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

Need to Determine the Basis for Difference in Response to Weight Management Approaches

Why does the response to weight loss regimen in terms of weight loss and its sustainability, and improvement in health outcomes vary considerably?

Submitted by (@mturner)

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

Details on the impact of addressing this CQ or CC :

Past research focused on using variations of diet and exercise has revealed important information about the health benefits of weight loss. The limitations of such approaches in producing biologically meaningful and sustained weight loss for the majority have also been recognized. Even within a study population, compliance to weight loss regimen, weight loss and its sustainability, and improvement in health outcomes vary considerably. Research is needed to identify the basis for this variation, which may lead to enhanced outcome and applicability of such approaches.

Feasibility and challenges of addressing this CQ or CC :

Identifying factors that enhance weight management response may lead to translational studies that yield more effective results. A strong support of promising clinical translational research may promote a conducive environment for developing more practical applications.

Name of idea submitter and other team members who worked on this idea : The Obesity Society

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8 net votes
14 up votes
6 down votes
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Goal 3: Advance Translational Research

Translation of novel computed tomography technologies

Computed tomography and related x-ray imaging techniques are mainstays of cardiovascular imaging and treatment. Novel technologies are emerging for CT that promise further improvements for cardiovascular disease, such as spectral CT, phase contrast CT or nanoparticle contrast agents. However, many challenges remain for their translation to patients.

Submitted by (@davidcormode)

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

Details on the impact of addressing this CQ or CC :

Spectral and phase contrast CT promise enhanced diagnoses of cardiovascular disease due to their improved soft tissue contrast and increased sensitivity towards contrast agents. Novel contrast agents are starting to allow molecular imaging with CT. These technologies could allow sophisticated characterization of atherosclerotic plaque and other diseases. This would provide enhanced diagnoses, tailored treatments and monitoring of response to therapies.

Feasibility and challenges of addressing this CQ or CC :

Improvements and innovations need to be made in beam filtration, detector systems, electronics and image reconstruction algorithms to allow clinical versions of spectral and phase contrast CT systems to be developed that have similar performance in terms of speed and radiation dose of current clinical systems. Investments need to be made in the development of novel, targeted nanoparticle contrast agent materials and studying their safety prior to clinical trials. While these are very significant challenges, with innovative approaches it should be possible to overcome these problems.

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

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-7 net votes
4 up votes
11 down votes
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Goal 3: Advance Translational Research

Financial and psycosocial impact of transition in sickle cell disease

What are the financial and social implications for individuals living with SCD from adolescence transitioning into adult care? What impact does this transition have on the caregiver and family as a whole?

Submitted by (@sicklecellwarrior)

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

Details on the impact of addressing this CQ or CC :

It is very difficult for many living with SCD to maintain employment (many people have to rely on disability benefits to survive) finish school, even maintain relationships. Greater understanding of the financial and social impact would enable advocacy and direct patient service organizations to better prepare the transitioning population, reducing the financial strain on the individual and the growing medical debt incurred by hospitals and government social service programs.

Name of idea submitter and other team members who worked on this idea : Sickle Cell Warriors, Inc. community members

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30 net votes
38 up votes
8 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

Deriving Cardiac Elements from Pluripotent Human embryonic Stem Cells for Heart Reconstitution

to date, the existing markets lack a clinically-suitable human cardiomyocyte source with adequate myocardium regenerative potential, which has been the major setback in developing safe and effective cell-based therapies for regenerating the damaged human heart in cardiovascular disease.

Submitted by (@xuejunparsons)

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

Details on the impact of addressing this CQ or CC :

Given the limited capacity of the heart for self-repair or renewal, cell-based therapy represents a promising therapeutic approach closest to provide a cure to restore normal heart tissue and function for CVD. There is no evidence that adult stem/precursor/progenitor cells derived from mature tissues, such as bone marrow, cord blood, umbilical cord, mesenchymal stem cells, patients’ heart tissue, placenta, or fat tissue, are able to give rise to the contractile heart muscle cells following transplantation into the heart. Despite numerous reports about cell populations expressing stem/precursor/progenitor cell markers identified in the adult hearts, the minuscule quantities and growing evidences indicating that they are not genuine heart cells and that they give rise predominantly to non-functional smooth muscle cells rather than functional contractile cardiomyocytes have caused skepticism if they can potentially be harnessed for cardiac repair. In recent years, reprogrammed or trans-differentiated adult cells, as a result of being backed by excess sum of government and private funding, have been rekindled as the adult alternates. However, major drawbacks such as abnormal gene expression, accelerated aging, immune rejection, not graftable, and extremely low efficiencies, have severely impaired the utility of reprogrammed or trans-differentiated somatic cells as viable therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

Opportunity: Derivation of pluripotent human embryonic stem cells (hESCs) from the IVF leftover embryos has brought a new era of cellular medicine for the heart. The intrinsic ability of a hESC for both unlimited self-renewal and differentiation into clinically-relevant lineages makes it a practically inexhaustible source of replacement cells for human tissue and function restoration. Therefore, it has been regarded as an ideal source to provide a large supply of functional human cells to heal the damaged or lost tissues that have naturally limited capacity for renewal, such as the human heart and the human brain. Although a vast sum of NHLBI funding has been spent on looking for adult alternates, such as reprogramming and trans-differentiation of fibroblasts or mature tissues, so far, only human cardiac stem/precursor/progenitor cells derived from embryo-originated hESCs have shown such cellular pharmacologic utility and capacity adequate for myocardium regeneration in pharmaceutical development of stem cell therapy for the damaged human heart.

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

Voting

-33 net votes
10 up votes
43 down votes
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Goal 3: Advance Translational Research

ASCVD Risk and Treatment Options

There is little evidence about the best ways in which to effectively communicate atherosclerotic cardiovascular disease (ASCVD) risk to patients so that they clearly understand the potential benefits and harms of treatments in order to make informed decisions about their care. A shift toward shared decision-making and tailored treatment makes it imperative that effective risk communication strategies be developed and ...more »

Submitted by (@nhlbiforumadministrator)

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

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-2 net votes
6 up votes
8 down votes
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Goal 3: Advance Translational Research

Addressing the barriers to the development, adoption of, and adherence to evidence based practices

How do we better understand patient and provider behaviors, as well as health system, community, and socio-cultural factors to effectively address the barriers to the development, adoption of, and adherence to evidence based practices?

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 :

• Higher proportion of people receiving evidence-based care and at goal for that care

• Design better interventions

Feasibility and challenges of addressing this CQ or CC :

• Need for interdisciplinary team science

• Lack of understanding of how personal beliefs and cultural impact on health

• Separation of health care and policy communities

• Payers and politics negatively impacting implementation in health care

• Barriers in accessing insurance and health system databases

• Need engagement, education, and participation of individuals and the public in improving personal and public health and knowledge about the importance of implementation research

• Best practices for recruitment and enrollment

• Current clinical trial structure (need to incentivize ‘soldiers’)

• Need detailed phenotyping within diseases

• Tools to predict non-responders

• Translating best practices of other models (e.g. COG, share clinical trial methodology knowledge)

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

Voting

7 net votes
23 up votes
16 down votes
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Goal 3: Advance Translational Research

T4 Translation Research Informing Early Stage Translational Research

There is a need to utilize insights gained from T4 translation research and implementation science to inform the design and execution of early-stage translational research and 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 :

• Assure that early stage translation research will be suitable for implementation in real world setting

• Aligns the research interventions from T1-T3 research to those appropriate to T4 research

• Potential to focus early stage research in key high burden areas

• Provides research community an understanding of the connections from early stage to late stage translation research which will potentially refine research strategies and directions at all levels

Feasibility and challenges of addressing this CQ or CC :

• Promote the importance of translation to population of heart, lung, blood, and sleep researcher to broader research community

• Potential for more T4 research contributions for guiding investment into translation research from T1-T3

• Provide avenues for T1-T3 investigators to translate their ideas into positive outcomes for population health

• Successful T4 research will stimulate feedback loop and identify opportunities for early translation research

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

Voting

3 net votes
13 up votes
10 down votes
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Goal 3: Advance Translational Research

Interventions to Reduce Low-Value Care

In 2010, the IOM issued a report stating that waste accounted for 30% of health-care spending, or some $750 billion dollars annually, approximately 25 times the annual NIH budget. How can we address and avoid waste and low-value care? Like any complex problem, there are myriad causes and no simple solutions. Defensive medicine, financial incentives, and physician knowledge deficits all contribute and represent potential ...more »

Submitted by (@rollmanbl)

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

Voting

3 net votes
12 up votes
9 down votes
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Goal 3: Advance Translational Research

Why are CHD Mortality Rates Much Higher in United States Than in Japan or Mediterranean Countries?

There remain very substantial unexplained international geographic variations in the incidence of CHD. Japan, for example, and some of the Mediterranean countries have CHD incidence rates for both men and women that are 1/3-1/4 of those in the United States.

Submitted by (@kullerl)

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

Details on the impact of addressing this CQ or CC :

Migrants from these countries have substantial increase in their CHD rates within a very short time after emigration to the United States or to other countries, strongly suggesting that fundamental genetic differences do not account for these variations in the rates. Reduction of the CHD rates in the United States to those in low risk countries will have the most profound effect on CHD and CVD incidence and mortality.

Feasibility and challenges of addressing this CQ or CC :

Research to further evaluate the probable dietary determinants of these extremely low rates and their implications to the United States should be a high priority. This includes careful study of fatty acids, especially polyunsaturated fatty acids, soy proteins, etc., interrelationships with markers of inflammation and inflammatory diseases. Japan, for example, not only has low CHD rates but also low rates of rheumatoid arthritis (RA), chronic obstructive pulmonary disease even in the presence of high levels of cigarette smoking, multiple sclerosis, all of which would suggest that inflammation may be contributing to these variations in risk of disease. Furthermore, there is growing evidence that omega-3 fatty acids and perhaps other fatty acids may play an important role in T cell function and the development of CVD.

Name of idea submitter and other team members who worked on this idea : Lewis H. Kuller, MD, DrPH

Voting

-8 net votes
10 up votes
18 down votes
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Goal 3: Advance Translational Research

Novel Treatments for COPD

COPD is a major health problem leading to 140,000 deaths in the United States. Treatments are supportive, but there is a compelling need for treatments that modify the progression of the disease and that prevent exacerbations. There needs to be a research infrastructure that unites basic, translational, and clinical researchers to develop new approaches. Although this challenge had been met in the past with the now ...more »

Submitted by (@rwise0)

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 : Robert A. Wise

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16 net votes
23 up votes
7 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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