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 2: Reduce Human Disease

How can we increase the pharmaceutical clinical research of targeted therapies in pediatric PAH patients, including encouraging

Clinical research, especially randomized pharmaceutical clinical trials, poses many unique challenges compared to research in adult subjects. In pulmonary arterial hypertension, a disease characterized by high blood pressure of the lungs with increased pulmonary vascular resistance leading to right ventricular failure, there are 12 FDA-approved PAH-targeted therapies for adults. None of these medications are currently ...more »

Submitted by (@katherinek)

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

Details on the impact of addressing this CQ or CC :

Pulmonary arterial hypertension is a heterogeneous condition generally characterized by high blood pressure in the lungs and increased pulmonary vascular resistance that leads to right heart failure if left untreated. Though some causes of PAH are seen in both adult and pediatric populations, some etiologies are seen exclusively in pediatric populations, including persistent pulmonary hypertension of the newborn, bronchopulmonary dysplasia, lung hypoplasia, and alveolar capillary dysplasia. Despite these differences in disease etiology, and known physiologic differences in pediatric populations, inhaled nitric oxide (iNO) in the acute setting is the only approved medication for PAH treatment in children. A number of issues have decreased pediatric PAH pharmaceutical research, including protection of the pediatric population as vulnerable subjects, principle of scientific necessity, balance of risk and potential benefit, parental consent/child assent, and feasibility of pediatric clinical trial design and implementation. Encouraging clinical trials of existing adult medications and potentially emerging, novel agents specifically for pediatrics—either through direct sponsorship or regulatory incentives—would not only lead to better outcomes for pediatric PAH patients, but potentially to a better and more comprehensive characterization of the developing pulmonary vascular system and right ventricle.

Feasibility and challenges of addressing this CQ or CC :

Several challenges exist for addressing this critical challenge. First, there are a number of differences between conducting clinical research in pediatric populations compared to adult populations. This not only includes the broad items referenced above, but items as noted by Rose and colleagues related to clinical trial design and analysis including (1) accepted age-matched normal ranges for laboratory values; (2) requirements for the validation of clinical endpoints for the assessment of efficacy and safety; and (3) standards for long-term safety monitoring and pharmacovigilance (Rose K, et al. NEJM 2005). Sponsorship of this type of clinical research is a second concern, which could either be mitigated by direct support from the National Institutes of Health of pediatric PAH clinical trials or in regulatory changes incentivizing pediatric clinical research in rare diseases.

Name of idea submitter and other team members who worked on this idea : Katherine Kroner, Michael Patrick Gray, PHA

Voting

66 net votes
76 up votes
10 down votes
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Goal 2: Reduce Human Disease

Testing PCSK9 Inhibitors

Several inhibitors of PCSK9 are in phase 3 development and show considerable promise for improving the lipid profile; they will be especially appropriate for patients with Familial Hypercholesterolemia and those with statin intolerance. The sponsoring pharmaceutical companies need to complete CVD endpoint trials with full safety testing. However, there may well be more than one drug approved for marketing. The sponsors ...more »

Submitted by (@stephen.fortmann)

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

Details on the impact of addressing this CQ or CC :

Admittedly, this idea is on the mid-range horizon at best, since it will be some years before we know which, if any, PCSK9 inhibitors make it to market. However, if the data produced in phase 3 trials is inadequate to select among marketed drugs, a comparative effectiveness trial would be in order. If the then existing data are compatible with equipoise between the agents, a pragmatic trial design could likely be justified.

Feasibility and challenges of addressing this CQ or CC :

Such a trial would be quite feasible, assuming it is justified by the data.

Name of idea submitter and other team members who worked on this idea : Stephen P. Fortmann

Voting

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

Immunologic Treatment of Hematologic Malignancies

How can the effectiveness of existing curative therapies be improved for allogeneic hematopoietic stem cell transplantation?

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

Details on the impact of addressing this CQ or CC :

Much remains to be understood about immunotherapies in order to facilitate their broad use in the treatment of hematologic disorders. While studies to date have demonstrated significant potential applications, longer-term studies are necessary to further improve the profile of these therapies, including enhancing their overall efficacy while reducing associated toxicities. The efficacy of existing curative therapies can be enhanced by evaluating the mechanisms involved in producing cytokine release syndrome; a condition which has been observed in several patients receiving this therapy. Furthermore, a careful grading scheme to predict toxicity so as to guide the development of preventive and therapeutic strategies is also required. Target identification is another important issue to advance the field. While targeting CD19 appears to be promising, it results in loss of B-cell immunity and requires prolonged immunoglobulin replacement therapies and/or allo-transplantation and new immunologic targets need to be identified in both B cell and T cell malignancies as was as acute and chronic myeloid leukemias. Minimizing the off-tumor target-mediated toxicity of both CAR T-cell and checkpoint blockade therapies would help optimize their utility.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

Voting

43 net votes
63 up votes
20 down votes
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Goal 2: Reduce Human Disease

Cardiac rehabilitation in congenital heart disease

Does cardiac rehabilitation in children with Fontan physiology increase exercise capacity over the long term?

What are the benefits? What is the appropriate dose? What other CHD populations may benefit from cardiac rehabilitation?

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 :

Improve functional capacity and quality of life of patients with congenital heart disease.

Feasibility and challenges of addressing this CQ or CC :

Preliminary data has been promising but larger clinical trials are needed.

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

Voting

-3 net votes
10 up votes
13 down votes
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Goal 1: Promote Human Health

Lung Development Reactivation

What stimuli cause developmental processes to be reactivated in the lung?

Submitted by (@nhlbiforumadministrator1)

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

5 net votes
13 up votes
8 down votes
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Goal 2: Reduce Human Disease

Pulmonary Complications of Sickle Cell Disease - Contribution of Airways Disease

What is the contribution of airways disease to acute and chronic pulmonary distress?

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 :

What is known about this topic:

 

1) Pulmonary function testing is abnormal in 80-90% of kids and 90% of adults with SCD.

 

2) SCD kids with asthma have a higher frequency of ACS and those with a history of ACS have a higher prevalence of asthma.

 

3) An elevated TRV in SCD kids and adolescents may not predict mortality but does predict reduced exercise capacity at 22 months which may be irrespective of pulmonary hypertension

 

4) Dyspnea is extremely common in adults with SCD; 50% of HbSS and 40% of HbSC adults report at least mild dyspnea on exertion. The mechanisms responsible for this are unknown.

 

5) Bronchodilators are often used to treat patients with ACS, yet their benefit is unclear.

 

6) Systemic steroids will increase the rate of rebound pain if used during a vasoocclusive crisis.

 

7) Asthma in SCD is frequently under-treated because of fears associated with systemic and even inhaled corticosteroid use.

Feasibility and challenges of addressing this CQ or CC :

Areas of Controversy:

1) Is there an inter-relationship between airway and vascular disease in SCD?

 

2) Are systemic corticosteroids safe in SCD? Are they indicated in treatment of ACS? Are they indicated for treatment of asthma exacerbations?

 

3) Are inhaled corticosteroids useful in treating or preventing ACS?

 

4) What are the mechanisms responsible for the decline in exercise capacity observed as SCD patients go from late adolescence to early adulthood?

 

5) Will more aggressive treatment of asthma prevent this decline?

 

6) What role does nocturnal hypoxemia and OSA play in disease modulation of SCD?

 

7) What are the mechanisms of the restrictive physiology observed by PFTs primarily in adults?

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

Voting

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

Expanding short term Junior Faculty Training Programs such as the Summer Training Programs for Junior Faculty (PRIDE): More Pgms

Expanding the training efforts (e.g. greater number of funded summer programs, extend training beyond 2 summers, provision for 5-year grants so an additional cohort can be included) would be highly beneficial.

Submitted by (@treva0)

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

Details on the impact of addressing this CQ or CC :

Expand training efforts by increasing number of programs. The PRIDE is now turning away outstanding applicants due to the limited number of training slots across the different program. Since each program is currently training as many scholars as is feasible given their current infrastructure and resources, a solution may include increasing the number of independent programs in the PRIDE or number of trainees a given program can support. This will lead to increasing the number of independent researchers in the health-related fields who come from diverse backgrounds. Flexibility to increase the training period: Some junior faculty need more assistance than others. Some trainees from less research-intensive institutions may have had fewer opportunities to participate in research and thus have less experience and fewer (sometimes no) publications. They would greatly benefit from an initial period dedicated to increasing core research skills and publications prior to proposing and seeking independent grant funds. In the long run, they will be more likely to succeed given the extended training since the PRIDE offers opportunities to collaborate with nationally known researchers and provides access to data resources and the possibility of increasing their publication record. Also, a small percentage of the slots may be reserved for repeat participation in structured manner that provides escalating levels of support.

Name of idea submitter and other team members who worked on this idea : Treva Rice for the PRIDE (Programs to increase diversity among individuals engaged in health-related research): Joe GN “Skip” Garcia, Francisco Moreno Girardin Jean-Louis, Gbenga Ogedegbe, DC Rao, Victor Davila-Roman, Mohamed Boutjdir, Betty Pace, Juan Gonzales, Bettina M Beech, Keith Norris, Marino Bruce, Alicia Fernandez, Kirsten Bibbins-Domingo, and Margaret Handley.

Voting

5 net votes
11 up votes
6 down votes
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Goal 4: Develop Workforce and Resources

Training Support for Non-Research-Intensive Institutions

Institutions that are less research intensive, which may characterize some of the Historically Black Colleges and Universities, Hispanic Serving Institutions and tribal institutions with primarily minority faculty and/or student body, may need additional support for training researchers and for performing both hypothesis driven and student integrated research to provide an environment conducive with NIH efforts to enhance ...more »

Submitted by (@treva0)

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

Voting

-4 net votes
5 up votes
9 down votes
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Goal 3: Advance Translational Research

Implementation Research to Improve Global Availability of Safe Blood Transfusions

What well-developed principles and lessons learned can be employed to improve the safety and availability of blood transfusions in developing countries? The WHO Global Status Report 2013, many research reports, and a recent assessment of burdens of transfusion transmissible infections with HIV, HBV and HCV identified several critical challenges: 1) Significant proportions of blood collections in a large number of countries ...more »

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 :

Significant progress has been made globally in providing adequate supply of safe blood for clinical transfusion thanks to efforts by many, including the US PEPFAR and research supported by NIH such as the REDS programs. Nevertheless, there remains a lack of blood for transfusion and paid blood donations are still collected in many countries. A total of 25 countries were not able to screen all donated blood for one or more of infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis in 2011. As many as 24% of blood donations in low-income countries were not screened following basic quality procedures which include documented standard operating procedures and participation in an external quality assurance scheme. (WHO: Global Status Report 2013). Implementation research to identify cost-effective and sustainable ways to improve blood supplies in the developing world can help reduce blood shortage while enhancing safety by eliminating transfusion transmission of HIV, HBV and HCV.

Feasibility and challenges of addressing this CQ or CC :

Research, including studies supported by the NHLBI REDS, REDS-II, and REDS-III programs, has identified major gaps in global blood supply and reasons for such gaps. International programs, especially PEPFAR, have gained valuable experience implementing quality systems. The time has come to conduct research to optimize the implementation, that is, to find out how to improve global supply of safe blood for transfusion more efficiently in local settings and in a more sustainable manner.

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

Voting

7 net votes
20 up votes
13 down votes
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Goal 4: Develop Workforce and Resources

Increasing Public-Private Partnerships

Given the difficulties of obtaining funding, especially among young investigators, NHLBI should consider public-private partnerships to increase the pool of available opportunities.

Submitted by (@golan0)

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

Voting

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

Expediting Gene and Cell Therapies to the Clinics

What methodologies will best enhance the translation of technologies for gene and cell therapies into potential products for clinical application and commercial development? In considering a strategy for NHLBI investment in gene therapy, it is important to note that we are only at the beginning of a revolution that will eventually impact biomedical research across a broad range of specialties. NHLBI/NIH needs to create ...more »

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 :

Technological advances in vector discovery over the last decade have set the stage for a wave of potential clinical successes in diseases relevant to NHLBI. These advances include the use of lentiviral vectors for bone marrow directed gene therapy with thalassemia emerging as an attractive target and with compelling clinical data with novel AAV serotypes in the treatment of hemophilia B, and possibly hemophilia A in the future.

 

Furthermore, an important milestone was achieved in November 2012 with the approval of the AAV-based product Glybera by the European Medicines Agency for the treatment of a rare form of hypertriglyceridemia. This first and only commercially approved gene therapy product demonstrated regulatory receptivity for gene therapy which fueled a long overdue investment by the biopharmaceutical industry in gene therapy.

Finally, gene editing technologies such as CRISPR (clustered, regularly interspersed short palindromic repeats) are most suited for ex vivo approaches of gene therapy such as those based on engineered bone marrow stems cells for diseases like sickle cell anemia. These types of approaches could substantially reduce the risk of insertional mutagenesis that plagues lentiviral vectors and could improve expression profiles of the corrected cells by utilizing endogenous regulatory sequences.

Feasibility and challenges of addressing this CQ or CC :

It is increasingly being recognized that establishing standardized assays for evaluating product potency and purity such as “pharmacologic” regulation will be critical for the success of gene therapy. NHLBI/NIH can also play a significant role in the development of second generation gene therapy technologies with enhanced safety and efficacy.

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

Voting

66 net votes
97 up votes
31 down votes
Active