts, the new equation performedmore accurately thanpreviouslyused risk equations.6 Uncertainties about the accuracy of the risk calculator raised concerns about the wisdom of the newly lowered treatment threshold.Would the new guidelines lead tomassive and unjustified overtreatment ofmillions of people? Thequestionof in whom to use statins lingered. Basedonevidence frommultipleclinical trials, statindrugs havebeenshownto lowerCVDrisk forprimarypreventioneven among relatively low-risk people and even among thosewith relatively low LDL-C concentrations.3 Although a 10-year ASCVD risk threshold of 7.5%orhighermight initially seem to be a low threshold, many, indeed most, CVD events occur among the low-riskmembers of thepopulation.7Rose first described theseemingparadox8 that relatively fewASCVDevents occur in high-risk individuals simply because there are so few high-risk people in the population. The vast majority ofASCVDeventsoccuramong lower-riskpersonsbecause they comprise the greatest portion of the population.9 To prevent manymoreASCVDevents, it is reasonable to considerwhether statin drugs should be used in lower-risk individuals, and whether risk assessment by the new Pooled Cohort Equation leads to a reasonable level of treatment of at-risk people and a rational use of medical resources, even if potentially billions of people worldwide would be recommended for statin drugs.10 In this issue of JAMA, 2 reports suggest that the new risk threshold is likely to be reasonable and cost-effective; it may not even go far enough. If true, even a risk calculator that overestimates risk might be reasonable to use in the clinical setting. In the first report, using FraminghamOffspring Study data, Pursnani et al11 sought to determine whether the 2013 ACC/AHA guidelines improved identification of individuals who developed incident ASCVD, had evidence of coronary artery calcium, or had both compared with the National Cholesterol Education Program’s 2004 Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines. As expected, among 2435 statin-naive people, the new Pooled Cohort Equation led to many more people being eligible for statin therapy (39% for ACC/AHA guidelines vs 14% for ATP III guidelines). However, the newly statin-eligible people were at markedly increased risk for experiencing clinical events, for having elevated levels of coronary calcium, or for having both. These findings offer assurance that the 2013 Pooled Cohort Equation can efficiently and appropriately identify those destined to develop a major ASCVD event in the near future. However, identifying those at risk with reasonable accuracy is only part of the decision-making process. An imporRelated articles pages 134 and 142 Opinion

From the Editorialists: We thank Drs. Soriano and Morera for supporting the National Heart, Lung, and Blood Institute’s (NHLBI’s) recent Strategic Visioning effort to collectively identify the greatest unmet needs in heart, lung, blood, and sleep research (1). They are correct in noting the central role tobacco plays in many diseases that fall within the mission of the NHLBI. We are also grateful to Dr. Jiminez-Ruiz and colleagues from the European Respiratory Society's Tobacco Control Committee for their thoughtful letter and key literature highlighting the importance of strategies for the effective prevention and treatment of tobacco use to foster and preserve human health. The points made in these letters illustrate the kind of feedback we hope to receive from the research community on this and other topics as we move to shape future research priorities. The NHLBI will certainly consider mission-specific compelling questions and critical challenges identified through this process relating to tobacco and its adverse effects on heart, lung, blood, and sleep health. The NHLBI’s new Strategic Visioning forum (http://nhlbistrategicvisioning.ideascale.com/) provides the broad stakeholder community an opportunity to engage in real-time conversations around topics for the NHLBI to address over the next decade, including tobacco and many other important issues. We encourage our communities to actively participate in this novel process to shape our future research directions. We believe that joint efforts by the NHLBI and the research, patient, and provider communities will bring optimal and sustained cardiopulmonary health within reach, with the potential to improve the lives of millions of individuals.