Goal 4: Develop Workforce and Resources

Bridge “translational gap”

Provide resources and training to improve the ability of scientists to bridge the “translational gap”. Continue and expand the VITA program.

Submitted by (@societyforvascularsurgery)

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

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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5 net votes
7 up votes
2 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 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

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

Infrastructure for human translational research

With the reduction in NCAT support for human translational research, infrastructure support will need to come from the NHLBI. This will increase the cost of most human, mechanistic based RO1 studies by 20-30%. This will exceed the current cap of $500K in many circumstances. The cap will need to be raised or NHLBI and other institutes need to determine how NIH can continue to provide this critical infrastructure.

Submitted by (@gwilliams)

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

Details on the impact of addressing this CQ or CC :

With the pending loss of infrastructure support by NCAT for human translational, mechanistic studies, a contiued decline in resources to support this critical resources for N of 1 studies. With appropriate support there will be increased capacity to determine which pre-clinical data is applicable to humans and to design more percise, mechanism based clinical trials to increase the likelihood of precision, personalized medicine for many of NHLBI's targeted diseases, e.g, hypertension, stroke, cardiovascular disease with diabetes and hypertension, asthma, and sleep apnea.

Feasibility and challenges of addressing this CQ or CC :

The template for addressing this challenge is already available. The specific funding mechanism(s) will need to be addressed.

Name of idea submitter and other team members who worked on this idea : Gordon Williams, Gail Adler, Charles Czeisler, Ellen Seely, Lindsey Baden

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3 net votes
6 up votes
3 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

Translational Research for HIV/AIDS and HLB Health and Diseases

What are the best inroads for the NHLBI to support innovative approaches in the next 5-10 years, especially blood cell therapies based on hematopoietic stem cell and novel gene therapy approaches to control or even cure HIV infection?

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 :

HIV control or possibly even HIV cure could result from developing novel cell therapies, especially hematopoietic stem cell (HSC) transplants, and might also result from early use of antiretroviral therapy in acutely HIV-infected individuals.

• Transplantation of HSC including engineered cells has the potential to eradicate HIV reservoirs for HIV cure: the Berlin patient treated with HSC transplant remains free of HIV and is still the only patient cured of HIV infection as of today;

• Identification of acute HIV infections through routine blood donor screening and early anti-retroviral therapy for identified HIV-infected donors can limit or even prevent the establishment of HIV reservoirs.

Feasibility and challenges of addressing this CQ or CC :

• The Berlin patient has provided the proof of concept that HIV infection can be eradicated, that is, sterilizing cure can be achieved, through HSC transplantation in combination with other therapies;

• Recent studies have shown that early identification of HIV infection and treatment of infected individuals with anti-retroviral therapy as soon as possible can significantly limit the size of the HIV reservoirs even if such early treatment may not be able to completely prevent the establishment of HIV reservoirs; routine blood donor screening for both anti-HIV antibodies and HIV RNA among blood donors offers unique opportunities to identify acute HIV infections.

 

 

For HIV cure, the challenges include:

 

• Generation of HIV-resistant HSCs in adequate quantity for transplantation;

 

• Efficiency of homing and expansion of HIV-resistant HSC transplants;

 

• Efficiency in replacing HIV-infected cells, including CD4+ resting cells as the major HIV reservoirs, with HIV-resistant HSCs following transplantation;

 

• Efficiency in immune reconstitution by HSC transplants;

 

• Safety of HSC transplantation with needed GVHD to eliminate HIV-infected resting T cells while avoiding irreversible damage to the host.

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

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-16 net votes
15 up votes
31 down votes
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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

Voting

-1 net votes
9 up votes
10 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.

Voting

22 net votes
37 up votes
15 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 3: Advance Translational Research

Animal Models for Translational Research and Drug Development

There is a need to identify and develop suitable animal models (e.g. larger, non-primate animal models) that faithfully predict the outcomes of new medicines and treatments in heart, lung, blood, and sleep (HLBS) disorders prior to human clinical trials.

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 :

If animal models can faithfully predict the outcomes in human clinical trials of new medicines and treatments, it will reduce the economic burden for the failure of drug development.

Feasibility and challenges of addressing this CQ or CC :

Identification of current available animal models;

Development of new animal models with recent advances in mammalian genome projects and gene targeting technologies could be done over the next 5-10 years

Medical research, especially in basic discovery, has benefited significantly from the use of various animal models, such as gene-targeted and transgenic mouse models. However, many discoveries from animal models (e.g. mouse models) failed to translate into human applications.

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

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73 net votes
92 up votes
19 down votes
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Goal 3: Advance Translational Research

Improving Drug Safety through Precompetitive Research

The lack of transparency in Pharma clinical studies and the incomplete knowledge of the effect of genetic profiles and pharmacological factors on drug toxicities are challenges in decreasing drug development costs and increasing drug safety.

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 :

Precompetitive research and collaborations directed at improving our understanding of the factors underlying adverse patient responses to investigational heart, lung, blood, sleep drugs will help to expedite the drug development process, increase probabilities of success and reduce product development costs.

Feasibility and challenges of addressing this CQ or CC :

Several public-private initiatives such as The Predictive Safety Testing Consortium and the Cardiac Safety Research Consortium are underway that address components of this problem. NHLBI can join existing initiatives or formulate its own. In either case, NHLBI’s participation as either an honest broker or a funding source will enable substantive progress on several fronts over a 5-10 year period.

Clinical safety complications and chronic exposure toxicities are a major cause of drug trial failures and recalls and thereby contribute to the high cost of pharmaceutical product development and the rising prices of commercial medicines. Safety problems can usually be attributed to the off-target biological effects of drug compounds or their metabolites. Reducing the safety risks associated with drug development will therefore require us to expand our knowledge around the pharmacological and pharmacogenomic factors underlying adverse safety events. Furthermore, adverse events that occur during clinical studies that are conducted by pharmaceutical companies are not usually shared publicly. This lack of transparency contributes to unnecessary inefficiencies and costs in the drug development process.

Mechanisms for minimizing safety hurdles in drug development include funding precompetitive applied research and promoting collaborations among companies to encourage sharing of clinical failure data.

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
17 down votes
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