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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.

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.

Rationale : Funding decisions for cardiovascular R01 grant applications at the National Heart, Lung, and Blood Institute (NHLBI) largely hinge on percentile rankings. It is not known whether this approach enables the highest impact science. Objective : Our aim was to conduct an observational analysis of percentile rankings and bibliometric outcomes for a contemporary set of funded NHLBI cardiovascular R01 grants. Methods and Results : We identified 1492 investigator-initiated de novo R01 grant applications that were funded between 2001 and 2008 and followed their progress for linked publications and citations to those publications. Our coprimary end points were citations received per million dollars of funding, citations obtained Conclusions : In a large cohort of NHLBI-funded cardiovascular R01 grants, we were unable to find a monotonic association between better percentile ranking and higher scientific impact as assessed by citation metrics.

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 …

From the Office of Special Projects of the Division of Cardiovascular Sciences (D.G., W.T.-P., A.M.), Office of Science and Technology (M.A.), the Clinical Applications and Prevention Branch of the Division of Cardiovascular Sciences (P.G.K.), and Office of the Director of the Division of Cardiovascular Sciences (M.S.L.) — all at the National Heart, Lung, and Blood Institute, Bethesda, MD. Address reprint requests to Dr. Lauer at 6701 Rockledge Dr., Rm. 8128, Bethesda, MD 20892, or at

Translation of medical evidence into practice has not kept pace with the growth of medical technology and knowledge. We present three case studies – statins, drug eluting stents and bone marrow transplantation for breast cancer – to propose a framework for describing five factors that may influence the rate of adoption. The factors are: validity, reliability and maturity of the science available before widespread adoption; communication of the science; economic drivers; patients’ and physicians’ ability to apply published scientific findings to their specific clinical needs; and incorporation into practice guidelines.

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

Comparative effectiveness research (CER) aims to provide decision makers with the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart, Lung, and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address 8 clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER.

Comparative effectiveness research (CER) is the study of existing treatments or ways to deliver health care to determine what intervention works best under specific circumstances. CER evaluates evidence from existing studies or generates new evidence, in different populations and under specific conditions in which the treatments are actually used. CER does not embrace one research design over another but compares treatments and variations in practice using methods that are most likely to yield widely generalizable results that are directly relevant to clinical practice. Treatments used in transfusion medicine (TM) are among the most widely used in clinical practice, but are among the least well studied. High-quality evidence is lacking for most transfusion practices, with research efforts hampered by regulatory restrictions and ethical barriers. To begin addressing these issues, the National Heart, Lung, and Blood Institute convened a workshop in June 2011 to address the potential role of CER in the generation of high-quality evidence for TM decision making. Workshop goals were to: 1) evaluate the current landscape of clinical research, 2) review the potential application of CER methods to clinical research, 3) assess potential barriers to the use of CER methodology, 4) determine whether pilot or vanguard studies can be used to facilitate planning of future CER research, and 5) consider the need for and delivery of training in CER methods for researchers.

Over the past 50 years, we have seen dramatic changes in cardiovascular science and clinical care, accompanied by marked declines in the morbidity and mortality. Nonetheless, cardiovascular disease remains the leading cause of death and disability in the world, and its nature is changing as Americans become older, fatter, and ethnically more diverse. Instead of young or middle-aged men with ST-segment elevation myocardial infarction, the “typical” cardiac patient now presents with acute coronary syndrome or with complications related to chronic hypertension or ischemic heart disease, including heart failure, sudden death, and atrial fibrillation. Analogously, structural heart disease is now dominated by degenerative valve or congenital disease, far more common than rheumatic disease. The changing clinical scene presents cardiovascular scientists with a number of opportunities and challenges, including taking advantage of high-throughput technologies to elucidate complex disease mechanisms, accelerating development and implementation of evidence-based strategies, assessing evolving technologies of unclear value, addressing a global epidemic of cardiovascular disease, and maintaining high levels of innovation in a time of budgetary constraint and economic turmoil.

In December, 2007, the Congressional Budget Office (CBO) released a report entitled “Research on the Comparative Effectiveness of Treatments.”1 The CBO noted that for many conditions high-quality evidence that can direct clinical care is lacking. The report called for expanded federal efforts in comparativeness effectiveness research (CER), defined as “a rigorous evaluation of the impact of different options that are available for treating a given medical condition for a particular set of patients.” Subsequent to the CBO report, two major pieces of Congressional legislation have stimulated public interest in CER. The American Recovery and Reinvestment Act of 2009 allocated $1.1 Billion to the National Institutes of Health (NIH), the Agency for Health Research and Quality (AHRQ), and the Office of the Secretary for Health and Human Services to fund comparative effectiveness research, and to generate major reports on national priorities in CER. The Affordable Care Act of 2010 established a non-profit nongovernmental “Patient Centered Outcomes Research Institute”2 that will establish and oversee a national research program and attempt to establish methodological standards for CER. While the CBO report and the two Congressional Acts have drawn much attention to CER, such research is not new.3 The NIH and the Veterans Administration (VA) have supported comparative effectiveness research for decades. However, the new national focus on CER has stimulated a number of discussions—and, at times, debates4—on topics such as the need for more high-quality clinical evidence, the attitudes of physicians towards science and evidence-based decision-making,5 the role of economics research in health care,6 and (among the most contentious issues) the complementary roles of observational and experimental research in informing clinical care.7,8 With the advent of the informatics revolution and advances in biostatistical methods, some are asking whether population-based and clinical epidemiology may be in a position to push aside the “gold standard” status traditionally given to randomized trials. Others are more cautious, noting that observational findings have often led to dangerously wrong conclusions.

A few weeks ago Alberts et al published a PNAS Perspective with the attention-grabbing title “Rescuing US Biomedical Research From It Systematic Flaws.”(1) The authors noted that we suffer from “a severe imbalance between the dollars available for research and the still growing scientific community in United States.” At the National Institutes of Health (NIH), we are painfully aware of this, as over the past 10 years we have seen a steady decline in purchasing power, while the number of grant applications has increased and success rates have decreased. In 2000, while the NIH-doubling was still underway, 32% of R01 grant applications were funded; in 2013, that proportion had fallen to 17%.(2)

Late June, 1969, at a suburban Philadelphia day camp. There was much to look forward to: color war, soccer, nature hikes, bug juice, barbecues, swimming, softball, and, of course, no school! But I paid little attention, as for me these paled compared with the upcoming big event, the much-anticipated launch of Apollo 11, the rocket that would fulfill President Kennedy’s call to land men on the moon and bring them back home. During the next few weeks, my parents and I spent hours glued to the TV; and my parents quietly endured the smell of glue emanating from model rockets and lunar modules taking form in my room. Some 20 years later, Bernadine Healy, Director of the National Institutes of Health, called for a moon shot for women’s health. The resulting Women’s Health Initiative (WHI) would be a big science effort that would invest substantial resources, enabling scientists to address questions about hormone replacement therapy, supplementation with Vitamin D and calcium, and diet as interventions that might prevent serious health conditions faced by postmenopausal women. Like National Aeronautics and Space Administration’s moon shot, the National Institutes of Health’s WHI succeeded1; a national team of top-notch scientists enrolled well over 100 000 women into several randomized trials and observational studies. The surprising findings of the relative harms of hormone replacement therapy led to sweeping changes in clinical practice and likely played a role in the past decade’s decline in breast cancer incidence. Now, 25 years later, American science and engineering face an uncertain future. Although big science projects have always generated controversy, shrinking budgets have invited only more criticism. The United States invests a lower proportion of its Gross Domestic Product into research and development than several other economically developed nations.2 Of perhaps greater concern, there has been …

It is essential that the medical profession play a central role in critically evaluating the evidence related to drugs, devices, and procedures for the detection, management, or prevention of disease. Properly applied, rigorous, expert analysis of the available data documenting absolute and relative benefits and risks of these therapies and procedures can improve the effectiveness of care, optimize patient outcomes, and favorably affect the cost of care by focusing resources on the most effective strategies. One important use of such data is the production of clinical practice guidelines that, in turn, can provide a foundation for a variety of other applications, such as performance measures, appropriate use criteria, clinical decision support tools, and quality improvement tools. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guidelines (Task Force) is charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, and the Task Force directs and oversees this effort. Writing committees are charged with assessing the evidence as an independent group of authors to develop, update, or revise recommendations for clinical practice. Experts in the subject under consideration have been selected from both organizations to examine subject-specific data and write guidelines in partnership with representatives from other medical practitioner and specialty groups. Writing committees are specifically charged to perform a formal literature review; weigh the strength of evidence for or against particular tests, treatments, or procedures; and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on efficacy and clinical outcomes constitute …

Alice K. Jacobs, MD, FACC, FAHA, Chair, 2009–2011 Sidney C. Smith, Jr, MD, FACC, FAHA, Immediate Past Chair, 2006–2008 [⁎⁎⁎][1] Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect Nancy Albert, PhD, CCNS, CCRN Christopher E. Buller, MD, FACC[⁎⁎⁎][1] Mark A. Creager, MD, FACC

This document was developed by the American College of Cardiology Foundation (ACCF) Task Force on Clinical Expert Consensus Documents (ECDs) and cosponsored by the American College of Radiology (ACR), American Heart Association (AHA), American Society of Nuclear Cardiology (ASNC), North American

Thanks to the dedicated involvement of the communities it serves, the National Heart, Lung, and Blood Institute (NHLBI) completed development of a scientific working strategic plan in 2007 to guide its activities and initiatives over the next 5 to 10 years.1 The plan outlines a cross-cutting approach that identifies areas in which the NHLBI is well positioned to make major contributions through investigator-initiated research and through programs that enable and supplement investigator-initiated activities. Translational research—both from the bench to the bedside and from the bedside to the community—is strongly and specifically underscored throughout the plan. Here, we summarize NHLBI programs and efforts in translational research. Funding opportunities and early career advice for aspiring researchers have been presented previously in this series.2,3 The ultimate goal of biomedical research is to improve individual and public health by discovering new effective strategies for the maintenance of wellness and for the prevention and treatment of disease. The Institute of Medicine Clinical Research Roundtable identified 2 “translational blocks,” or obstacles, to the realization of tangible health benefits derived from original research.4 The first block, or T1, is “the transfer of new understandings of disease mechanisms gained in the laboratory into the development of new methods for diagnosis, therapy, and prevention and their first testing in humans.” The second block, or T2, is “the translation of results from clinical studies into everyday clinical practice and health decision making.” Some authorities divide T2 into 2 components: T2 includes guideline development, meta-analyses, and systematic reviews, whereas T3 includes dissemination and implementation research.5 Some commentators have argued that the National Institutes of Health (NIH) disproportionately funds T1 compared with T2/T3 and that there is a need for increased national commitments to T2/T3 (from this point referred to as T2).5,6 A recent survey of >3000 …

This document details the procedures and recommendations of the Goals and Metrics Committee of the Strategic Planning Task Force of the American Heart Association, which developed the 2020 Impact Goals for the organization. The committee was charged with defining a new concept, cardiovascular health , and determining the metrics needed to monitor it over time. Ideal cardiovascular health, a concept well supported in the literature, is defined by the presence of both ideal health behaviors (nonsmoking, body mass index 2 , physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and ideal health factors (untreated total cholesterol

The minimal depth of a maximal subtree is a dimensionless order statistic measuring the predictiveness of a variable in a survival tree. We derive the distribution of the minimal depth and use it f...

In July of 2008, the National Heart, Lung, and Blood Institute convened experts in noninvasive cardiovascular imaging, outcomes research, statistics, and clinical trials to develop recommendations for future randomized controlled trials of the use of imaging in: 1) screening the asymptomatic patient for coronary artery disease; 2) assessment of patients with stable angina; 3) identification of acute coronary syndromes in the emergency room; and 4) assessment of heart failure patients with chronic coronary artery disease with reduced left ventricular ejection fraction. This study highlights several possible trial designs for each clinical situation.