Goal 3: Advance Translational Research

Community Trials for Cardiovascular Health Enhancement

There is a need to initiate innovative community trials that are: theory-based; are integrated multi-component, multi-setting, and multi-level (i.e., they target individual, family, community, and built environment); engage community stakeholders; and use community-participatory research principles to enhance cardiovascular health (CVH) in vulnerable and diverse populations.

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Global impact on cardiovascular health.

Feasibility and challenges of addressing this CQ or CC :

There are smaller scale community interventions but none in the literature that focuses on larger-scale multi-level trials as proposed here. This CQ would target vulnerable and diverse populations to reduce health disparities.

NHLBI supported the stroke belt initiative, and the exemplars in community CV health research: (e.g., the Stanford 5 City Project, The Minnesota Heart Health Program, The Pawtucket Heart Health). The next generation of community CVH research should harness the lessons from these studies, findings for the 8 Americas (Chris Murray), and numerous results from NHLBI cohort studies to implement large-scale community trials for cardiovascular health enhancement.

Resources for a large scale study could be a challenge. Ability to motivate a whole community, to prevent contamination, and to sustain interventions would be a challenge.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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Goal 3: Advance Translational Research

Translation of an intervention to reduce sudden cardiac death

There is a need to identify and to develop pharmaceutical interventions for patients at risk for sudden cardiac death (SCD).

Submitted by (@nhlbiforumadministrator1)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Markedly reduce sudden cardiac death in high populations. Lead to a new pharmacologic paradigm for preventing lethal cardiac arrhythmias.

Feasibility and challenges of addressing this CQ or CC :

Investigators have already demonstrated in animal models of SCD that inhibition of mitochondrial Na/Ca-exchange is associated with a reduction in ventricular arrhythmias and SCD without a change in corrected-QTC.

Using a novel guinea pig model of heart failure and sudden cardiac death (SCD), researchers (Circ Res. 2014 Jun 20;115(1):44-54) have demonstrated that inhibition of the mitochondrial sodium-calcium exchanger prevents SCD. In people, SCD accounts for 170,000 to 450,000 deaths per year in the US. Basic research focused on identifying cardiac ion channel inhibitors have failed to results in antiarrhythmic drugs that prevent SCD. And although clinical research has thus far failed to identify individuals at risk of suffering a SCD in the general population, subpopulations (for example, those with a low ejection fraction months after suffering a myocardial infarction) have been identified that are at high risk. If an effective pharmaceutical intervention was developed that reduces SCD, deaths in these populations would be markedly reduced. Strategies need to be developed to translate this promising basic science finding into saving lives.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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5 net votes
19 up votes
14 down votes
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Goal 4: Develop Workforce and Resources

Establishment of an independent study section on Pulmonary Vascular Biology and Translational Research

The research on pulmonary vascular biology including smooth muscle cell biology and endothelial cell biology and related pulmonary vascular diseases such as pulmonary hypertension and related right heart failure, and endothelial dysfunction in lung vascular inflammation and acute lung injury, as well as pulmonary embolism and lung transplantation has been rapidly expanding. The field is attracting an ever increasing ...more »

Submitted by (@yyzhao)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Establishment of a study section on Pulmonary Vascular Biology and Translational Research will provide adequate funding to stimulate innovative research on this rapidly expanding field and promote translational research and thereby promote human health by providing potential novel therapeutic strategies for the devastating diseases such as pulmonary hypertension and acute lung injury.

Name of idea submitter and other team members who worked on this idea : Youyang Zhao, Kurt Denmark, Asrar B. Malik, Mark Gladwin, Jahar Bhattacharya, Michael Matthay, Sharon Rounds, Jason Yuan

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23 net votes
50 up votes
27 down votes
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Goal 3: Advance Translational Research

Translational research supporting stem cell therapy for cardiovascular disease

Translational research supporting stem cell therapy for cardiovascular disease, including: core laboratories for preclinical IND-enabling studies (e.g., PACT), and clinical trials networks for evaluating promising new treatments (e.g., CCTRN).

Submitted by (@judith.l.bettencourt)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

The most cost effective scientific procedure ever utilized to answer the risk benefit question posed by a new intervention to be used in humans is a clinical trial. Major clinical trials are their most effective when planted in controversial ground (MRFIT, CAST, ALLHAT). Like these studies, which were caught in a controversial dynamic of uncertainties and disparate sets of expectations, a clinical trial network to assess cell therapy is precisely what is needed.

Experienced researchers recognize the current inimical environment of cell therapy. Now - as before - some forces argue that new therapy offers no benefits, while other equally vehement constituents contend that the benefits of therapy are so great, and the risks so small, that the treatment requires little if any regulation and should be available at once to the US public. Each side provides thunder, but little light.

It is precisely in this contentious environment where passions argue beyond the data that clinical trials are required. Their construction of the most objective view of the strengths and weaknesses of the intervention comes at a cost, but the answers these well designed and concordantly executed studies provide is the clearest illuminations of the benefits and risks of human cell therapy.

Feasibility and challenges of addressing this CQ or CC :

Based on the unmet clinical needs in the treatment of cardiovascular disease and the compelling early evidence for the promise of cell therapy, NHLBI created the Cardiovascular Cell Therapy Research Network in 2007. Now in its ninth year, the Network has completed three major clinical trials in cell therapy. It has published 35 manuscripts in prestigious clinical journals including JAMA, Circ, and Circ Research. Its biorepository has published two manuscripts relating baseline phenotype findings to measures of left ventricular function. A fourth clinical trial is underway assessing the effect of cell therapy on peripheral vascular disease. The Network is also proceeding with the largest effort to assess the effect of CSC cells in patients with heart failure - the first clinical trial that will assess the effect of combined cell therapy in heart failure patients. In addition, CCTRN will study the effect of allogeneic mesenchymal stem cells in patients with anthracycline-induced cardiomyopathy. Each of these protocols is NHLBI and FDA approved.

CCTRN’s reputation of conducting and then promulgating the results of high quality clinical trials makes it the most effective mechanism to assess the benefits of cell therapy in cardiovascular disease. It is important to continue to fund the infrastructure already in place to ensure its continued high quality operation and its place as the cornerstone of cardiovascular clinical cell therapy research in the United States.

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115 net votes
149 up votes
34 down votes
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Goal 4: Develop Workforce and Resources

Need to train and nurture more "translators"!

One of the major challenges in translating from bench-to-bedside and back is communication: the ability of basic and clinical scientists to understand each other's scientific language to be able to appreciate the importance of the other’s research questions and findings.

Submitted by (@nhlbiforumadministrator1)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Having an increased number of researchers able to connect dots across the continuum of translational research should increase overall success of translation of ideas into health.

Feasibility and challenges of addressing this CQ or CC :

This requires "rearranging" of already existing elements. Within 5-10 years of running specifically designed re/cross -training programs, the effects might be widely visible.

Basic scientists usually do not keep up with the latest outcomes of important clinical studies, and thus might miss important starting points for new basic research (e.g., negative trials that suggest the need for new hypotheses). The great majority of clinical scientists do not attend basic scientific sessions because are turned off by the specialized (dense/obscure) scientific terms used. Those who are interested in being translators have a hard time integrating and surviving in the "opposite camp" (i.e., at many medical schools, basic scientists are expected to bring in all their salary in a clinical department, and clinicians get little protected time for basic research)

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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22 net votes
39 up votes
17 down votes
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Goal 3: Advance Translational Research

NIH should promote, rather than deter “fast-track” translational research projects

In the current environment, NIH reviewers actually deter, rather than promote, progress on proposed pre-clinical animal research that is most likely to rapidly translate into clinical breakthroughs in the short term. Scientists should be allowed to focus on critical missing information (roadblocks) needed to accelerate a promising treatment to clinical trials. For instance, at the NHLBI there is currently no study section ...more »

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Yes, large animal studies may often be desirable too. But, the comprehensive information needed can be dramatically accelerated by using small rodents (e.g. by increased “n” and shorter lifespan). Then and if necessary, more focused large animal studies can be used more judiciously before commencing human trials. If a proposed, well-designed, translational study has identified a promising new treatment and the PI seeks to collect critical information to set the stage for clinical trials, he/she should be given the chance to conduct this research instead of being directed toward many years of collecting mechanistic data for something that is ready to move toward clinical study. Later, we can prop our feet on the desk and leisurely design those mechanistic studies knowing that more people are surviving, rather than dying. Rome burns while we play!

Feasibility and challenges of addressing this CQ or CC :

Can be done now by simply fast-tracking studies that may truly accelerate improvements in patient outcomes. Knowing that is works is more important than how it works from the patient standpoint.

Name of idea submitter and other team members who worked on this idea : Anthony Martin Gerdes

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9 net votes
18 up votes
9 down votes
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Goal 3: Advance Translational Research

Accelerating Translational Research

NHLBI should define a strategy to promote collaborative research between clinician-scientists who perform patient-oriented research, and basic scientists who focus on the preclinical realm. There is not enough cross-talk between these two groups, and yet much to be gained from increasing interactions between the two (e.g. accelerating the translation of bench science findings into the clinic). In particular, funding strategies ...more »

Submitted by (@golan0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

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2 net votes
2 up votes
0 down votes
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Goal 4: Develop Workforce and Resources

Translational training programs

The strategic vision to enhance translation and to enhance the workforce both require training that spans the scope of basic science, pre-clinical development, clinical trials. We lack coherent mechanisms for training the next generation of translational researchers, some of whom may be MDs, and some PhDs. A program should provide cross-training of Clinical Fellows and Postdocs to reflect the needed interactions between ...more »

Submitted by (@wjones7)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

The impact will trainees with more comprehensive exposure and involvement in translation of science from the bench to bedside. MDs will spend more time in labs or involved in pre-clinical work, PhDs will become CITI certified and assist with enrollment of clinical trials and trial design. Journal clubs will span the sciences, the clinical practice and the translational realm including regulatory and industry considerations. Trainees can use this background whether they go on in medicine, science, translation, or industry to fit and contribute to an increasingly translational medical bioscience field.

Feasibility and challenges of addressing this CQ or CC :

Feasibility must include a academic medicine environment active in translational biomedical science such that the mentors can include scientists, physicians and physician/scientists, some of whom are translators. Some of the scientists should be from industry and perhaps projects and funding can involve industry/Pharm as well these will benefit from an educated workforce. Challenges involve individuals at the sites putting the right teams together, but many Universities are doing this with incubators and translational units at present. This will further the clinical involvement to include Fellows in Fellowship programs in Cardiology, Medicine and Surgery.

Name of idea submitter and other team members who worked on this idea : Keith Jones

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27 net votes
38 up votes
11 down votes
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Goal 2: Reduce Human Disease

Understanding the Genetic & Epigenetic Basis of Congenital Heart Disease?

Over the last thirty years, our fundamental understanding of the genetics and pathogenesis of congenital heart disease has lagged the tremendous advances in the surgical and clinical care of infants with this group of disorders. We need to close this gap with investigation into the genetic basis of congenital heart malformations to develop new models of disease. The goall is translate an improved molecular genetic and ...more »

Submitted by (@jamesr.priestmd)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Congenital heart disease (CHD) is the most common congenital malformation and the most common cause of mortality during the first year of life. Approximately 70% of cases occur sporadically without a strong family history or identifiable genetic syndrome, and the primary heritable basis of most non-syndromic CHD has yet to be identified. Studies of affected kindreds, syndromic disease, and more recently genome wide association studies (GWAS) have shed light on a handful of causal loci, while exome sequencing and studies of structural variation uncovering rare de novo variants in trios have yielded only an 8-10% rate of diagnosis in cohorts with CHD. Despite the application of contemporary techniques and study design to genetic discovery in CHD, the majority of the genetic risk for human cardiac malformations remains unexplained.

Feasibility and challenges of addressing this CQ or CC :

One key challenge is that many of the stakeholders including those affected with congenital heart disease (children), along with the physicians make a diagnosis and referral (obstetricians, neonatologists, general pediatricians), are generally funded by other agencies (NICHD). Trans-agency collaboration and cooperation is necessary to improve the translational research structures necessary to improve disease.

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37 up votes
15 down votes
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Goal 3: Advance Translational Research

Incentivizing Translational Research

Support for scientific research depends on making a compelling case that we contribute to the health of Americans and the health of the US economy. This idea is to address the critical challenge of making basic research relevant to the lives of Americans by incentivizing NHBLI researchers to engage meaningfully in translational research.

Submitted by (@tomtherramus)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

The specific proposal is to give a 5 to 10 percentile bump (similar to that given to junior investigator) to researchers whose NIH funding has led to translational outcomes that are of tangible benefit to the health of Americans and/or the US economy.

 

Categories that would meet the translational bump might include:

1. A clinical trial based on their basic or clinical research;

2. Generation of a device, drug or other therapy that has entered cllinical testing;

3. Granting of a patent that has been licensed by a company,

Name of idea submitter and other team members who worked on this idea : TomT

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16 net votes
25 up votes
9 down votes
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Goal 3: Advance Translational Research

Translational Bioinformatics Spanning Multiple Scales of Biologic Complexity to Implement Precision Pulmonary Medicine at the Po

What translational bioinformatics tools could be used in pulmonary medicine to allow multidimensional, multi-scale modeling of clinical and biomolecular data to assist clinical decision-making?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Deployment of bioinformatics tools to construct multi-dimensional, multi-scale models of pulmonary (mal)functioning from large heterogeneous data sets spanning biological molecules, subcellular compartments, signaling pathways, cells, tissues, organs, organ systems and clinical therapeutics trials to predict actionable precision medicine for clinicians at the point of pulmonary care.

Feasibility and challenges of addressing this CQ or CC :

A variety of existing powerful informatics methods for integrating a vast wealth of clinical and high-dimensional data across DNA to organism compartments to develop multi-scale modeling approaches to improve point-of-care precision medicine. Consistent with a continuous learning healthcare system, precision medicine modeling is recursive, tentative pending better understanding and therefore continuously learning.

Fundamental to implementation of precision medicine is the ability to extract heterogeneous data from basic and clinical research to be integrated systematically into clinical practice in a cohesive and large-scale manner. Deployment of precision medicine models to predict (mal)functioning progression and response the treatment in daily practice relies strongly on the availability of an efficient bioinformatics platform that assists in the translation of basic and clinical science knowledge.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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10 up votes
12 down votes
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Goal 4: Develop Workforce and Resources

Training for radiologist researchers for effective translational research

Critical Challenge

Submitted by (@str0001)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

As targeted therapy and molecular mechanisms of disease are emerging, a mechanism to improve the ability of radiologists to perform translational research is crucial. Such knowledge is essential for collaborative multidisciplinary research that ultimately leads to imaging as disease-specific diagnostic and therapeutic tools to combat pulmonary and cardiovascular disease.

Feasibility and challenges of addressing this CQ or CC :

Knowledge in the molecular mechanisms of disease and the potential for imaging technology to advance via targeted imaging agents, positron emission tomography (PET), functional MR methods, PET/computer tomography, and PET/MR is increasing. The radiologist has in depth expertise within imaging technology, performance of studies, and diagnostic abilities of imaging techniques. A program directed towards developing imagers towards translational imaging research will include in-depth education and training in lung physiology, pulmonary disease mechanisms, multimodality imaging bridging CT, PET/CT, MR and PET/MR, and the molecular techniques. With such knowledge and training, radiologists will be prepared to serve as principal investigators and collaborators in multidisciplinary teams. An understanding of imaging technologies and their capabilities, the clinical challenges, and molecular techniques will enable imagers to provide innovative solutions to diagnostic dilemmas in pulmonary and cardiovascular disease.

Name of idea submitter and other team members who worked on this idea : Society of Thoracic Radiology

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