Goal 3: Advance Translational Research

pre-SBIR grant mechanism

SBIR STTR programs currently offer funds to support phase 1 and phase 2 development of translation with corporate involvement. Several here have pointed out that there is need for additional NIH support of investigator initiated translation, and I concur. There is indeed need for early stage and pre-IND support. Such a program would support relatively small grants for proof-of-principle studies, pre-clinical work needed ...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 :

This program would support investigator initiated translational work by supporting pre-clinical proof of principle data before involvement of a company. This would allow for better development of IP, and better developed projects would be more attractive to industry. The work would have to involve some support for project development, so access to regulatory and pharmacological resources and/or consultants to develop the idea could be supported. These could be reviewed by existing SBIR/STTR study sections and funded by the set aside funds.

 

 

 

 

 

A pipeline for investigato-initiated translational science

http://nhlbistrategicvisioning.ideascale.com/a/dtd/74967-32287

Feasibility and challenges of addressing this CQ or CC :

This might be considered a "phase 0" SBIR/STTR and as such would not need to be a large grant (say $150K). These could be used to supplement institutional grants for entrepreneur activity (which are not usually sufficient) for synergy. We have the perfect study sections that already review SBIR/STTRs and funding some of these might impact the SBIR/STTR funding levels, which are fairly generous, but not by much. Would be filling one missing link in the process of funding translation form NIH funded research.

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

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Goal 3: Advance Translational Research

Incentivizing Earlier Investment in NHLBI-Funded Technologies

How might NHLBI assist its awardees to attract private sector funding or partnerships earlier in the product development process to help bridge the gap between academic discoveries and product commercialization?

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 :

Attracting private sector support earlier in the development pipeline would help fill an important funding gap between academic discoveries and product commercialization, enabling products to reach patients more quickly, and improving the return on NHLBI’s investments in basic research.

Feasibility and challenges of addressing this CQ or CC :

Some existing initiatives such as the SBIR Phase IIB Bridge and Small Market Awards encourage non-federal investors to invest earlier in NHLBI-funded technologies. In addition, the NCAI is designed to support critical feasibility studies and business case development to de-risk earlier investment by the private sector. These efforts are showing early signs of success, but impact only a small proportion of NHLBI-funded basic research discoveries.

Estimates for the cost of developing a new drug or device range from the hundreds of millions to billions of dollars and 10-15 years to get from the lab to the patient. The NHLBI cannot fully support that development, so private sector support is critical for biomedical technologies to be commercialized. Overall private capital investment in the life sciences is increasing, but it is not being targeted at heart, lung, blood, and sleep technologies or at the seed stage of development. Venture capital investment in heart, lung, blood, and sleep technologies has declined or remained stagnant since 2008 (http://graphics.wsj.com/venture-capital-and-the-human-body/) and seed stage investment from the private sector for early stage high-risk projects is in short supply (PWC Moneytree: https://www.pwcmoneytree.com/HistoricTrends/CustomQueryHistoricTrend).

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

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Goal 3: Advance Translational Research

The Investigator's Catch-22: How Can NHLBI Help?

The Critical Challenge is to determine how NHLBI can continue to foster the translational research necessary to allow our researchers to further develop their NHLBI-funded basic science discoveries. Researchers can't readily get a "typical" grant to perform the preclinical and early clinical translational IND-enabling research, and also can't yet attract private sector support without having done the work to "de-risk" ...more »

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 :

Ensuring that NHLBI-funded researchers have the means to further develop promising research discoveries will ensure that NHLBI continues to fulfill its Mission. Providing funding or resources to move basic science discoveries from the lab towards the clinic can expand the research environments, opportunities, and collaborations available to NHLBI investigators and lead to potential new therapies for heart, lung, and blood diseases.

Feasibility and challenges of addressing this CQ or CC :

Just as research project itself can take years, if not decades, to accomplish, so too can a cultural shift in our extramural research community. While one may have a different understanding of what constitutes "translational" research depending upon his or her vantage point, in reality it is bi-directional (from bench to bedside and back to bench) and offers possibilities for a wide range of researchers. Engaging established basic scientists in translational research can open new opportunities to them, and younger researchers are likely more familiar and well-poised for new research paradigms and collaborative efforts such as those afforded by the translational development process.

Basic discovery science is appropriately the backbone of the NHLBI extramural research program. But, for any basic science discovery to have a meaningful impact on human health, it must be "translated from the bench to the bedside." These next steps in translation involve a tremendous amount of research that is not amenable to hypothesis-driven grant mechanisms like an R01 or P01. Without access to funding support for early-stage translational work, investigators can be stymied and NHLBI-funded basic science discoveries can languish.

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

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Goal 2: Reduce Human Disease

Fibrosis Care Center Network and Patient Registry

Complex diseases such as interstitial lung disease and pulmonary fibrosis requires a collaborative effort to effectively characterize, appropriately diagnose, and efficient evaluate novel therapies. Similarly, basic, translational and clinical research in this field requires the integration of clinical phenotypes with biologic specimens. We propose the expanded development of the Care Center Network and Patient Registry ...more »

Submitted by (@gcosgrove)

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 envisioned impact of an integrated Care Center Network and Patient Registry is to create a resource that:

 

• Informs the understanding of interstitial lung disease (ILD), its epidemiology and natural history;

• Assists to understand treatment patterns associated with optimal outcomes that will inform an emerging standard of care and development of treatment guidelines;

• Facilitates patient and clinician engagement in support of future prospective studies;

• Furthers study of biomarkers and predictors of disease and severity;

• Documents patient experience of living with ILD as described through patient reported outcomes (PRO) including quality of life, functioning, and symptoms;

• Generates new hypotheses and new endpoints in support of future studies;

• Increases awareness of relevant issues and needs among the immediate ILD community;

• Provides the opportunity to promote and inform policies in the larger health care community in support of those with ILD

Feasibility and challenges of addressing this CQ or CC :

With the establishment of collaborations between several partners, we initiated the PFF Care Center Network and Patient Registry in 2014. The Care Center Network and Patient Registry has since expanded to 21 centers regionally dispersed throughout the United States. The challenges of effectively and efficiently investigating the cause, care and treatment of pulmonary fibrosis are predominantly those of organization and integration of effort. Expertise is present throughout the United States. We suggest that with the continued expansion of the Care Center Network and Patient Registry, those challenges will be overcome and the focus of the fibrosis community efforts can be on diligently investigating the diseases that devastatingly affect patients. An integrated repository of well-phenotyped patients and biologic specimens is the first step in Precision Medicine for patients with interstitial lung disease and pulmonary fibrosis.

Name of idea submitter and other team members who worked on this idea : Gregory P. Cosgrove, MD, The Pulmonary Fibrosis Foundation

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Goal 4: Develop Workforce and Resources

Training of Clinical & Translational Scientists

Although the NCRR and NIGMS used to have a mechanism to train new generation of clinical & translational scientists, this program was stopped. Why?

What is the possibility of other institutes to come up with the priority of funding resources in this regard?

Submitted by (@dkagr0)

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

Details on the impact of addressing this CQ or CC :

In view of the health care models, strong control of insurance companies in determining the remuneration, lack of protective time for qualified clinicians to continue their research, no incentive to the institute for promoting such activities, lack of available tenure-track jobs, pool of effective and well-trained clinical & translational researchers is decreasing rapidly. Even though NIH invests resources to train MD-PhD students, a very minor pool of these graduates continue curiosity and passion in advancing new knowledge and discovering newer approaches.

Feasibility and challenges of addressing this CQ or CC :

1. Additional resources must be developed by NHLBI, NIAID, NIDDK and other major institutes to support this endeavor.

2. Institutes/medical schools who provide protective time to their faculty to continue their efforts in clinical & translational research, must be acknowledged and incentivized.

3. There has been no effective way of measuring outcomes from such investments. All of us must take ownership in utilizing the resources more effectively and more productively.

Name of idea submitter and other team members who worked on this idea : Devendra K. Agrawal, PhD

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Goal 1: Promote Human Health

Transformative Impact of Proteomics

The proteomics field has dramatically progressed over the past 20 years, with advancements and improvements in experimental designs and sample preparation protocols, as well as mass spectrometry equipment, approaches, and analysis. This has resulted in substantial forward progress towards a proteomic pipeline to establish cause and effect mechanisms of cardiovascular disease. There is a need for CV proteomics that resolve ...more »

Submitted by (@mllindsey)

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 necessary tools have been assembled, and managing implementation will reduce the time required for completion of larger scale projects.

Feasibility and challenges of addressing this CQ or CC :

high feasibility; the challenge will be managing communication across groups to maximize impact

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

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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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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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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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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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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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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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