Goal 3: Advance Translational Research

Developing a Research Community for T4 Translation Research

What incentives will encourage current and new NHLBI investigators to pursue late translation (T4) research of proven effective interventions in heart, lung, blood, and sleep diseases? One of NHLBI’s current strategic plan’s goals is to translate discovery and early translation research knowledge to late stage T4 translation for use in populations so that it has significant positive health impacts and provides a return ...more »

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 :

A robust global T4 translation research community that will implement proven-effective interventions across populations resulting in a significant positive health impact

Feasibility and challenges of addressing this CQ or CC :

The NHLBI Global Health and Health Inequities Think Tanks identified T4 translation research as an important area that needs development in the very near future.

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

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8 up votes
11 down votes
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Goal 3: Advance Translational Research

Leveraging PEPFAR infrastructure for CVDs

How do we go about leveraging existing infrastructure, such as PEPFAR, to reduce the risk of HLBS diseases among HIV patients and other vulnerable populations? • Common goals and deliverables between NHLBI and partners will need to be identified • The best return on investment of NHLBI funds will need to be determined • Feasible T4 translation interventions in PEPFAR funded studies utilizing HIV populations with HLBS ...more »

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 :

• Decrease the burden of heart, lung, blood, and sleep diseases in studies funded by PEPFAR in HIV populations

• Lessons learned could be expanded to HIV populations outside of Africa

• T4 translation interventions in these populations could help reduce risk factors for heart, lung, blood, and sleep diseases leading to better health outcomes

Feasibility and challenges of addressing this CQ or CC :

• PEPFAR has identified and recruited existing HIV populations in Africa which can be leveraged by NHLBI for heart, lung, blood, and sleep chronic disease research

• Infrastructure that has received PEPFAR investments can also be leveraged to undertake T4 translation interventions

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

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-1 net votes
7 up votes
8 down votes
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Goal 1: Promote Human Health

Adult Cardiomyocytes in Culture

So much basic cardiovascular discovery relies on cell culture models. While cardiac cell lines exist (e.g. HL-1, H9c2), these often poorly model aspects of cardiomyocyte function in-situ (e.g. contractile function, metabolism). In contrast, primary cardiomyocytes isolated from adult animals (especially mice!) are not readily amenable to culture conditions. Even if cells can be kept alive, they are often refractory to ...more »

Submitted by (@paulbrookes)

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

Details on the impact of addressing this CQ or CC :

Addressing this challenge would provide tools for basic researchers to answer many key questions about basic cardiomyocyte function. Removing the "voodoo" element from these methodologies would be an enabling technology. In the neuron field, companies such as "brain bits" will ship tissue with specific protocols, to enable unskilled technicians to culture highly pure neuron subtypes in a matter of hours. Such methods have led to standardized methods in the field, which is good for reproducibility.

Feasibility and challenges of addressing this CQ or CC :

There have been several attempts at keeping adult myocytes alive in culture, using technologies such as electrical pacing, and inclusion of inhibitors in culture media. Likewise some AAV variants are known to transfect hearts in-vivo. However, no uniform widely-accepted methods are used between many different labs. Every lab has their own "trick" to get cells to behave. Many investigators can make a few cells on a dish survive, which is sufficient for single cell work (e.g. microscopy), but getting an entire culture of adult myocytes to survive beyond 24-48 hrs (the minimal time frame needed for genetic manipulations such as siRNA) would open up more common detection and assay measurements. Myocytes from larger animals (e.g. rabbits) are more stable and longer-lived in culture, but such methods do not appear to work for mouse CMs, which therefore precludes application of knockouts and other useful mouse resources.

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

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

Implementation of T4 Translation Research Platforms and Networks

How can cost-effective implementation of late stage translation (T4) research protocols be facilitated for heart, lung, blood, sleep diseases and health inequities?

Can research platforms and networks be created and utilized to facilitate execution of multi-level interventions and approaches for the end user in collaboration with key stake holders?

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 :

Answering this question would lead to timely implementation and dissemination of new knowledge that will be available to address the current heart, lung, blood, sleep health burden.

One of NHLBI’s current strategic plan’s goals is to translate research knowledge for use in populations so that it has significant positive health impacts and provides a return on investment from discovery and early translation research. Currently, only a fraction of new knowledge yielded from proven effective early stage translation research is being used in the real world – resulting in an avoidable disease burden. Late stage translation (T4) research studies the implementation of proven-effective interventions at a multi-level to include populations, communities, healthcare systems, providers, families and patients. Conducting T4 research requires development of comprehensive research teams across communities, public health and health care delivery systems, families, and patients along with unique translation T4 research methods and metrics. Because resource intensive infrastructure is needed to conduct high quality T4 research and this infrastructure is not widely or readily available, a platforms and network for conducting protocols will prove efficient and provide high quality standard outputs.

Feasibility and challenges of addressing this CQ or CC :

The NHLBI Health Inequities Think Tank highly recommended that creating T4 translation research platforms and networks would meet the needs of the scientific community enabling them to respond to the heart, lung, blood, sleep health burden.

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

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4 net votes
13 up votes
9 down votes
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Goal 3: Advance Translational Research

Expand the H3Africa Partnership Model to Decrease HLB diseases

Is there a way to decrease the risks for HLB disease leveraging the H3Africa genomics platform? • Leverage partnerships providing resources to the H3African populations • Identify the best collaborative partners to reach out to the low resource population • Find the best mechanism for collaborations to facilitate the interventions in low resource settings • Merge NHLBI research objectives and goals with those of potential ...more »

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

• Leverage the existing infrastructure (NHLBI & UnitedHealth investment in the Centers of Excellence in Kenya and South Africa; NIH and Wellcome Trust investment in H3Africa) to decrease the burden of HLB using genomics in low resource settings

• Proof of concept: H3African countries & affiliated sites can be used to create a T4 model

• Extension: expand the H3Africa model to other LMICs

Feasibility and challenges of addressing this CQ or CC :

• Existing NHLBI investment in capacity building in some of the H3African countries can be leveraged to address heart, lung, blood, sleep diseases

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

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-6 net votes
6 up votes
12 down votes
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Goal 3: Advance Translational Research

Leveraging big data for T4 translation research

What approaches can help leverage the emerging big data in health and health care for observational and interventional implementation research in heart, lung, blood, sleep diseases?

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 :

• Integration of big data analytics into T4 research study design and interventions development

• Innovative linkages across multiple health and non-health sector data

• Innovative methods to analyze big data linked across sectors

• Various communities are using big data analytics to understand population health data (e.g. electronic medical records s) and opportunities exist for consolidation of these efforts and standardization of methodologies

Feasibility and challenges of addressing this CQ or CC :

• NIH now has focus on big data in its formative stages

• Significant amount of NIH’s budget is/will be dedicated to big data research

• NHLBI can leverage NIH’s investment by foster research in D&I big data analytics and systems science

• Future investment in big data should yield opportunities and focus efforts

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

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0 net votes
16 up votes
16 down votes
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Goal 3: Advance Translational Research

Culturally Specific Preventative research

There are ample research evidence related factors contributing to obesity,type 2 diabetes, cardiovascular disease.The research grant money is diverted heavily on "novel" topic such as genes.The preventative efforts are the key to tackle the issues.Often times,researchers on cardiovascular prevention find it difficult to add novel ideas to convince the grant reviewers in their application.There are many communities here ...more »

Submitted by (@athomas4)

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

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-5 net votes
7 up votes
12 down votes
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Goal 1: Promote Human Health

Functional and high throughput screening assays

There is a need to develop functional assays and high throughput screening to develop probes and potential drug therapies. A. Functional Assays. Researchers face a challenging gap between identifying many sequence variations of potential interest and recognizing which of these variations have a direct functional effect on the physiological system of interest, as opposed to merely being associated with the actual causal ...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 :

Better tools and assays will help develop therapeutics faster and understand basic mechanisms. Improved genes-to-function screens are critical to accelerating the translation of genomic findings, by making screens of genes and variants for altered physiological function faster, cheaper, and more accurate.

Feasibility and challenges of addressing this CQ or CC :

Current technologies and recent NIH pushes for this type of research has investigators and technological advances primed to influence NHLBI disease areas.

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

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-1 net votes
9 up votes
10 down votes
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Goal 2: Reduce Human Disease

Funding Limitations Block Intervention Research

The cap on R01 research grants at $500,000 per year has not changed in over 20 years. In the current fiscal crisis for research it has become an immovable block to submitting intervention studies (randomized clinical trials on treatment). Routine advice from NIH staff is to not even try for a larger study. The cap applies to every year, so one can design a trial that costs less than $2.5 million but exceeds $500,000 in ...more »

Submitted by (@stephen.fortmann)

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

Details on the impact of addressing this CQ or CC :

While it is difficult to argue for increasing funding for anything these days, the $500,000 cap on R01 funding is exerting a perverse bias on research. Very few intervention trials can be accomplished without exceeding this limit in at least one year. This means that trials are limited to those of interest to the NIH staff and to the pharmaceutical industry. Investigators interested in solving therapeutic problems are being force to abandon trials and rely on natural experiments and observational studies, which cannot address all important questions. The natural creativity of the scientific community is being artificially suppressed, distorting the field. The notion that pragmatic trials can substitute for explanatory trials is misplaced. Many unsettled questions cannot be pursued in pragmatic trials, which generally reduce informed consent to a degree to call into question their ethics. It is also unclear that many pragmatic trials can be done under the cap, since they often require extensive work with providers and the healthcare delivery system hierarchy.

Feasibility and challenges of addressing this CQ or CC :

Even a modest change in the cap would be very helpful. Perhaps allowing 1-2 years to be as high as $600,000 without triggering the permission process. Alternatively, the review process for studies exceeding $500,000 could be streamlined if the total does not exceed $2.5 million. Other ways to introduce flexibility are possible. This would allow more ideas to go to review and the staff, who are increasingly deciding which grants get funded, will have more to choose from.

Name of idea submitter and other team members who worked on this idea : Stephen P. Fortmann

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3 net votes
6 up votes
3 down votes
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Goal 4: Develop Workforce and Resources

Training the new generation: not all about “big data” & "omics"

How do we attract more students/trainees into fields that are not popularized by “catchy” names?

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 :

Training the next generation of scientists

Feasibility and challenges of addressing this CQ or CC :

While the need to train the next generation of scientists in emerging fields (e.g. “omics” and “big data”), we should not overlook the need for nurturing “old fashioned” scientists (e.g. physiologists, integrative biologists) which are on the decline.

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

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23 net votes
35 up votes
12 down votes
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Goal 2: Reduce Human Disease

Enhanced Pain Research in Sickle Cell Disease

There is a need for more enhanced pain research in order to help improve sickle cell disease patient outcomes and quality of life.

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

Details on the impact of addressing this CQ or CC :

Pain is the most common clinical manifestation of sickle cell disease (SCD) and accounts for a large proportion of emergency department visits and hospitalizations. Due to its impact on the patients’ quality of life, there is a need for more basic and clinical research studies focused on understanding the mechanisms of different pain syndromes as well as the role of neurotransmitters and inflammation in acute and chronic SCD pain. Also, comparative effectiveness studies in the management of chronic pain will be crucial in helping to improve the patients’ overall quality of life.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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39 net votes
58 up votes
19 down votes
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Goal 4: Develop Workforce and Resources

Develop Vascular Anomalies Medical Training and Research Programs

Patients with vascular anomalies frequently see many physicians and undergo extraneous tests with incorrect diagnoses. A major reason for this is due to the fact that medical training does not include Vascular Anomalies in the syllabus. Thus, many specialties erroneously use the term "hemangioma" for any vascular diagnosis. Over the past 2 decades, there have been major breakthroughs in basic and genetic research, as ...more »

Submitted by (@fblei0)

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

Details on the impact of addressing this CQ or CC :

Developing a training program for vascular anomalies will facilitate improved, more efficient and meaningful patient care. It will also engender collaborative research and data collection for these patients.

Feasibility and challenges of addressing this CQ or CC :

This is very feasible. There are key individuals, advocacy groups, and programs in each of the disease entities - Hemangiomas of infancy, Syndromic Vascular Anomalies (CLOVES, Sturge Weber, Proteus, Maffucci, Klippel Trenaunay, Cutis Marmorata, PTEN Associated Hamartoma Syndrome, Lymphedema Syndromes, etc) which would benefit from a coordinated strategic plan to pool resources, develop a data bank and tissue bank and foster collaborations to move this field forward. This could also serve to develop a network of tiered Vascular Anomalies Programs with certification.

Name of idea submitter and other team members who worked on this idea : Francine Blei, MD

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7 up votes
8 down votes
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