Goal 3: Advance Translational Research

To facilitate innovation and accelerate research translation, knowledge dissemination, and implementation science that enhances public health.

Goal 3: Advance Translational Research

Lifestyle Interventions for Weight Control

What is the comparative effectiveness in comparison to usual care of scalable alternatives for delivery of evidence-based, comprehensive, lifestyle interventions for weight control that physicians can prescribe to patients either within the primary care setting or by referral within the community? What kinds of infrastructure changes are needed within the primary care setting to increase the effectiveness of these interventions? ...more »

Submitted by (@nhlbiforumadministrator1)

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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41 net votes
73 up votes
32 down votes
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Goal 3: Advance Translational Research

Understanding Chronic Lung Disease Subtypes

What are the subtypes of chronic obstructive lung disease that share a common pathogenesis and can be a basis for precision medicine?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

Chronic Obstructive Pulmonary Disease (COPD) is a complex heterogeneous syndrome. The current approach of regarding this disease as a single entity has limited the ability to develop effective therapies and prevention. Understanding the major subtypes of COPD could lead to more biologically relevant disease classifications, improved prognostic information, and precision medicine treatment.

Feasibility and challenges of addressing this CQ or CC :

The optimal analytical approaches and data types to define complex disease subtypes have not been determined.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and COPDGene Executive Committee

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32 net votes
50 up votes
18 down votes
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Goal 3: Advance Translational Research

Integrating New Genomic Discoveries with Genome Editing Towards Personalized Medicine

The human genome is a veritable digital library of information that includes millions of regulatory elements and the expansive classes of long and short noncoding RNAs. These noncoding sequences represent a rich source of sequence variation (eg, SNPs), but the role such sequence variants play in the control of gene expression or noncoding RNA function is poorly understood. Many noncoding sequence variants will prove to ...more »

Submitted by (@j.m.miano)

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

Details on the impact of addressing this CQ or CC :

We have limited knowledge of the noncoding sequence aspect of the human genome. Defining the full monty of noncoding sequences and their function will provide a more advanced understanding of CV development, homeostasis, and disease. This will be facilitated best by a centralized repository of data modeled after the UCSC Genome Browser. Further, with all functional noncoding sequences in hand, it will be an easy exercise to place, in context, sequence variants that could impact noncoding sequence function. For example, it would be important to know whether a sequence variant in a specific TFBS confers protection or susceptibility to disease. CRISPR-Cas9 could easily model such noncoding sequence variants in cells (and animals) for further exploration of function and responsiveness to intervention. As the cost of WGS continues to fall, more and more genomes will be sequenced with the identification of rare alleles that could have large explanatory power for an individual's CVD and associated treatment responses. Integrating individual genomic data with electronic health data (obviously requiring careful planning and implentation) will, in turn, allow for hypothesis testing based on experimental data accumulating in the centralized database. Ultimately, personalized medicine will be achieved by intersecting patient genomic data with wet lab data that would, in turn, inform the best route of action using CRISPR-Cas9 in patient-derived pluripotent stem cells.

Feasibility and challenges of addressing this CQ or CC :

Developing an interactive and continually updated "Cardiovascular Browser" is certainly feasible. The approach should be much like that taken by the pioneers of the Human Genome Project; that is, all participating labs should make data freely available. The data would include, among other things, expression analysis of noncoding sequences and their relationship to protein-coding genes, regulatory aspects of all coding and noncoding genes in cells of the cardiovascular system and presence of regulatory SNPs, functional annotation of noncoding sequences and sequence variants therein using CRISPR-Cas9 genome editing, and systems biology data that would integrate the accumulating data. Challenges include organizational aspects of a centralized database, appropriate selection of cell types (primary or immortal) and experimental conditions (human cells or animal model?) to capture as much information relating to CVD progression as possible (eg, noncoding sequence expression and function in [a] ECs at disturbed flow regions, [b] SMCs following exposure to oxidized LDL and [c] cardiac myocytes treated with chemotherpy or pressure overload). A challenge with CRISPR-Cas9 continues to be that of inadvertant off target effects (especially in cells). Patient privacy and safeguards against discrimination (eg, insurability) will be key. A board of CV scientists (term limited) and lay persons would thus be needed to develop, implement, and continually revise data management and directions.

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

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6 net votes
16 up votes
10 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

Facilitating the translation of discovery science into proof of concepts in preclinical models

What steps can the research community take to facilitate the translation of discovery science into proof of concepts in preclinical models and in humans for diagnosis, prevention, and treatment? • Current regulatory environment • Lack of communication between discovery and clinical research worlds • Lack of training • Getting industry, academia, and NHLBI to partner; and the business model to make it happen. • Limited ...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 :

• Increased number of novel therapeutics, diagnostics and devices in early phase clinical trials

• Increased impact in rare diseases and unmet needs

• Increased number of licensed IPs from academic centers

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

Voting

17 net votes
25 up votes
8 down votes
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Goal 3: Advance Translational Research

Addressing Health Inequities through Nontraditional Partnerships

What non-traditional partnerships can be leveraged to address health inequities?

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 :

- Broaden reach to underserved populations

- Increase ability to generate evidence based solutions to address health inequities

- Bring expertise and resources to core partner (NIH)

- Enhance ability to identify unanticipated problems and strengthen efforts across all phases of the implementation research agenda

Feasibility and challenges of addressing this CQ or CC :

Feasibility:

- Increased emphasis on health and health inequities by non-profit and particularly, for-profit organizations

- Affordable Care Act (ACA) includes both general and explicit provisions that could narrow the health disparities gaps through implementation research.

- Can leverage and build upon current research partnerships that exist between government agencies and health care delivery systems to address questions of major public health importance

- Opportune time to employ implementation research addressing health inequities through non-traditional research partnership with sectors such as education, state and local government, transportation (built environment), penal and re-entry systems (health risks and disparities), ministries of health, and for-profits, foundations, and non-profits with health care focus.

 

 

Challenges:

 

 

- Risk of disagreements and friction among partners and management with different priorities

 

- Synchronization of timing for decision making

 

- Achieving partners’ concurrence on decisions that provide the most cost effective solutions

 

- Time needed to establish trust among partners that do not routinely partner to address health inequities

 

- There are limited resources dedicated to fostering Public Private Partnerships

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

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6 net votes
19 up votes
13 down votes
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Goal 3: Advance Translational Research

Develop alternatives for patients for whom routine red cell transfusion is unavailable or impractical

There is a compelling need to advance research to understand the physiology governing the safety and efficacy of hemoglobin-based oxygen therapeutics functioning outside the red cell.

Submitted by (@chintamani.atreya)

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

Details on the impact of addressing this CQ or CC :

Adequate numbers of red blood cells are required to sustain human life. Neurocognitive deficits and mortality in acutely anemic humans increase significantly at a hemoglobin level of below 5 g/dL even in the absence of significant cardiovascular disease. At extremely low hemoglobin levels, alternative treatments (supplemental or hyperbaric oxygen, sedation, muscle paralysis and mechanical ventilation) are of only limited benefit and are not without risk. Several classes of patients cannot be routinely transfused with red blood cells. These classes of patients for whom blood is not an option would include patients who will not accept transfusion for religious or personal reasons, patients who due to multiple prior transfusions have developed red cell antibodies without the option for compatible red cells, and massive trauma patients needing treatment in a remote location. The development of cell-free hemoglobin-based oxygen carriers, stable at room temperature and not requiring cross-matching prior to transfusion as a red cell substitute, has been a sought after goal for several decades, yet to date all attempts have met with failure during clinical trials. There is a compelling need to advance research to understand the physiology governing the safety and efficacy of hemoglobin-based oxygen therapeutics functioning outside the red cell.

Feasibility and challenges of addressing this CQ or CC :

Multiple physiologic insults and adverse events seen with earlier modified hemoglobins, compared to banked red blood cells, have been described and are now better, but not completely, understood. Advances in hemoglobin modification could allow for successful use in a variety of clinical scenarios with life-saving results. Additional clinical indications could be investigated and established, such as identification of clinical situations where additional oxygen delivery could modulate the effects of chronic ischemic conditions. In addition, the hemoglobin molecule could be modified to deliver additional therapeutic benefit.

Name of idea submitter and other team members who worked on this idea : Office of Blood Research and Review, CBER, FDA

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8 net votes
13 up votes
5 down votes
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Goal 3: Advance Translational Research

Use isogenic iPS cells to advance Precision Medicine

The goals of Precision Medicine can be achieved if we determine the biological basis of disease-associated variants for NHLBI diseases. Advances in genetic research have yielded hundreds of disease-associated DNA polymorphisms, yet we lack robust methods to experimentally test their functional relevance in human cells. Determining the molecular and cellular basis of human phenotypic variation is one of the great challenges ...more »

Submitted by (@bconklin)

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

Details on the impact of addressing this CQ or CC :

Identifying how disease mutations result in cellular phenotypes will provide an experimental basis for Precision Medicine. Advances in genome engineering and iPS cell technology now offer a unique opportunity for NHLBI researchers to make a focused effort to produce isogenic disease models, to determining the function of putative disease loci. Just a few years ago, the barriers to this type of project seemed insurmountable, as iPS cells were made with damaging DNA insertions, designer nucleases were difficult to make, complex material-transfer agreements (MTAs) inhibited the open sharing of reagents, and cell-engineering methods were cumbersome. Remarkably, all of these barriers have fallen substantially in recent years, to reveal strategic new opportunities. The phenotypes are determined in isogenic human iPS-models, these observations can be applied to animal models, and human clinical studies.

Feasibility and challenges of addressing this CQ or CC :

Progress towards this goal is being made, but slow pace does not meet opportunity that the NHLBI community has. The NHLBI has a much larger opportunity than other institutes because so many genetic variants have already been determined via excellent genetic studies using robust physiological phenotypes. The genetic variants provide hypotheses that are ripe for direct experimental testing in isogenic iPS cell models. Fortunately, many diseases of interest to NHLBI can be modeled in iPS-derived tissues. Other part of NIH (e.g. NIMH, NIDA, NIAAA ) lack abundance of high probability genetic "hits" that NHLBI now has. NHLBI should take advantage of this opportunity.

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

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-19 net votes
8 up votes
27 down votes
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Goal 3: Advance Translational Research

Including subjects with both COPD and asthma in clinical trials

Subjects with both COPD and asthma are typically excluded from clinical trials, but they represent an important segment of the chronic airflow obstruction population. Defining this combination diagnosis is difficult, but requiring a significant smoking history (e.g. 10 pack years), chronic airflow obstruction (GOLD stage 2 or greater after bronchodilator), age > 45, and childhood onset of asthma could identify the relevant ...more »

Submitted by (@nhlbiforumadministrator)

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 : American Thoracic Society member

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

The effectiveness of a protocol-based screening in treating common COPD comorbidities

Does a protocol-based screening for commonly occurring comorbid conditions in patients with COPD (eg. CAD, CHF, depression, sleep apnea) improve management and outcomes for patients with COPD?

Submitted by (@dmcgowan)

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

Details on the impact of addressing this CQ or CC :

Many times co- morbidities are not address appropriately in patients with COPD- a protocol- based screening would support better identification and adherence to guidelines and would improve management and outcomes of individuals with COPD>

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13 net votes
15 up votes
2 down votes
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Goal 3: Advance Translational Research

Generalizing patient education to address co-morbidities

How do we generalize our educational efforts such that multiple co-morbidities and their self-care can be addressed?

Submitted by (@kdeit1946)

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

Details on the impact of addressing this CQ or CC :

Patients with with many co-morbidities, many times have to weigh the benefits of a particular medication for one issue, with the downside of what it may do to another issue. There needs to be much more education in this area.

Name of idea submitter and other team members who worked on this idea : Karen Deitemeyer, COPD Foundation State Captain Program

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

Improving the conduct of cardiovascular clinical trial

There are increasing demands on clinicians for clinical productivity and increasing both clinical and research regulatory requirement. A paralle trend is an increase in clinical trials being conducting outside of US, which is a significant concern in terms of US participation and data applicability to US patients, and the quality of trials data from other regions. These trends have multiple roots spanning from patients ...more »

Submitted by (@javed.butler)

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

Details on the impact of addressing this CQ or CC :

Timely conduct of US relevant data to translate basic science discoveries into either clinical practice or knowing that something is not useful or harmful.

Feasibility and challenges of addressing this CQ or CC :

This will be challenging because it will need public education and advocacy as well as institutional leadership developing incentives and making clinical trials a priority.

Name of idea submitter and other team members who worked on this idea : Javed Butler, MD MPH MBA

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2 net votes
3 up votes
1 down votes
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