Goal 4: Develop Workforce and Resources

Enhance funding for population and public health research

Many challenges posted here focus on increasing translation and development of interdisciplinary teams. Diverse backgrounds and epidemiological training makes population and public health scientists ideal candidates to connect teams in different areas of research around translation to human health. While funding exists specifically for career development of physician and pre-clinical scientists, none exists for epidemiologists. ...more »

Submitted by (@mmongrawchaffin)

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

Details on the impact of addressing this CQ or CC :

NHLBI is currently investing heavily in training epidemiologists at the PhD and postdoctoral level, but may be losing those researchers during the transition to independence and mid-career stages. Compared to those with clinical backgrounds or basic science skills, PhD epidemiologists rarely have alternative resources to fall back on when NIH funding is reduced and may have less interest in joining industry if their primary research interest is improving public health at the population level. This may make epidemiologists particularly vulnerable to leaving the field of health research. Dedicated funding that prioritizes human studies and population level research would help retain well-trained epidemiologists whose primary dedication is to improving chronic disease outcomes.

Feasibility and challenges of addressing this CQ or CC :

While the current level of funding is a challenge to everyone working in science right now, adding funding mechanisms specifically for epidemiology like those that already exist for clinician scientists and pre-clinical research could play an essential role in maintaining the pace of innovation and implementation of research.

Name of idea submitter and other team members who worked on this idea : Morgana Mongraw-Chaffin

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16 net votes
29 up votes
13 down votes
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Goal 3: Advance Translational Research

Advancing the preservation of cellular therapies

Cell therapies are produced in specialized facilities and the viability/function of the cells must be retained in order to permit transportation to the site of use, coordination with patient care, etc. Current options for preserving cells are limited. Conventional methods of cryopreservation may result in poor post thaw function and are difficult to use at the point of care. Liquid storage of cells is typically limited ...more »

Submitted by (@hubel001)

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

Details on the impact of addressing this CQ or CC :

Recent analyses suggest that the pool of patients who could benefit from stem cell-based therapies could be as high as 100 million. The actual number of patients receiving stem cell therapies is actually substantially lower than that (< 500,000). it has been postulated that one reason for the gap between the potential patient pool and the actual patient pool has resulted from poor methods of preservation. The failure of recent clinical trials using mesenchymal stem cells support that hypothesis.

Feasibility and challenges of addressing this CQ or CC :

When developing a cellular therapy, supply chain issues (e.g. preservation) is frequently ignored until the failure of a clinical trial. If preservation issues are addressed concurrently with the development of a cellular therapy, the feasibility of addressing the issue is high.

 

There are two critical challenges to addressing this critical challenge: (1) preservation studies are not considered 'sexy' and therefore score poorly in conventional study sections; and (2) organizations developing a cellular therapy do not have a team member with expertise in preservation.

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

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11 up votes
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Goal 3: Advance Translational Research

Investigator-Initiated Early Translation

What changes are needed to facilitate investigators independently recognizing and pursuing the early translation of their discoveries towards clinical applications through competitive peer reviewed models?

Submitted by (@nhlbiforumadministrator)

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

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

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35 net votes
44 up votes
9 down votes
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Goal 2: Reduce Human Disease

The relationship between genetic variation and disease mechanisms

What is the contribution of individual differences in RNA processing to disease causation, disease modification, disease susceptibility, and positive or negative responses to therapies? Studies using genome sequencing combined with RNA-seq have determined that genetic variation affects regulation of RNA processing as frequently as transcriptional regulation. While transcriptional networks are well defined in heart development ...more »

Submitted by (@tcooper)

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

Details on the impact of addressing this CQ or CC :

There are two areas of impact. First is to develop a better understanding between the effect of genetic variation on RNA processing and how individual differences in RNA processing translate into "phenotype" such as disease causation, disease modification, disease susceptibility, and positive or negative responses to therapies. Genes are filled with cis acting elements that are required for specific patterns of RNA processing. Variation that affects these cis elements are now known to produce different splice variants or mRNAs with different stabilities between individuals. This mechanism translating genotype to phenotype has not been explored. Second is to understand the RNA processing networks as well as we understand transcriptional networks during heart development and in heart disease. This understanding is very likely to provide previously unknown therapeutic approaches and targets.

Feasibility and challenges of addressing this CQ or CC :

The high through put approaches available to compare genome and transcriptome sequences,computational approaches to predict the cis elements for RNA processing, high throughput analysis for RNA binding proteins and RNA structure have provided the tools necessary to perform genome-transcriptome comparisons as a starting point. Current exome/genome analysis ignores the influence of genetic variation in RNA processing. The tools are available. The first challenge is to decide on the question and there are two areas: One- what is the role of RNA processing in heart disease/how can RNA processing be used as a therapeutic target and Two - how much does differences in RNA processing (in addition to transcription) contribute to individual phenotypic differences relevant to disease?

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

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19 net votes
24 up votes
5 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

Developing Methods and Metrics for T4 Outcomes and Impact

How can methods and metrics capable of conducting high quality T4 research be developed to accurately capture outcomes and the overall impact new T4 knowledge has on population health for heart, lung, blood, sleep diseases and disorders?

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 :

High quality T4 research methods and metrics are needed to move the field of T4 translation research forward while linking large data sets from different sources.

Feasibility and challenges of addressing this CQ or CC :

Demand for high quality methods, metric and evaluation of T4 translation research interest is growing and needs to be addressed immediately to move the field forward.

Recent IOM/NRC studies recommended that the NIH and other research funding agencies support the development of more refined analytic methods and study designs for cross-national health research. These methods should include innovative study designs, creative uses of existing data, and novel analytical approaches to better elucidate the complex causal pathways. The T4 field has some specific metrics including acceptability, reach, adoption, appropriateness, feasibility, fidelity, cost, penetration, and sustainability, each with its standard measurement approach. In addition to a rigorous study design, including these metrics along with population level impact direct measures (e.g., morbidity, mortality) and intermediate measures (e.g. blood pressure reduction) will be critical to assess what has been accomplished and to define success. Finally, measuring the overall impact of new knowledge generated from T4 research is challenging because publication bibliometrics of high impact scholarly journals may not fully capture it.

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 3: Advance Translational Research

Translation Research Dissemination & Implementation Frameworks

We need to identify and test the proven effective dissemination and implementation frameworks that are relevant to heart, lung, and blood disorders in order to scale up evidence-based interventions in real world settings, ultimately improving health equity among minority populations, including low income minority residents living in public housing.

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 :

• Ability to determine how much of an evidence based intervention can be sustained in real world settings.

• Add utilization of D&I frameworks to researcher’s core competency training skills.

• Promote long term sustainability of evidence based interventions.

Feasibility and challenges of addressing this CQ or CC :

• Researchers from the 2014 NIH’s Annual Conference on the Science of Dissemination and Implementation: Transforming Health Systems to Optimize Individual and Population Health presented compelling evidence that dissemination and implementation frameworks are an effective means to scaling up evidence based interventions.

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

Genome Editing and Gene Therapy

There is a critical need for the establishment of strategies that will determine the efficacy, safety, and toxicity of genome editing techniques specifically in hematologic diseases.

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

Details on the impact of addressing this CQ or CC :

Inherited monogenic hematologic diseases such as hemophilia, beta-thalassemia and sickle cell disease are prime targets for future application of genome editing technology. However, studies are still needed to advance our understanding of the biology of genome editing as well as determine which other disorders are amenable to genome editing correction. Emphasis on preclinical research that focuses on determining the accuracy, safety and efficiency of this technology in order to help minimize off-target mutations and reduce toxicity, is essential for effective translation of this technology into the clinic. Once preclinical efficacy is established, support will be needed for clinical vector production, toxicity testing of the vectors/reagents used, and the performance of clinical trials. The gene correction strategies developed for inherited disorders will also be attractive for other hematologic diseases, and autoimmune disorders like lupus, rheumatoid arthritis, and type I diabetes). There is also a critical need for supporting preclinical validation studies, scale-up and GMP cell manufacturing, all of which could be shared infrastructures across multiple diseases in the NHLBI portfolio.

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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69 net votes
87 up votes
18 down votes
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Goal 3: Advance Translational Research

Next Stage of COPD Discovery

1) Refinement of COPD subphenotypes for therapeutics, diagnostics and mechanistic interrogation. The NIH should encourage a strong focus on a) rigorous, mechanistically-reinforced definitions (chronic bronchitis, emphysema (with and without obstruction), frequent exacerbators, combined pulmonary fibrosis and emphysema) and 2) the development and optimization of animal model systems that replicate the different subphenotypes. ...more »

Submitted by (@lungmatbio1)

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 we could develop less costly and time consuming cell and animal models of COPD that reflect meaningful subphenotypes, we would be able to not only probe basic mechanism but also have reliable test platforms for candidate therapies.

There is typically a major obstacle between the acquisition of big data from observational disease cohorts, often broad but superficial, and the translation of these findings to basic discovery efforts. The clinical researchers speak a different language than the basic investigators and traversing this chasm with grant enticements might prove helpful.

Feasibility and challenges of addressing this CQ or CC :

This would require some suspension of the classic mechanistic, hypothesis driven proposals to develop these research tools.

There would need to be some reconstruction of study sections to permit these combined clinical-basic grants. The translational PPG was in keeping with this but should be reinforced with smaller grant programs such as RO1 level grants.

Name of idea submitter and other team members who worked on this idea : lungmatbio1

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16 net votes
26 up votes
10 down votes
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Goal 3: Advance Translational Research

Leveraging Networks of Federally Qualified Healthcare Centers

How best do we leverage the existing Federally Qualified Healthcare Center’s (FQHC) infrastructure to study T4 Implementation Research for heart, lung, blood, sleep diseases and conditions among high risk and vulnerable populations?

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 :

• Develop strategies to reduced Health Inequities

• Potentially be scaled up across an entire health system with huge population impact

• Studies would be done in the environment and context where the findings with be implemented leading to better uptake and sustainability.

Feasibility and challenges of addressing this CQ or CC :

• Formative FQHC groups are already being organized but do not have strong leadership and support

• FQHCs have ready access to the high risk and vulnerable populations that would benefit most from the research

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

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7 up votes
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Goal 3: Advance Translational Research

Develop relevant large animal models for various disease conditions

What is the possibility of investing funds primarily in clinically-relevant models where the findings could be translated in to human diseases?

Submitted by (@dkagr0)

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

Details on the impact of addressing this CQ or CC :

Strong emphasis on the use of a clinically-relevant large animal model would hopefully be more productive in developing better therapeutic approaches and management of patients.

Feasibility and challenges of addressing this CQ or CC :

In view of the lack of facility at many institutions and the cost involved, and the rules and regulations by the USDA and other regularity bodies, special emphasis will be required to build the animal facility at an institution. Where will the funds come from? Similar to many other core facilities set up by the NIH at various institutions, what is the possibility of developing specialized centers for testing a new idea in a clinically-relevant large animal facility?

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

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11 up votes
16 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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