Goal 3: Advance Translational Research

Incentivizing Earlier Investment in NHLBI-Funded Technologies

How might NHLBI assist its awardees to attract private sector funding or partnerships earlier in the product development process to help bridge the gap between academic discoveries and product commercialization?

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

Details on the impact of addressing this CQ or CC

Attracting private sector support earlier in the development pipeline would help fill an important funding gap between academic discoveries and product commercialization, enabling products to reach patients more quickly, and improving the return on NHLBI’s investments in basic research.

Feasibility and challenges of addressing this CQ or CC

Some existing initiatives such as the SBIR Phase IIB Bridge and Small Market Awards encourage non-federal investors to invest earlier in NHLBI-funded technologies. In addition, the NCAI is designed to support critical feasibility studies and business case development to de-risk earlier investment by the private sector. These efforts are showing early signs of success, but impact only a small proportion of NHLBI-funded basic research discoveries.
Estimates for the cost of developing a new drug or device range from the hundreds of millions to billions of dollars and 10-15 years to get from the lab to the patient. The NHLBI cannot fully support that development, so private sector support is critical for biomedical technologies to be commercialized. Overall private capital investment in the life sciences is increasing, but it is not being targeted at heart, lung, blood, and sleep technologies or at the seed stage of development. Venture capital investment in heart, lung, blood, and sleep technologies has declined or remained stagnant since 2008 (http://graphics.wsj.com/venture-capital-and-the-human-body/) and seed stage investment from the private sector for early stage high-risk projects is in short supply (PWC Moneytree: https://www.pwcmoneytree.com/HistoricTrends/CustomQueryHistoricTrend).

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

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15 net votes
23 up votes
8 down votes
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Goal 2: Reduce Human Disease

Mechanisms for sex-specific differences in lung diseases

What molecular and cellular pathways explain the sex-specific differences in the prevalence, severity, and progression of lung diseases?

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

Details on the impact of addressing this CQ or CC

Understanding the molecular and cellular bases of differences in prevalence and outcomes of lung diseases will offer insight into disease mechanisms and help to address disease disparities. Some potential bases for disparities, such as differences in hormone levels between men and women, could potentially be therapeutically modulated to mitigate the effects of disease.

Feasibility and challenges of addressing this CQ or CC

The increased understanding of lung cell biology, along with a renewed focus on sex and gender differences, make this the perfect time to start addressing these questions.
Multiple diseases affecting the lung, such as LAM (lymphangioleiomyomatosis), sarcoidosis, asthma, and COPD, have distinct prevalence or associated mortality in a sex-dependent manner. The reasons for these differences are still unknown.

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

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6 net votes
18 up votes
12 down votes
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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 »

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 2: Reduce Human Disease

Prevent cytopenia in septic patients

Sepsis is the leading cause of death in critically ill patients in the USA, affecting particularly young children and the elderly. A hallmark of septic shock patients upon diagnosis is peripheral blood cytopenia. This persistent cytopenia commonly affects myeloid, lymphoid and erythroid lineages resulting in immunosuppression and is a well-established predictor of fatal outcome. Clinical trials targeting the production... more »

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

Details on the impact of addressing this CQ or CC

The current standard-of-care for sepsis patients involves supportive therapy and the early administration of antibiotics, which has been essentially unchanged in 40 years. Therapies that prevent the loss of immune cells are likely to be beneficial to avoid immune suppression and prevent the development of life-threatening systemic infection.

Feasibility and challenges of addressing this CQ or CC

One of the challenges of addressing this question are the large number of biochemical pathways that influence hematopoiesis. Most have not been studied in the context of infection in animal models or in clinical samples. But many animal models and reagents exist that would enable researchers to study this problem. The study of hematopoiesis during infection is feasible and a number of broad questions could be addressed:
a. Do hematopoietic cells and their precursors undergo cell death in response to intracellular pathogens leading to immune suppression?
b. Are hematopoietic cells and their precursors affected by extracellular pathogen-derived products or host-derived molecules resulting from severe injury? Does this lead to cell death and/or prevent the proliferation and differentiation of hematopoietic stem and progenitor cells?
c. How do genetic factors, chronic infection and comorbidities increase the activity of cell death pathways and/or impair the proliferation and differentiation of hematopoietic stem and progenitor cells?

Name of idea submitter and other team members who worked on this idea Ben Croker

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

Development of integrated research teams

There needs to be development of integrated research teams that include clinicians, scientists, engineers, etc.

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 Research Advocacy Committee, American Thoracic Society

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1 net vote
1 up votes
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Goal 4: Develop Workforce and Resources

Supporting early-stage investigators

How can we provide better support for junior investigators who are transitioning from K Award to R Award funding?

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

Details on the impact of addressing this CQ or CC

With the challenging NIH funding climate, many junior investigators are struggling to obtain their first R series grant. Without better support of our junior investigators, the next generation of investigators in academic medicine is in peril.

Name of idea submitter and other team members who worked on this idea Edwin K. Silverman

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281 net votes
313 up votes
32 down votes
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Goal 2: Reduce Human Disease

The potency and safety of transfusable red blood cells

Can we identify approaches to improve potency and/or safety of transfusable RBCs?

42 day pre-transfusion storage of RBCs maximizes utilization, while minimizing waste. However, RBCs undergo changes during collection, manipulation and storage that may reduce their potency or safety. Progress in understanding markers that predict transfusion success at the time of collection and with storage remains slow. New technologies... more »

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

Details on the impact of addressing this CQ or CC

While novel RBC storage methods have been described, the mechanisms underlying their efficacy has not been defined, a step that will be important for further improvements in this area. Some of these methods appear to improve efficacy of the RBC bioenergetic pathways; however, to date there have not been notable advances in reducing cytoskeletal defects common in stored RBCs. The development of new RBC preservation methods that minimize the impact of the storage lesion on specific areas of concern (e.g., diminished oxidation/peroxidation, decreased membrane fragility) is needed.

 

Use of ex vivo generated RBCs is an alternative to conventional donor-derived RBCs which can potentially improve product consistency, reduce the storage lesion, and improve safety. However, advances are needed before this approach is feasible on a large scale. While the development of blood substitutes including blood pharming will likely require more than 3-10 years before it can be ready for the clinic, Blood Pharming from hematopoietic stem/progenitor cells is now technically feasible and the recent development of genome editing methods suggests the exciting possibility of generating GMP compliant “immortal” stem cell sources to produce transfusable RBCs.

Feasibility and challenges of addressing this CQ or CC

Research should include both pre-clinical and clinical studies to define optimal combinations of known factors preserving red cells (e.g. hypo-osmolarity, energy sources, antioxidants), and the development of methods for RBC pathogen reduction that do not increase the storage lesion.

Procedures for generating blood cells from cultured stem/progenitor cells is not currently cost-effective, limiting near term applications to special patient populations such as specific RBC phenotyping of rare donors for chronically transfused patients. Areas of research needed to advance the development of blood substitutes and blood pharming include: (a) new approaches to blood substitutes including artificial oxygen carriers generated from red cell lysates/components or engineered from combinatorial chemico-biological approaches (e.g., derivatization of hemoglobin, encapsidation of modulated oxygen carriers); (b) a better understanding of the biological properties of cultured RBCs with the goal of reducing blood pharming costs; (c) optimizing methods to expand stem cell populations while allowing differentiation to selected clinically relevant blood cell populations at clinically relevant levels; and (d) optimizing methodologies that faithfully replicate embryonic development to develop the cells of interest.

Name of idea submitter and other team members who worked on this idea Nareg Roubinian, MD and Naomi Luban, MD for the NHLBI State of the Science in Transfusion Medicine

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14 net votes
31 up votes
17 down votes
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Goal 2: Reduce Human Disease

Developing approaches to the dissemination of behavioral weight loss programs

The Challenge is to make behavioral weight loss programs readily available to he many overweight and obese patients who need them. Behaivoral weight loss programs are effective in producing weight losses of 7-10% of initial body weight, which has been shown to have major beneficial effects on a number of diseases relevant to NHLBI--including hypertension and sleep apnea. However, at present, these programs are not widely... more »

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

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3 net votes
17 up votes
14 down votes
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Goal 3: Advance Translational Research

Novel extracorporeal devices that remove carbon dioxide

Can novel extracorporeal devices that remove carbon dioxide be tested to limit or avoid positive pressure ventilation in patients with acute respiratory failure from COPD?

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 American Thoracic Society member

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3 net votes
3 up votes
0 down votes
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Goal 2: Reduce Human Disease

Behavioral Science in Asthma Clinical Research

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:

 

Will integration of behavior science in clinical research improve effectiveness of interventions for asthma associated with behavioral risk factors? 

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

Direct thrombin inhibitors and anti-Xa (Ten A) inhibitors in trauma patients - physiologic effects and impact on outcomes

Direct thrombin inhibitors and anti-Xa (Ten A) inhibitors are new, undetectable and irreversible. We have no data on how well these drugs correlate with current measures of coagulopathy such as thromboelastography, or whether antifibrinolytics should be used in patients who are on these drugs. These drugs may increase incidence of traumatic brain injury after minor injury. They are also going to be used increasingly in... more »

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

Details on the impact of addressing this CQ or CC

Understanding pathophysiology of coagulopathy in trauma patients due to these drugs may lead to innovations in management of coagulopathy and help increase our ability to predict/prognostic poor clinical outcomes in patients on these new anticoagulants, detect these drugs in a timely manner and develop antidotes/reversal agents. 

Feasibility and challenges of addressing this CQ or CC

These are eminently feasible with adequate support from the NHLBI. Challenges will be finding collaborations or institutions that have enough clinical volume and adequate basic science/translational research infrastructure to look at these questions seriously.

Name of idea submitter and other team members who worked on this idea Sudha Jayaraman

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-7 net votes
6 up votes
13 down votes
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Goal 2: Reduce Human Disease

Tools for Clinical Research

Clinical trials are at a crossroads. They are too expensive, take too long, and often can't recruit adequately. A critical challenge is to develop tools that can change the cost, time, and recruiting practices for clinical trials.

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

Details on the impact of addressing this CQ or CC

Developing tools to facilitate and streamline the day-to-day performance of clinical trials would help investigators and NHLBI alike. Trials would recruit more quickly, at less cost. We could, therefore, potentially fund more trials. In addition, if we have common templates, this would facilitate a number of things ranging from peer review to IRB submissions, and would also be beneficial to new investigators by providing a framework for them to use.

Feasibility and challenges of addressing this CQ or CC

Some of it will involve 'just doing it' - for example, we have the capability now to require common protocol and informed consent formats. We have sufficient data to develop performance milestones and implement them. The hardest part will be figuring out how to develop pools of patients, or with which organizations to collaborate in order to achieve this. However, 5-10 years should be ample for this and related activities.
For example, we need to emulate and collaborate with other organizations in figuring out how to identify large numbers of patients willing to participate in our trials. We need performance milestones and metrics, and we need tools like common templates for protocols and informed consent forms that all NHLBI-funded trials would use.

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31 net votes
44 up votes
13 down votes
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Goal 2: Reduce Human Disease

Molecular determinants of pulmonary failure in sepsis

Respiratory failure in sepsis is almost universal and leads to worse clinical outcomes, yet it is poorly understood. Recent epidemics of pulmonary failure from respiratory viruses (e.g. influenza, SARS, MERS, etc) makes understanding molecular determinants of respiratory failure and the associated inflammatory and physiologic responses, critical for improving the health of our nation and potentially mitigating future... more »

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

Details on the impact of addressing this CQ or CC

Exploring and understanding the molecular determinants of pulmonary failure will impact not only the predictable complications of acute respiratory illnesses such as influenza, but also inform our understanidng and treatment of myriad other common respiratory illnesses resulting in pulmonary failure, such as pneumonia, chronic obstructive pulmonary disease, asthma, obesity hypoventilation, etc.

Feasibility and challenges of addressing this CQ or CC

Patients receiving critical care services in the United States are among the most close monitored, including continuous monitoring of cardiorespiratory physiology. This highly monitored population is a nature source for studying longitudinal changes in molecular patterns and respiratory physiology.

Name of idea submitter and other team members who worked on this idea Society of Critical Care Medicine Executive Committee/Council

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

Novel Technologies & Clinical Therapeutics

How can NHLBI harness the power of novel technologies involving nucleic acid delivery and gene editing for clinical therapeutics?

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 Cystic Fibrosis Foundation

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-2 net votes
2 up votes
4 down votes
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