Thank you for participating!

Thank you to all who contributed to the National Heart, Lung, and Blood Institute (NHLBI) Strategic Visioning Forum. Ultimately, over 1,000 ideas were submitted, with more than 42,000 votes. This remarkable response exceeded expectations and provided a wealth of ideas to draw upon as NHLBI moves forward. Please visit the NHLBI Strategic Visioning page to find out more about the NHLBI Strategic Visioning process.


Welcome to the National Heart, Lung, and Blood Institute (NHLBI) Strategic Visioning Forum. The Institute is gathering ideas for the most compelling scientific priorities in the four NHLBI Strategic Goals to address over the next decade.

Goal 3: Advance Translational Research

Smoking cessation

Smoking cessation

a. Enhance our understanding of the behavioral issues that lead to smoking addiction

b. Explore effective behavioral and pharmacological and non-pharmacological mechanisms to reverse smoking addiction

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

Voting

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

Reduction of transfusion -transmitted CMV infections

Does leukoreduction of cellular blood components reduce transfusion-transmitted Cytomegalovirus (CMV) infection? and 2) Does CMV testing add additional benefit to leukoreduction?

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

Details on the impact of addressing this CQ or CC

CMV is known to be transmitted by cellular blood components. Most cases of CMV infection are asymptomatic but several patient populations, such as very small birth weight neonates, patients undergoing transplantation and patients with other immunodeficiencies, are at risk for life-threatening disease. Despite minimal current high-quality evidence leukoreduction has emerged as an acceptable alternative to provision of CMV-seronegative blood components to reduce the risk of TT-CMV. Different methods of leukoreduction (e.g. Filtration, centrifugation) and risk profiles for patients at risk exist. The data are not available to determine if the transfusion of CMV-seronegative cellular components is equivalent to leukoreduced cellular components to prevent TT-CMV infections these high risk patient populations

Feasibility and challenges of addressing this CQ or CC

There are three major challenges:

  1. Current standard of care varies in different centers and includes: use of CMV seronegative cellular components; use of leukoreduced seronegative cellular components; and both approaches; hence, it may be a challenge to recruit centers to enroll enough patients for a sufficiently-powered RCT.
  2. A very large sample size would be required for an equivalency study given the low frequency of TT-CMV.
  3. The advent of pathogen inactivation, depending on how broadly it is implemented, may reduce the impact of evidence obtained from a RCT comparing CMV sero-testing and leukoreduction.

Name of idea submitter and other team members who worked on this idea Brenda Grossman, Nancy Heddle, John Roback and Aaron Tobian

Voting

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

Multicenter trials of therapies for rare diseases.

Infrastructure for performing research in rare diseases should be enhanced to allow efficient accrual to multicenter 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

Many of the malignant and non-malignant blood diseases that fall under the purview of the NHLBI are uncommon though, in aggregate, important contributors to the burden of disease in the US population. Although in some areas, like blood and marrow transplantation (BMT), there exists an infrastructure for multicenter trials, in many areas there does not. This makes testing potentially effective therapies very difficult. The large increase in the number of national BMT trials following the implementation of that network indicates the effectiveness of the approach, which could be expanded to include cellular therapies and other novel approaches.

Feasibility and challenges of addressing this CQ or CC

The current R01 process does not lend itself to efficient and rapid implementation of trials to test new approaches or to the time needed to complete trials that focus on long-term survival and quality of life endpoints. Even within the existing transplant network, efficiencies could be gained by infrastructural enhancements like a common IRB or government-assisted contracting (i.e., CRADAs), a streamlined process for protocol review (e.g. a one- versus two-step process), etc. Additionally, enhanced ability to collaborate with other organizations or institutes, without undue bureaucratic burden, would allow better use of NIH funds so that more trials could be done.

Name of idea submitter and other team members who worked on this idea Mary Horowitz

Voting

80 net votes
114 up votes
34 down votes
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Goal 2: Reduce Human Disease

Develop and validate a metric to address the full spectrum of patient-level comorbidities affecting critical illness

An individual metric to inform about the additive and not individual impact of comorbidities on critical illness and peri-operative mortality. For instance, we know the impact of COPD or MI or CKD on mortality after hemicolectomy, but not necessarily the additive impact of all three.

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 Society of Critical Care Medicine Executive Committee/Council

Voting

2 net votes
4 up votes
2 down votes
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Goal 1: Promote Human Health

What is the role of the environment in HLB disease etiology

It is clear that genetic sequence variation does not account for a substantial portion of disease burden. It is likely that the broad environment contributes to HLB disease via epigenomic alterations and interaction with genetic variants. There is an urgent need to understand the environmental contribution to disease as most exposures are modifiable and are targets for prevention interventions.

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

Details on the impact of addressing this CQ or CC

Environmental exposures are clear involved in the pathogenesis of asthma, copd, CVD, and stroke. Understanding the environmental contribution may be critical for reducing disease burden for these common diseases.

Feasibility and challenges of addressing this CQ or CC

Interventions to reduce disease burden are highly feasible in the next 5-10 years

Name of idea submitter and other team members who worked on this idea Frank Gilliland

Voting

4 net votes
11 up votes
7 down votes
Active

Goal 2: Reduce Human Disease

What are the biological consequences of sleep loss or disruption and how can they best be avoided?

Arousals in obstructive sleep apena (OSA) are life saving, but the associated disruption of sleep is now thought to cause cognitive impairment, increased risk of high blood pressure and atherosclerosis, as well as glucose intolerance and metabolic syndrome. The mechanisms for these downstream effects, however, are not well understood. Can these specific pathophysiological mechanisms be identified, and can ways for mitigating... 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

By identifying the mechanisms by which sleep loss or disruption affects cognitive, cardiovascular, and metabolic function, we hope to find key regulatory points for which interventions may be developed. For example, if we can allow respiratory reflex responses to reopen the airway without EEG activation during OSA, we may be able to forestall some of the cognitive consequences of inadequate sleep. If we can prevent the autonomic responses associated with the EEG arousals and increases in respiratory drive, we may be able to block the repetiive elevations of blood pressure that lead to long term hypertension and accelerated atherosclerosis. If we can identify the reason for metabolic derangement associated with OSA, we may find, for example, that it is due to circadian misalignment and find ways to realign the sequence of metabolic events with the actual wake-sleep patterns of the patients. Finally, if we can potentiate the respiratory reflexes that re-establish the airway in OSA, without triggering the other components of arousals, we may be able to minimize or prevent the apneas. While current methods for treating OSA (e.g., CPAP and dental appliances) help many people, many others cannot tolerate these devices, and we require additional modes of therapy to mitigate the consequences of OSA.

Feasibility and challenges of addressing this CQ or CC

The methods are currently available to address the questions that are raised above. The revolution in methods for evaluating the functions of neural circuits, using optogenetics and chemogenetics, for example, should allow us to identify brain circuits that are involved in the various components of the reflex responses to apnea. We can examine their neurotransmitters and receptors, and design new therapies based on manipulating CNS circuitry. Methods for assessing ongoing autonomic, respiratory, and metabolic responses in genetically mutated mouse modesl may require further miniaturization of various physiological methods, but this field is also rapidly advancing. Finally, methods for examining ongoing changes in neuronal activity in the living brain of awake mice are rapidly advancing.

Name of idea submitter and other team members who worked on this idea Clifford B Saper, MD, PhD

Voting

96 net votes
125 up votes
29 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

Voting

-18 net votes
8 up votes
26 down votes
Active

Goal 2: Reduce Human Disease

Vasopressin layered on to norepinephrine treatment for septic shock

We know that vasopressin layered on to norepinephrine treatment for septic shock tends to produce better outcomes (VASST trial, Russell et al) than norepinephrine alone. We still need to know if norepinephrine should be first line or if vasopressin should be first line (and perhaps monotherapy) for septic shock.

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

Voting

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

What new methods of platelet preparation, processing, and storage are needed for hemostasis in various clinical conditions?

The limitations of 5-day 22˚ C storage significantly impacts platelet availability. It is critical that we develop new methods of collection, processing, storage to extend the storage time of platelets, and evaluate the use of whole blood. The attributes of these products must be understood to optimally alignment product attributes, clinical efficacy and safety with hemostatic needs in a variety of clinical states. Specifically,... 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

Limitations of current storage methods challenge our ability to meet the increasing demands of cancer chemotherapy and complex surgeries as well as provide platelets to remote areas where trauma frequently occurs. Platelets are transfused to prevent or control bleeding without robust translational or clinical trial evidence of efficacy and safety. In patients with hypoproliferative thrombocytopenia receiving chronic platelet transfusion predominantly for prophylaxis, post-transfusion increments, survival time, and durable hemostatic efficacy are important; however, platelet transfusion alone does not prevent bleeding. The overall state of hemostasis, the endothelium and donor characteristics that affect platelet quality may be important considerations in selecting the best platelet product tailored to individual patients. Better laboratory and clinical measures of platelet function, efficacy and safety are essential for best use of these limited resources. These outcomes should span and link in-vitro testing, animal models, and clinical effects such as thrombotic events, immune, hemostatic, and endothelial effects. Extrinsic, recipient factors (e.g., immune deficiency, platelet or endothelial dysfunction) and intrinsic factors (e.g., donor specific or platelet preparation) should be considered. Systematic analysis of recipients and donors should be broad and include considerations of glycomics, metabolomics, proteomics, genomics, in vivo microscopy, and advanced imaging.

Feasibility and challenges of addressing this CQ or CC

Radiolabeled platelet recovery and survival methods are well established and feasible to perform at several centers within the US. Currently 4-6 million units of platelets and whole blood are transfused per year. It is very feasible to conduct clinical trials that compare methods of platelet preparation, processing, and storage in children and adults who require platelets for either prophylaxis or active bleeding. Multiple research networks that focus on both pediatric and adult transfusion medicine are motivated to perform the pre-clinical and clinical trials required to establish improved efficacy and safety of platelet-containing blood products.

Name of idea submitter and other team members who worked on this idea Terry Gernsheimer, University of Washington, for the 2015 NHLBI State of the Science in Transfusion Medicine

Voting

14 net votes
34 up votes
20 down votes
Active

Goal 2: Reduce Human Disease

Interaction with Office of Rare Diseases

NHLBI should engage more interactively with the Office of Rare Diseases (ORD).

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

Details on the impact of addressing this CQ or CC

There is a synergy that comes with collaboration with rare disease clinical science from other institutes. Some of this synergy is scientific, much of it falls into the support engendered to the patient support groups that are partners in filling the funding gap that many NHLBI initiatives have.

Feasibility and challenges of addressing this CQ or CC

To go it alone in rare disease dissociates the lung disease clinicians from the huge movements in registry science that will impact the field for years to come.

Name of idea submitter and other team members who worked on this idea ATS Member

Voting

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

Biologic mechanisms of prolonged morbidity in survivors of ARDS and sepsis

What are the biologic mechanisms and risk factors that lead to prolonged morbidity in survivors of ARDS and sepsis? What factors during the acute disease phase distinguish patients that recover from those that develop long-term physical, psychological, or cognitive deficits?

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

Details on the impact of addressing this CQ or CC

Reductions in mortality rates for ARDS and sepsis have led to an increase in the number of survivors. Many of these survivors develop new or worsened physical, mental, or cognitive morbidities that persist months or years after hospital discharge. Identifying the biologic mechanisms and risk factors during the acute disease phase that lead to prolonged morbidity could help develop therapies to prevent/treat the long-term morbidities and determine the subgroup of patients that interventions should target.

Feasibility and challenges of addressing this CQ or CC

Research over the past several years has highlighted the increasing number of survivors of ARDS and sepsis that are at risk for long-term physical, psychological, and cognitive impairments. One challenge to answering this question is the limited availability of data and biospecimens of patients with ARDS or sepsis linked to long-term outcomes. Developing a robust resource for this work would require facilitation by NHLBI (potentially in collaboration with other NIH institutes).

Voting

-4 net votes
7 up votes
11 down votes
Active