Goal 2: Reduce Human Disease

Celiac and Gluten Sensitivity Research

Celiac disease is estimated to effect at least 1% of the population, is a burden on patients & the medical profession & can result in co-morbidities such as cancer, but awareness low--most patients endure a host of health problems for a lifetime unless they are lucky enough to get an early diagnosis. Gluten sensitivity, which can cause many of the same debilitating symptoms, does not have a test, & is also common in the... 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

Reduce disease and increase public health

Feasibility and challenges of addressing this CQ or CC

Finding patients, creating tests

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-7 net votes
4 up votes
11 down votes
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Goal 2: Reduce Human Disease

Alternative treatments in sickle cell disease

There is a growing desire for the development of alternative treatments and natural therapies for the treatment of sickle cell disease.

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

Details on the impact of addressing this CQ or CC

Studies have indicated higher levels of fetal hemoglobin, even moderate levels, as being capable of reducing pain episodes. Development of therapies other than hydroxyurea, may be beneficial to individuals with SCD, specifically natural compounds as opposed to chemical based drugs. Additionally, it may be beneficial to the SCD survivors and the medical community to come up with biomedical alternatives to opiates and heavy narcotics used to induce relief and quiet the discomfort of the patient, even at the risk of addiction, resulting from prolonged usage (a life time).

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

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27 net votes
42 up votes
15 down votes
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Goal 2: Reduce Human Disease

Rare disease therapeutics high throughput screening

Can we develop model systems for the high throughput screening of new and existing agents as possible therapies for rare diseases?

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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-18 net votes
8 up votes
26 down votes
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Goal 2: Reduce Human Disease

Curing Mendelian Disease

Can CRISPR/Cas be utilized to treat human disease? What is necessary to use recent advances in genetic technology, such as CRISPR/Cas, to treat human disease?

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 would inspire the staff, electrify the media, and attract the support needed to complete the task.

Feasibility and challenges of addressing this CQ or CC

The technology has arrived, NHLBI can provide the leadership.
Challenges are many, but surmountable.

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

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3 net votes
13 up votes
10 down votes
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Goal 2: Reduce Human Disease

Is “renewal” of R01 grants, competitive or not, justifiable?

Does NIH intend to develop a new milestone-based grant system and introduce accountability with regards to reaching solid metrics and useful, quantifiable research goals and milestones? Does NIH intend to introduce a truly non-conflicted and independent grant review system, similar to the review system and accountability of the FDA, to increase research efficiency? Should the public be informed annually how effective... 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

Increasing the efficiency of NIH and NHLBI-funded research to the level of a private commercial enterprise, such as major drug development companies do, would be in the best interest of the nation. I am concerned that the current R01-type research grant system has limited focus on innovation and significance. In the current peer review system, fresh ideas can face significant competition from “established investigators” who back their grant applications with data generated during previous research cycles or parallel projects. At present, it appears that most NIH R01-type grant funding has been supporting the generation of data, “knowledge”, research papers, or building research teams and careers rather than projects that propose the development of viable, useful, and potentially feasible solutions to unmet medical needs to serve the public. Moreover, some projects seem to perpetually “fail” and thereby get “renewed”, sometimes for decades without interruption (many of these are run by very “successful” or “established” investigators).

Feasibility and challenges of addressing this CQ or CC

The current system would need to be thoroughly revised and reformed, including the peer review system. It could meet significant resistance from “established” career investigators, including those who produced hundreds of papers but not a single useful innovation that benefits those who pay her.

Name of idea submitter and other team members who worked on this idea Andras Gruber

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-4 net votes
16 up votes
20 down votes
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Goal 3: Advance Translational Research

Infrastructure for human translational research

With the reduction in NCAT support for human translational research, infrastructure support will need to come from the NHLBI. This will increase the cost of most human, mechanistic based RO1 studies by 20-30%. This will exceed the current cap of $500K in many circumstances. The cap will need to be raised or NHLBI and other institutes need to determine how NIH can continue to provide this critical infrastructure.

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

Details on the impact of addressing this CQ or CC

With the pending loss of infrastructure support by NCAT for human translational, mechanistic studies, a contiued decline in resources to support this critical resources for N of 1 studies. With appropriate support there will be increased capacity to determine which pre-clinical data is applicable to humans and to design more percise, mechanism based clinical trials to increase the likelihood of precision, personalized medicine for many of NHLBI's targeted diseases, e.g, hypertension, stroke, cardiovascular disease with diabetes and hypertension, asthma, and sleep apnea.

Feasibility and challenges of addressing this CQ or CC

The template for addressing this challenge is already available. The specific funding mechanism(s) will need to be addressed.

Name of idea submitter and other team members who worked on this idea Gordon Williams, Gail Adler, Charles Czeisler, Ellen Seely, Lindsey Baden

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

Hemostatic treatment with plasma versus 4-factor PCC in the critically ill

For patients in the ICU with coagulopathy and associated World Health Organization (WHO) grade 3 or 4 bleeding, which hemostatic therapy -- plasma versus 4-factor prothrombin complex concentrates -- is preferred?

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

Details on the impact of addressing this CQ or CC

Bleeding is frequently encountered in the ICU and is associated with substantial morbidity and associated mortality. When bleeding occurs, coagulopathy is often present and the optimal coagulation factor management regimen remains a matter of debate. Traditionally (and presently in the US), plasma transfusion has been a cornerstone therapy for the replacement of coagulation factor content in this setting. Moreover, recent evidence supporting the use of plasma in the setting of trauma-related hemorrhage seems to have also generated a renewed enthusiasm for plasma transfusion in other critical care settings.

 

In many locations, there is interest in alternatives to plasma transfusion such as four-factor prothrombin complex concentrates (PCC4) for ICU patients with bleeding. In some locations, factor concentrates have entirely replaced plasma transfusion. However, evidence regarding the benefits and risks of PCC4 versus plasma in ICU patients is lacking. Therefore, we would aim to study the comparative efficacy and risks of a hemostatic strategy relying on PCC4 versus plasma for ICU patients with coagulopathy and bleeding.

Feasibility and challenges of addressing this CQ or CC

Coagulopathy and associated bleeding are common in the intensive care unit environment. Therefore, we believe a multicenter clinical trial evaluating the knowledge gap identified above would be feasible with NHLBI support. Of note, due to the labeled contraindication of disseminated intravascular coagulation for PCC4, such patients would need to be excluded from this trial. Similarly, coagulation abnormalities resulting from congenital coagulation factor deficiencies for which there is a specific coagulation factor product available would also be excluded.

Notably, improved management of coagulopathic bleeding has the potential to impact both clinical outcomes and healthcare resource utilization. Therefore, the outcomes of a trial addressing this knowledge gap would include patient-important outcomes (e.g. mortality, length of hospital stay, bleeding, transfusion-related respiratory complications, thromboembolic complications) as well as outcomes related to healthcare utilization (e.g. product cost, total blood products consumed, interventions required to achieve hemostasis such as surgery or embolization).

Name of idea submitter and other team members who worked on this idea Daryl J. Kor, MD and Walter H. Dzik, MD for the 2015 NHLBI State of the Science in Transfusion Medicine

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28 net votes
43 up votes
15 down votes
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Goal 2: Reduce Human Disease

Reducing Disparities

NHLBI should continue to support prospective cohort studies, projects, and investigators that evaluate longitudinal outcomes in minority populations where longitudinal data are scarce and difficult to obtain. The resources generated remain invaluable and can be used to conduct crosscutting translational research (i.e. the Jackson Heart Study, Strong Heart Study, and others).

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

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1 net vote
2 up votes
1 down votes
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Goal 2: Reduce Human Disease

SLEEP DISORDERS AS A MODIFIABLE RISK FACTOR FOR CHRONIC DISEASE

There is developing evidence that sleep disorders, in particular obstructive sleep apnea and inadequate sleep, can influence the course of other chronic diseases. Observational studies show that CPAP treatment of patients with pre-diabetes who have OSA reduces the incidence of future diabetes. Moreover, animal and human data indicate that insufficient sleep and sleep apnea can affect the rate of progression of neurodegenerative... 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

This question will have considerable impact. Sleep apnea is an independent risk factor for insulin resistance. Moreover, observational studies show that treatment of OSA reduces the rate of future diabetes compared to that which occurs in untreated OSA. Therefore, identifying OSA and treating this could have a profound impact on reducing the rate of diabetes, i.e., a preventative strategy.

Both sleep loss and obstructive sleep apnea have also been shown to be risk factors for subsequent development of Alzheimer’s disease. This has been shown in mouse models and in epidemiological studies to address whether insufficient sleep and sleep apnea are independent risk factors for development of Alzheimer’s disease, in particular accelerating their onset. Determining whether this is so and whether interventions to treat these sleep disorders delay onset of diabetes and Alzheimer’s disease would have profound public health significance.

Feasibility and challenges of addressing this CQ or CC

These disorders are extremely common so that recruitment of subjects is not challenging. Moreover, new technology reduces protocol burden to assess individuals. All studies can be done in the patients’ home. There are existing cohort studies focused on diabetes and the Alzheimer’s Center program that could be used for these studies. Thus, the studies are extremely feasible in the near term.

Name of idea submitter and other team members who worked on this idea Sleep Research Society

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156 net votes
211 up votes
55 down votes
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Goal 2: Reduce Human Disease

Fibrosis Across Organs: Bringing Together Investigators of Fibrosis of the Heart, Lungs and Bone Marrow

Fibrosis can affect essentially any tissue or organ, including the heart, lungs and bone marrow. Effective anti-fibrotic therapy has long been elusive, and transplantation has been the only therapy capable of restoring patient function as fibrotic diseases progress to organ failure. Although these diseases present clinically with organ-specific manifestations, they are now thought to share many common pathogenetic mechanisms.... 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

In the aggregate, diseases characterized by fibrosis have been estimated to account for up to 45% of developed world deaths. Fibrotic diseases addressed by the NHLBI include heart failure with preserved ejection fraction (HFpEF), idiopathic pulmonary fibrosis (IPF), and myelofibrosis (MF), among many others. Each fibrotic disease represents an area of great unmet clinical need, as patients suffer and die with no or limited effective disease-modifying therapies. The impact of developing effective therapies for each of these diseases individually would be great; the impact of developing therapies effective for the entire class of fibrotic diseases across organs would truly be enormous. The clinical burden of HFpEF is staggering – more than 650,000 new patients are diagnosed with heart failure in the US each year, half with diastolic dysfunction. Although not as prevalent, IPF and MF are particularly lethal. IPF has a median survival of approximately three years. MF is arguably the most aggressive of the myeloproliferative disorders and is associated with significantly shortened survival. Although agents such as spironolactone have been unable to treat fibrosis in HFpEF as yet, two anti-fibrotic drugs, pirfenidone and nintedanib, have now been shown to slow progression of IPF, and the oral JAK1/2 inhibitor ruxolitinib has been shown to improve MF survival. These early successes underscore the great impact that developing effective anti-fibrotic therapies will have.

Feasibility and challenges of addressing this CQ or CC

This challenge could be addressed by funding research efforts to identify and therapeutically target fundamental pathogenetic mechanisms shared by fibrotic diseases across organs. Although fibrotic diseases present clinically with organ-specific manifestations, there has been a growing appreciation of that these diseases share many aspects of their pathogenesis. Fibrosis In many of these diseases results from recurrent or non-resolving epithelial or endothelial injury, followed by over-exuberant or aberrant mesenchymal cell responses. Across all organs, these processes result in the pathologic accumulation of fibroblasts and extracellular matrix, with distortion of organ architecture and loss of organ function. Core pathways leading to epithelial and endothelial cell injury and senescence, to fibroblast accumulation and persistence, and to altered matrix biochemical and biomechanical properties, are now being identified. Therapeutics developed to target these core pathways could have broad clinical applicability. Funding initiatives aimed at better the characterization of core fibrotic pathways already identified, the identification of new core fibrotic pathways, and the development of therapies to target core fibrotic pathways, could allow the NHLBI to simultaneously and cost-effectively address the great unmet needs of the large patients with any of the many devastating fibrotic diseases that affect the heart, lungs and bone marrow.

Name of idea submitter and other team members who worked on this idea Andrew M. Tager

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16 net votes
20 up votes
4 down votes
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Goal 2: Reduce Human Disease

Critical Challenge

• One of the most important public health issues the Nation faces is the rising incidence of heart failure. HF incidence rates have risen faster than predicted. The prevalence will increase as better and more therapy becomes available. While heart failure is the biggest ticket item in the Medicare budget, the cost to society will increase more than it has already. But much HF can be prevented or onset prolonged. Investing... 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

See attached file

Feasibility and challenges of addressing this CQ or CC

Critical Challenge

Name of idea submitter and other team members who worked on this idea ASH Officers, Committee Members

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-3 net votes
4 up votes
7 down votes
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Goal 4: Develop Workforce and Resources

What Training Outcomes are Significant?

What trainee outcomes will best fulfill the mission of NHLBI, and what programs best promote these outcomes?

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

Details on the impact of addressing this CQ or CC

A significant number of trainees do not become independent researchers but enter other career paths whose impact on the mission of NHLBI is unclear. A better understanding of the importance of these outcomes and the role of NHLBI-supported training in relation to our mission will inform the implementation and design of training strategies in the future.

Feasibility and challenges of addressing this CQ or CC

OER is rapidly implementing automated approaches to replace the manual tracking of trainees and their subsequent career paths. This effort should facilitate our ability to look specifically at NHLBI-supported programs.
 

Challenge: Obtaining and integrating outcome data that is not included in NIH databases or eRA Commons

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

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-6 net votes
10 up votes
16 down votes
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