Goal 2: Reduce Human Disease

The importance of cosidering sex and gender in presicion medicine

Precision medicine will be invested in across NIH, as per the President's "Precision Medicine Initiative". It is critical that the population base be reflective of the US population, including 50% women. Gender, especially as it relates to exposures, must be a dominant consideration, as these factors are critical to the development of human disease and therefore will be important to prevention.

Submitted by (@pajohnson)

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

Details on the impact of addressing this CQ or CC :

Precision medicine that can be applied accurately to different groups within o our population, in particular women and racial and ethnic minorities.

Feasibility and challenges of addressing this CQ or CC :

Achieving this goal is feasible and essential.

Name of idea submitter and other team members who worked on this idea : Paula Johnson

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2 net votes
2 up votes
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Goal 3: Advance Translational Research

Translational Bioinformatics Spanning Multiple Scales of Biologic Complexity to Implement Precision Pulmonary Medicine at the Po

What translational bioinformatics tools could be used in pulmonary medicine to allow multidimensional, multi-scale modeling of clinical and biomolecular data to assist clinical decision-making?

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 :

Deployment of bioinformatics tools to construct multi-dimensional, multi-scale models of pulmonary (mal)functioning from large heterogeneous data sets spanning biological molecules, subcellular compartments, signaling pathways, cells, tissues, organs, organ systems and clinical therapeutics trials to predict actionable precision medicine for clinicians at the point of pulmonary care.

Feasibility and challenges of addressing this CQ or CC :

A variety of existing powerful informatics methods for integrating a vast wealth of clinical and high-dimensional data across DNA to organism compartments to develop multi-scale modeling approaches to improve point-of-care precision medicine. Consistent with a continuous learning healthcare system, precision medicine modeling is recursive, tentative pending better understanding and therefore continuously learning.

Fundamental to implementation of precision medicine is the ability to extract heterogeneous data from basic and clinical research to be integrated systematically into clinical practice in a cohesive and large-scale manner. Deployment of precision medicine models to predict (mal)functioning progression and response the treatment in daily practice relies strongly on the availability of an efficient bioinformatics platform that assists in the translation of basic and clinical science knowledge.

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

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-2 net votes
10 up votes
12 down votes
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Goal 3: Advance Translational Research

Efficient Evidence-Based Practice

How can we most efficiently utilize limited resources/manpower to facilitate adherence to evidence-based practices and enhance public health?

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

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

Improving heart, lung, blood, sleep Health Outcomes for Minority and Underserved Men

What are the best strategies to improve implementation of evidence-based practices (EBP) to enhance effective health risk communication strategies among racial and ethnic minority males and underserved men? Examples of several issues that need to be addressed are: • Need for better definition of the role of families/communities in EBP (as co-therapists). • Requires less system fragmentation • Need for improved measurement, ...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 :

Our improved ability to develop, implement and disseminate EBPs tailored specifically for men in health disparity populations may help us move beyond current obstacles in addressing health inequities and improve health outcomes.

Some current challenges:

• High blood pressure affects more than 40 percent of African Americans.

• The odds for stroke, the third leading cause of death in the United States, are especially high for African American men at 70%.

• African Americans are about 50% more likely to experience stroke than Caucasians.

• Sleep apnea is seen more frequent among men than among women, particularly among African-American and Hispanic men.

• Life expectancy for African American men is 4.7 years less than for white men (2010).

• Native American men have an average life expectancy of 71 years old compared to white men who have an average life expectancy of 76.5 year.

Feasibility and challenges of addressing this CQ or CC :

• Shifting demographics of race as well as ageing of the population in this country will have a major impact on the utilization, organization and delivery of health care.

• Country acknowledges significant economic burden of health inequities in the U.S. in the near future.

• Hospitals and health systems are working hard to align quality improvement goals with disparities solutions. Opportunity to leverage these efforts for the development and implementation of targeted health disparities initiatives is timely.

• HL has a number of large population-based studies (such as JHS, Strong Heart, Hispanic Community Health) that could be leveraged to specifically identify EBP for wider implementation and dissemination to underserved areas.

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

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14 net votes
32 up votes
18 down votes
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Goal 3: Advance Translational Research

Understanding Chronic Lung Disease Subtypes

What are the subtypes of chronic obstructive lung disease that share a common pathogenesis and can be a basis for precision medicine?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

Chronic Obstructive Pulmonary Disease (COPD) is a complex heterogeneous syndrome. The current approach of regarding this disease as a single entity has limited the ability to develop effective therapies and prevention. Understanding the major subtypes of COPD could lead to more biologically relevant disease classifications, improved prognostic information, and precision medicine treatment.

Feasibility and challenges of addressing this CQ or CC :

The optimal analytical approaches and data types to define complex disease subtypes have not been determined.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and COPDGene Executive Committee

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32 net votes
50 up votes
18 down votes
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Goal 3: Advance Translational Research

Regenerative Medicine 2.0 in Heart and Lung Research - Back to the Drawing Board

Stem cell therapies have been quite successful in hematologic disease but the outcomes of clinical studies using stem cells for cardiopulmonary disease have been rather modest. Explanations for this discrepancy such as the fact that our blood has a high rate of physiologic, endogenous turnover and regeneration whereas these processes occur at far lower rates in the heart and lung. Furthermore, hematopoietic stem cells ...more »

Submitted by (@jalees)

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

Details on the impact of addressing this CQ or CC :

Some barriers to successfully implementing cardiopulmonary regeneration include the complex heterogeneous nature of the heart and lung.

 

Hematopoietic stem cells can give rise to all hematopoietic cells but the heart and lung appear to contain numerous pools of distinct regenerative stem and progenitor cells, many of which only regenerate a limited cell type in the respective organ. The approach of injecting one stem cell type that worked so well for hematopoietic stem cells is unlikely to work in the heart and lung.

 

We therefore need new approaches which combine multiple regenerative cell types and pathways in order to successfully repair and regenerate heart and lung tissues. These cell types will likely also require specific matrix cues since there are numerous, heterogeneous microenvironments in the heart and lung.

 

If we rethink our current approaches to regenerating the heart and lung and we use combined approaches in which multiple cell types and microevironments are concomitantly regenerated (ideally by large scale collaborations between laboratories), we are much more likely to achieve success.

 

This will represent a departure from the often practiced "Hey, let us inject our favorite cell" approach that worked so well in hematologic disease but these novel, combined approaches targeting multiple endogenous and/or exogenous regenerative cells could fundamentally change our ability to treat heart and lung disease.

Name of idea submitter and other team members who worked on this idea : Jalees Rehman

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

Preserving and promoting expertise in integrative physiology

From my perspective, one of the key “critical challenges” facing the NHLBI in particular, and medical science in general, is to avoid being blinded by the promises of the reductionists in the “personalized, precision medicine” of the future. In order to understand the advances being made at the molecular level, we need to preserve and promote expertise in truly integrative physiology, what I like to call “PHYSIOMICS”. ...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 :

Unfortunately, human physiologists are being squeezed out of the medical industrial complex by the basic scientists on one end, and the epidemiologists on the other. Most departments of medicine now require on 80/20 commitment to have a significant research component of an academic career, and it is becoming increasingly difficult for those few of us physiologists remaining to compete with the pressures of both research funding and clinical mandates. I urge the leadership at NHLBI to preserve a strong focus on human physiology, and continue to support the small, but high resolution studies that are required to answer key research questions. I would submit that studying an individual patient’s unique physiology is as much “personalized” or “precision” medicine as it is to read their genome. Remember, despite billions of dollars of research support, there remains nothing better to predict the risk of diabetes, than a simple measure of waist size!

Name of idea submitter and other team members who worked on this idea : Benjamin Levine

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6 net votes
16 up votes
10 down votes
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Goal 3: Advance Translational Research

A Collaboration Market Place for Industry and Academia to advance Translational Medicine

There is a vast amount of data regarding specific gene and protein targets, especially in the post genomics era with many well validated targets, and even more "strong candidates". Drug companies have libraries of compounds that could be good inhibitors/enhancers for these new targets but lack an internal program, IP of the target, or a sufficiently large market to initiate risky and expensive drug screens, let alone ...more »

Submitted by (@ims000)

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

Details on the impact of addressing this CQ or CC :

An NHLBI sponsored and funded "Market Place" could be set up to partner drug companies seeking funds to perform earlier phase screens with academic investigators seeking funds to learn more about their protein target or advance a therapy. NHLBI could fund a successfully paired collaboration up to 100% of the cost, with a sliding scale of matched-costs from the industrial partner based on their market capitalization (e.g. big Pharma at 100%, Medium Pharma at 50%, and early-stage Pharma at 0%)

 

Well thought-out global contractual agreements for "non-disclosure" and "IP sharing", beneficial to both parties before and after initial 'pairing' of a collaboration, would significantly enhance the speed and feasibility of the studies.

 

More compounds could be tested for more targets, addressing rarer conditions, or common conditions where only a small proportion of the affected cases are impacted by mutations or deficiency of the target proteins.

 

Drug companies would be incentivized to examine more targets without necessarily needing a large market for a future drug.

 

Later stage studies – pre-clinical, Phase 1, and Phase 2 – could then be re-championed at the Market Place for additional NHLBI funding, either with new partners or the same partners to further advance successful compounds.

Feasibility and challenges of addressing this CQ or CC :

Contractual negotiations between Industry and Academia/Clinicians is a significant barrier to Translational Medicine and personalized medicine in particular.

 

Often ideas are not shared simply due to a lack of non-disclosure agreements in place. A Market-place to share ideas behind a well-structured “non-disclosure” firewall at the NHLBI website would facilitate the speed of discussion and stimulate collaboration.

 

Funding within industry can be limited by board and share-holder goals. There is typically little incentive to advance translational programs at early stages with no or limited medium or long-term financial benefits. Providing funding to facilitate and perform these research collaborations would incentivize Pharma to collaborate with academics who may hold IP or data on novel targets discovered with NHLBI funding.

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

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27 net votes
45 up votes
18 down votes
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Goal 3: Advance Translational Research

Addressing Unrecognized and Over Diagnosis of COPD

How can we create precision diagnostics for COPD in practice settings that will help inform the transition from screening to better diagnosis and treatment strategies and that will help identify patients or communities at highest risk for unrecognized or over diagnosed COPD.

Submitted by (@jsullivan)

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

Details on the impact of addressing this CQ or CC :

About 12 million individuals are estimated to have undiagnosed COPD and in most cases patients aren’t diagnosed until they have lost over half of their lung function leading to worse outcomes short and long term. Conversely there are challenges with over and mis diagnosed COPD that can result in over treatment and incorrect treatment. Fine tuning screening, diagnostic and management tools can result in earlier and proper identification of disease, earlier initiation of risk mitigation and/or treatment strategies and improved health outcomes as well as improved efficiencies in the healthcare system.

Name of idea submitter and other team members who worked on this idea : COPD Foundation, Nancy Leidy, COPDF MASAC

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11 net votes
12 up votes
1 down votes
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Goal 4: Develop Workforce and Resources

DEVELOPMENT AND SUPPORT FOR APHERESIS MEDICINE INVESTIGATORS

The apheresis medicine encompasses treatment of numerous diseases many of which are directly related to blood, lung and heart. However, there are very limited opportunities for training young investigators in basic and translational research related to Apheresis Medicine. There is a need to promote Apheresis Medicine as a viable field of research for junior and established investigators. The influx of well-trained junior ...more »

Submitted by (@zbigniew.m.szczepiorkowski)

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

Details on the impact of addressing this CQ or CC :

Therapeutic apheresis is the process of transiently removing whole blood from the body, separating it into various components (e.g., cells, plasma, proteins, antibodies, antigen-antibody complexes, lipids, etc.), removing those components that contribute to disease, and then returning the remaining blood with possible addition of a blood component to the body.

 

Hundreds of thousands of apheresis procedures are being performed every year in the US. Many of these procedures are life-savings while others are likely to be of limited benefit to patients and healthcare system at large. There is lack of good understanding pertaining to basic mechanisms of apheresis and optimal ways of applying apheresis to the improvement of underlying conditions as well as to the ability of apheresis to enhance other treatment modalities. This in turn is caused by significant shortage of well-educated and trained physician scientists willing to address basic science and translational-clinical questions related to applications of apheresis in clinical practice.

 

Currently there are no specific mechanisms for training such individuals. Utilization of and integration with existing educational/training programs, such as T32 grants, K23/K24/K25 grants, institutional K12 awards and CTSA educational programs would likely result in the cadre of junior investigators who can tackle questions related to basic mechanisms as well as clinical approaches to treating diseases using apheresis strategies.

Feasibility and challenges of addressing this CQ or CC :

Feasibility: Incorporation of apheresis medicine training into currently available resources is likely to be highly feasible. This training can be provided across many medical specialties including hematology, transfusion medicine, cardiology, pulmonology and others. Inclusion of basic scientists involved in research of blood disorders, lung and heart disorders, as well as immunology will expand the outreach. Identification of individuals interested in pursuing research in apheresis medicine might be accomplished on different levels of training starting with medical school, internship, residency and fellowship as well as early years of medical career in a variety of medical specialties.

 

Challenges: The primary challenge is related to perception. Apheresis has an undeserved reputation as an "old" science; one that in recent years has been overtaken at times by newer medical treatments. Yet it still is the only and often life-saving treatment for certain conditions. Apheresis remains the go-to procedure for treating many common and rare maladies alike, such as TTP, and new treatment indications are being added. Although many specialists like hematologists, neurologists, nephrologists see the evidence and benefits of therapeutic apheresis in their everyday work, the progress of Apheresis Medicine as a medical specialty has been generally slow. The other major challenge is lack of funding of basic research and translational research related to Apheresis Medicine.

Name of idea submitter and other team members who worked on this idea : Zbigniew M. Szczepiorkowski, Yanyun Wu on behalf of ASFA

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108 net votes
127 up votes
19 down votes
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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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12 net votes
20 up votes
8 down votes
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Goal 2: Reduce Human Disease

What is the optimal treatment goal for hypertension?

In adults without diastolic hypertension (DBP ≥ 90 mm Hg), what is the best way to determine at what systolic blood pressure should treatment be initiated?

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 :

The failure to resolve the debate about what is the appropriate goal for treatment of systolic hypertension could adversely effect the progress we have made in reducing the level of systolic blood pressure among the one third of adults with hypertension. At the heart of this debate is what is the optimal balance between lowering systolic blood pressure versus causing adverse consequences in those who are being treated for hypertension.

Feasibility and challenges of addressing this CQ or CC :

Because the existence of large clinical research networks with electronic medical records and use of generic drugs, all mean that a large pragmatic trial is definitely feasible.

Despite fifty years of clinical trial research and forty years of national guideline activity, important clinical questions remain under intense scientific debate. The importance of these questions is underlined by the scientific consensus that hypertension is the most important cardiovascular risk factor globally, in fact, more important than even tobacco use. Further hypertension research could be important because of the role of hypertension not only in CVD, but also in chronic kidney disease, stroke, and possibly in dementia and age related cognitive decline.

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

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13 net votes
28 up votes
15 down votes
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