Goal 3: Advance Translational Research

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

Strategic Goal: Goal 3: Advance Translational Research

Microvascular Dementia

The catchword Alzheimer's Disease (AD) is used to describe almost all types of dementia these days, and a lot of work has gone into developing preventive and/or therapeutic interventions for AD, but studies show that 40% of "AD" patients may in fact have something else. Microvascular Dementia (MD) presents with a similar phenotype. Delineating these two entities and then developing treatment strategies for MD is my ...more »

Submitted by (@wmars0)

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

Details on the impact of addressing this CQ or CC :

Developing therapeutics for AD that target amyloid and/or tau are not going to work on 40% of the population that have incorrectly been diagnosed with AD when they may instead have MD. The compelling question is how to easily delineate the two followed by the challenge of how to treat the population that has MD.

Feasibility and challenges of addressing this CQ or CC :

Accurate diagnostic imaging for true AD (with plaques) is now possible. Therefore, in the presence of cognitive decline, delineating AD versus other entities is now a reasonable, albeit expensive and time consuming, goal. Step one would be to bring costs and time to diagnosis down by developing a less expensive means of testing for true AD versus MD while verifying with the more expensive technologies. The next step would be to determine what contributes to the pathology of MD. For example, is it another type of plaque that is forming (little clots)? Or is the AD plaque injuring the vasculature? Is there genetic predisposition? As far as I know this area is not being explored in depth (other than possibly, the relationship to stroke). Finally, the one could seek to target therapeutics for this particular form of dementia.

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

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Strategic Goal: Goal 3: Advance Translational Research

Best Implementation Strategies

What are the best implementation strategies to improve adherence to clinical practice guidelines, protocols, and other evidence-based practices that actually lead to the elimination of inequities in preventable disability and death from heart, lung, blood, and sleep diseases?

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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Strategic Goal: Goal 3: Advance Translational Research

lipidomics

Although lipidomics research is a growing field of major importance for human health, I have not seen any grant opportunities where it is a focus. This is particularly the case for human/translational research. For example, although some metabolites of fatty acids have been shown in basic science research to be 1000 times more beneficial health than the fatty acids themselves, why is there what appears to be little interest? ...more »

Submitted by (@robertblock)

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

Details on the impact of addressing this CQ or CC :

Such research can expand the implications of personalized medicine

Feasibility and challenges of addressing this CQ or CC :

There are many potential laboratory challenges but they can largely be overcome in the future with improved methods and technologies.

Name of idea submitter and other team members who worked on this idea : Robert C. Block, MD, MPH

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Strategic Goal: Goal 3: Advance Translational Research

The impact of team consultation on COPD outcomes

Does use of periodic and automatic multidisciplinary team consultation improve care and health outcomes of patients with COPD?

Submitted by (@freeborn1956)

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 : John Linnell, COPD Foundation Minnesota State Captain

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Strategic Goal: Goal 3: Advance Translational Research

Translating cardiac development/genetics knowledge into therapy

What is needed to translate our knowledge of cardiac development and congenital heart disease genetics into novel diagnostic and/or therapeutic strategies for congenital or acquired heart disease?

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 new therapies for congenital or acquired heart disease.

Feasibility and challenges of addressing this CQ or CC :

We are poised to take advantage of the incredible advances in our understanding of cardiac development and genetics which have resulted from the development of high throughput technologies.

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

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Strategic Goal: Goal 3: Advance Translational Research

Improving patient-clinician communication and decision-making for patients wiith serious heart, lung or blood diseases

How can we ensure that patients with serious heart, lung, or blood diseases fully understand their prognosis, treatment options, and the risks and benefits of those options and help them make decisions that fully incorporate their own personal values, goals, and treatment preferneces?

Submitted by (@jrc000)

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

Details on the impact of addressing this CQ or CC :

Patients with serious heart, lung and blood diseases are often faced with dificult treatment decisions that involve tradeoffs and long-term consequences without adequate understanding of their prognosis and the risks and benefits of treatment. There is emerging consensus that a shared decision-making approach provides the best support for patients and their families in this situcation, but there is evidence that this is not happening and there is inadequate data to guide the best approach to ensuring it does happen. Dramatic advances in treatment technologies make treatment choices ever more complex and often make the tradeoffs more difficult to fully understand. Advances in our ability to help patients and their families through this decision-making process have not kept up with these advances in treatment options.

Feasibility and challenges of addressing this CQ or CC :

Incorporation of palliative care approaches, decision aides, and improvements in clinician-patient communication provide the opportunity to make important advances in this area, but have not been fully developed or incorporated. There is an opportunity to advance the communication, decision-making, and implementation science to have a dramatic impact on enhancing healthcare and quality of life for patients and thier families.

Name of idea submitter and other team members who worked on this idea : J. Randall Curtis, MD, MPH

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Strategic Goal: Goal 3: Advance Translational Research

Clinical Trial Methodology

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan:

 

Are the current methodologies for clinical trials still the best practices for conducting efficient clinical trials?

Submitted by (@wheeze)

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 : Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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Strategic Goal: Goal 3: Advance Translational Research

Move beyond the use of self-report for dietary intake quantification

There is a need to move beyond the use of self-report for dietary intake quantification towards funding the development of new technology and broader use of objective measures. There is no question that the effects of diet on health, quality of life, and longevity are of great interest to many and plausibly of great importance. Because of that, tremendous research resources have been provided to study this topic. Given ...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 :

Virtually all authors and investigators in this area recognize that such measurements are limited in their validity; the common mantra is that while limited, these methods nevertheless have sufficient validity to merit being used in scientific investigations. In contrast, a growing group of investigators, ourselves included, think that this common mantra is not reasonable. Virtually all authors and investigators in this area recognize that such measurements are limited in their validity; the common mantra is that while limited, these methods nevertheless have sufficient validity to merit being used in scientific investigations. In contrast, a growing group of investigators, ourselves included, think that this common mantra is not reasonable. Instead we believe that the evidence clearly shows that with at least respect to self-reported energy intake, the measurements are so inaccurate that they do not warrant being used as a basis for scientific investigations and conclusions, even when no better measurement is available. Therefore, at least in investigations involving energy intake, we believe that self-report methods should be abandoned for purposes of drawing scientific conclusions about energy intake, and that funds made available for human dietary investigations be directed toward development of new, objective methods and technologies that can replace self-report methods.

Feasibility and challenges of addressing this CQ or CC :

We believe that the scientific community would benefit from development of methods of measuring dietary intake that do not rely upon self-report. We are not recommending that more investment go into refining self-report methods but rather that replacement methods be sought. Some investigators are interested in devices such as smartphone photography as a way of enhancing self-report. It is our intuition that such methods will only be modest enhancements and will be subject to very substantial biases, since they rely on subject cooperation. Instead, we believe that that methods based on principles of physics, engineering, and chemistry (and generally less prone to human filtering/interference) are likely to be more useful in the long run. Investing in such methods could take at least two forms. First, funders could invest in the development of new technologies and techniques. Second, funders could invest in ways that alter the economic conditions for the use of existing techniques, notably doubly-labelled water (DLW). It is remarkable how much the cost of genotyping has decreased in the last several decades, driven by market incentives and a market initially catalyzed by NIH investment. This is not the case with DLW, which has stayed at a fairly constant price for 30 years. We suggest that it may be possible for the NIH to create a market incentive for reductions in price by initially catalyzing a large demand through an infusion of funding for research using DLW.

Name of idea submitter and other team members who worked on this idea : David B. Allison, Ph.D.; Kevin Fontaine, Ph.D.; Kathryn A. Kaiser, Ph.D.; Andrew W. Brown, Ph.D.; Edward C. Archer, Ph.D.

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Strategic Goal: Goal 3: Advance Translational Research

Should Allogeneic stem cell transplantation be considered as an upfront treatment in high risk double hit DLBCL?

Double-hit lymphomas (DHL’s) are high-grade B-cell lymphomas characterized by chromosomal rearrangements of MYC gene with BCL2 and less commonly, BCL6.Large analysis of patients with de novo DLBCL have shown that conventional chemotherapy does not improve the survival of DHL Aggressive upfront chemotherapy followed by autologous stem cell transplantation (ASCT) has become a standard treatment in eligible patients. Retrospective ...more »

Submitted by (@shahram.mori.md)

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 currently no recommendations regarding upfront allogeneic stem cell transplantation of high-risk DHL patients in CR. Harnessing graft versus lymphoma activity may be a potential strategy to improve responses in such patients

Feasibility and challenges of addressing this CQ or CC :

The challenge of this question is the definition of DHL. FISH is commonly used to characterize DHL’s but may miss a significant portion of patients with aggressive disease. Including the cohort DLBCL patients identified by IHC expands the number of patients. Majority of patients with DHL are older but the ability to perform reduced-intensity and haploidentical -transplants will increase the number of eligible patients. The use of post-transplant therapies is needed to keep the lymphoma in check while graft versus lymphoma responses take effect.

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

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Strategic Goal: Goal 3: Advance Translational Research

Advancing translational research requires timely in-depth analysis of large datasets

1. NHLBI investments over the last decade in terms of genomic approaches have yielded many research findings. 2. Rapid analyses of early data identified the "low hanging" fruit (and perhaps some/many important results were missed); this limited the scope of translation (partly because of relatively limited discovery?) 3. Important data are being generated at much greater rate than the data are processed/analyzed thoughtfully. ...more »

Submitted by (@rao000)

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 invest in a few multi-disciplinary data analysis centers (integrating biology with statistical genetics) involving active NHLBI participation (cooperative agreements), the massive amounts of data generated at huge cost could be analyzed more thoughtfully if time and resources are made available. This way, we may be able to identify many more research findings of much greater potential for translation.

Feasibility and challenges of addressing this CQ or CC :

It is feasible to pursue this challenge through cooperative agreements whereby NHLBI scientists can actively participate and ensure that strategic investing is following strategic paths for deep discovery.

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

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Strategic Goal: Goal 3: Advance Translational Research

Adapting interventions for urban, rural and minority populations

Research to adapt evidence-or practice-based interventions for urban, rural and minority populations.

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 : Asthma and Allergy Foundation of America (AAFA)

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Strategic Goal: Goal 3: Advance Translational Research

How can we develop more selective immunosuppression for allogeneic hematopoietic cell transplantation?

Graft versus host disease (GVHD) remains the most significant complication of allogeneic hematopoietic stem cell transplantation (HCT). While the use of HCT has grown significantly safer and has demonstrated broad efficacy in the setting of a broad range of blood diseases, immunosuppressive therapy has not dramatically evolved since the introduction of calcineurin inhibitor-based approaches decades ago. The availability ...more »

Submitted by (@kkomanduri)

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

Details on the impact of addressing this CQ or CC :

GVHD remains a critical problem and major barrier to the more widespread utilization of HCT, especially for nonmalignant diseases, where tolerance of treatment-related mortality is understandably low.

 

There is a compelling need for novel immunosuppressive agents that can effectively limit alloreactivity mediated by donor T and B cells, while relatively sparing pathogen-specific T cells, including those mediating antiviral T cell responses important in the post-HCT interval.

 

In the past decade, drug development has facilitated the introduction into preclinical and clinical trials of a broad range of agents that in addition to targeting pathways of interest in target cells (e.g., aberrant signaling in cancer cells) may also effectively inhibit T and/or B cell responses. Examples include hypomethylating agents (e.g., azacitidine), HDAC inhibitors (e.g., vorinostat), MEK inhibitors (e.g., trametinib) and BTK inhibitors (e.g., ibrutinib). Each of these classes of agents has been demonstrated in preclinical and/or clinical studies to also limit alloreactive T cells, and/or augment regulatory T cell responses, leading to a net reduction of alloreactivity. Unlike traditional agents (e.g., the calcineurin inhibitors) these agents appear to be more selective, and in some cases may have dual benefit in reducing relapse.

 

The NHLBI can facilitate the identification and translation to clinical practice in the setting of HCT trials of novel immunosuppressive agents.

Feasibility and challenges of addressing this CQ or CC :

Research funding targeted to improving the pipeline of novel immunosuppressive agents could have immediate and dramatic impact in the field of HCT, especially impacting its application for nonmalignant diseases. Patients lacking optimal registry donors, especially those from underrepresented minority groups, will particularly benefit from improvements in immunosuppression, as patients receiving less than optimally matched donors are at much higher risk of GVHD.

 

The NHLBI can encourage and facilitate research that tests compounds that have already passed through the drug development process, but in many cases were not intended to function as immunosuppressive agents. Compelling preclinical studies have suggested that targeted inhibition of T and B cells, and/or epigenetic modifiers can lessen alloreactivity while preserving beneficial cellular immune responses and facilitating immune reconstitution.

 

It will be far easier to appropriate therapeutic agents already developed for another purpose than to do novel drug development from scratch. In many cases, preclinical studies have highlighted the therapeutic potential in immunosuppression for agents that have been developed to treat malignancies, but yielded suboptimal success. Research that encourages the development of these drugs as part of a combined immunosuppressive/immunomodulation approach may rescue such compounds, while yielding potential dramatic advances in clinical HCT.

Name of idea submitter and other team members who worked on this idea : Krishna Komanduri, M.D.

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