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

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

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 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

Voting

196 net votes
234 up votes
38 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 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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2 net votes
2 up votes
0 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

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

Voting

-4 net votes
13 up votes
17 down votes
Active

Goal 4: Develop Workforce and Resources

Promoting Translational Research training using the R03 mechanism

We in Wisconsin have developed a robust training program for mixed MD and PhD postdocs in a clinical dept and yet their future in research is blocked by few faculty positions, poor funding and over complicated NIH applications. One of the simplest grants is the R03 and we have already had graduates with only a few years postdoc experience succeed in gaining R03 funding. The R03 is a very simple very flexible mechanism. ...more »

Submitted by (@ianbird)

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

Details on the impact of addressing this CQ or CC :

More MD and PhD Postdoc trainees will spend more time focused on work and less writing grants - and the efficiency of expenditures by NIH would go up in terms of paper generated per dollar. MDs who may have a desire to dip in and out of funded research as their clinical path demands would be able to do that. R03 funding does not at any time change your status as a new or early career investigator. Its perfectly reasonable to hold more than one even without a faculty title but as a PhD scientist or practicing clinciian.

Feasibility and challenges of addressing this CQ or CC :

Its easy to do - just decide to do it. Also writing an R03 is the best possible training for writing an R01. I run a T32 for predocs and I mentor K12 postdocs. I know what NIH INTENDS in its training grants. But also recognize just to take on the longer and longer and more demanding K application after already being well trained is a real disincentive to everyone, even if those pages in training plan are well intentioned. IF omeone has not had the chance to train or is cross training to a new area then a K99 is perfect. But someone who is well trained, may stay in their area and has already proven themselves needs a fast submission fast review process to get funding NOW that may be the difference between continued employment though this funding crisis or not. This could provide that for them. Especially with expedited review!

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

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-1 net votes
10 up votes
11 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 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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-12 net votes
10 up votes
22 down votes
Active

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

Voting

23 net votes
50 up votes
27 down votes
Active