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 1: Promote Human Health

Qigong and Tai Chi for Chronic Disease Prevention

Non-pharmacological interventions for pain and stress have gained tremendous momentum. Mind-Body Practice -- Qigong and Tai Chi -- are group based and inexpensive to implement. The evidence base suggests that these practices are safe and effective for a multitude of preventable chronic disorders.. THE QUESTION: Given safety and efficacy, should there be vigorous research on implementation of Qigong and Tai Chi and ...more »

Submitted by (@rogerjahnke)

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 can we do to assure that safe, effective, inexpensive non-parmacological approaches like Qigong and Tai Chi become widely diffused into communities, agencies, organizations, schools, health systems and businesses.

Feasibility and challenges of addressing this CQ or CC :

We have participated in a number of studies that have contributed to the evidence base for Mind-Body Practice as a safe and effective non-pharmacological programming.

 

The key -- group based. For the financing, group based is inexpensive. For the efficacy group based supports compliance.

Name of idea submitter and other team members who worked on this idea : Dr Roger Jahnke, http://IIQTC.org

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2 net votes
33 up votes
31 down votes
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Goal 2: Reduce Human Disease

Basic Research & Precision Medicine

How can NHLBI best encourage basic research areas that are critical to the development of precision medicine approaches for lung disease?

Submitted by (@skrenrich)

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
3 up votes
5 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 2: Reduce Human Disease

The role of Extracorporeal Photopheresis (ECP) in the prophylaxis and treatment of acute & chronic Graft Versus Host Disease

In Acute Graft Versus Host Disease (aGVHD), we would like to examine whether early and intensified delivery of ECP as part of standard prophylaxis will decrease overall corticosteroid exposure while preserving expected relapse rates in patients undergoing unrelated donor hematopoietic stem cell transplantation (HSCT). Chronic GVHD (cGVHD) is common after HSCT (30-50% recipients) and is a major contributor to late transplant-related ...more »

Submitted by (@js2745)

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

Details on the impact of addressing this CQ or CC :

Patients who develop aGVHD undergo toxic therapy with high-dose corticosteroids, often for long durations, resulting in high morbidity and treatment related mortality. Alternatively, T cell depletion of the donor graft to reduce GVHD is associated with high rates of infection and relapse of the disease that led to the HSCT. Targeting other pathways of GVHD pathogenesis may preserve the beneficial immune reconstitution and graft-versus-tumor (GVT) effects, while ameliorating the severity of GVHD. One such pathway involves regulatory T cells (T regs), which inhibit T cell alloreactivity, and are correlated with the incidence and severity of GVHD without loss of GVT. To date, there is no consensus on a standard second-line therapy for aGVHD, and current approaches focus mainly on intensification of immunosuppression. Addressing this compelling question will help to decrease overall corticosteroid exposure while preserving the expected relapse rates in patients undergoing unrelated donor HSCT.

 

Appropriate initial therapy for cGVHD involves high doses & prolonged use (yrs) of corticosteroids, while patients still develop irreversible sclerotic manifestations of disease. Early intervention prior to disease onset may help prevent cGVHD development or lessen its severity, requiring less corticosteroid exposure. Addressing the compelling question for cGVHD will help decrease exposure to drugs with associated morbidity, while preserving expected relapse rates in these patients.

Feasibility and challenges of addressing this CQ or CC :

Feasibility:

 

* GVHD has relatively high incidence after HSCT and at the same time there is a lack of consensus on standard second line therapy for the disease. Thus, there will be increased interest in developing and participation in those studies.

 

** ECP is generally well tolerated and complications are infrequent.

 

*** There is a great potential for multi-discipline collaboration approach in this patients’ population.

 

*** There is an opportunity to engage industry partners in the design and support for these studies.

 

**** There are numerous scientific opportunities for meritorious science as there have been limited systematic studies of ECP mechanisms of as well as standardization of apheresis protocols based on GVHD disease state.

 

 

 

Challenges:

 

* Limited number of institutions providing ECP treatment.

 

** Cost of the procedures (although Centers for Medicare and Medicaid Services now covers ECP for cGVHD).

 

*** There is a very limited number of animal models available for apheresis research in general, and studies of the mechanism(s) of action of photopheresis have been very limited as well as difficult and expensive to perform. However understanding pathological mechanisms and its relationship to response to apheresis is critical for optimization and advancement of patient care.

 

****Lack of infra-structure for apheresis research.

Name of idea submitter and other team members who worked on this idea : Joseph Schwartz on behalf of ASFA

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103 net votes
126 up votes
23 down votes
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Goal 2: Reduce Human Disease

Bringing Personalized Biochemistry and Biophysics to Bear on Problems of Personalized Heart, Lung and Blood Medicine

Precision medicine will provide unprecedented opportunities to tailor health care based on knowledge of personal patterns of genetic variations. These variations usually impact protein or RNA sequences, resulting in altered properties. These alterations can result in increased susceptibility to a particular disease or intolerance to common therapeutics. To take full advantage of knowing a patient’s set of gene variations, ...more »

Submitted by (@chuck.sanders)

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

Details on the impact of addressing this CQ or CC :

As detailed in the attached review (Kroncke et al. Biochemistry 2015, 54, 2551−2559) the successful practice of personalized medicine will in many cases require a molecular-level understanding of the nature of the defects that are caused by disease-predisposing genetic variations. As widespread personal genome sequencing becomes routine, numerous genetic variations (many millions) of uncertain significance will be discovered. Using both experimental and computational tools associated with the fields of biochemistry, biophysics, and structural biology it is in many cases possible to ascertain whether a newly-discovered gene variation adversely impacts a critical protein or RNA function and, if so, how. Among various clinical applications this information can be used (i) to project whether a patient not currently showing symptoms for a particular disease is likely to present with that disease in the future (sometimes enabling prophylactic therapy), (ii) to help establish the molecular etiology of a disease currently afflicting the patient, and (iii) to guide the therapeutic strategy pursued for that patient.

Feasibility and challenges of addressing this CQ or CC :

My lab is already participating in a project (RO1 HL122010) with two other labs (those of Drs. Jens Meiler--Vanderbilt and Alfred George--Northwestern) to develop personalized biochemical and biophysical approaches for application to genetic variations impacting the KCNQ1 gene, potentially predisposing patients to long QT syndrome, a cardiac arrhythmia. However, our project deals with one gene and one disorder only. There clearly is a need for improved and expanded communication and collaboration between those practicing personalized/precision medicine and those who are well-equipped to provide medically actionable molecular insight using the approaches of personalized biochemistry, biophysics, and structural biology.

Name of idea submitter and other team members who worked on this idea : Charles R. Sanders, Prof. of Biochemistry, Vanderbilt University (With Drs. Alfred George--Northwestern University and Jens Meiler--Vanderbilt University)

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

Precision medicine in non-malignant lung diseases

NIH has a major initiative in Precision Medicine, including whole genome sequencing. In contrast to cancer, mutations with large clinical effects are expected to be uncommon in most non-malignant chronic diseases, such as asthma and COPD. Other data types such as gene expression, biomarkers, and micro RNAs must be combined with clinical and imaging phenotyping to advance Precision medicine in non-malignant lung diseases. ...more »

Submitted by (@craighersh)

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

Details on the impact of addressing this CQ or CC :

The goal is to combine clinical and molecular data to identify subtypes of patients within the major chronic respiratory diseases. Understanding molecular pathways will first lead to more appropriate drug repositioning and eventually novel drug development.

Feasibility and challenges of addressing this CQ or CC :

NHLBI has many cohorts of subjects with chronic lung diseases with longitudinal clinical characterization, many with banked biospecimens. It is quite feasible to perform genomic, epigenetic and biomarker assays on these specimens. Based on these results, hypothesis-based targeted profiling can be done in prospective studies.

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12 net votes
15 up votes
3 down votes
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Goal 2: Reduce Human Disease

Balancing Risks and Benefits: How Do Clinical Guidelines in Cardiovascular Medicine Promote the Health of an Individual?

Much of the hopes for precision medicine (as outlined Dr. Dr. Collins) are based on deriving large amounts of genomic, proteomic, epigenomic and metabolomic data on large cohorts of patients. It will take decades to build these cohorts and even more time to analyze them and derive specific conclusions on how these will help individualize treatments. However, there is a pressing need for how to individualize contemporary ...more »

Submitted by (@jalees)

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

Details on the impact of addressing this CQ or CC :

Decisions on whether or not to place a patient with atrial fibrillation on chronic anticoagulation or on statin therapy are often based on guidelines and cardiovascular risk calculators.

 

Patients with a higher risk of stroke are more likely to receive anticoagulation and patients with a higher risk of a myocardial infarction are more likely to receive statin therapy.

 

However, these cardiovascular risk calculators do not really take into account the potential side effects and impact on the lifestyle of the patients.

 

Physicians will stop anticoagulation in a patient with atrial fibrillation if the patient has suffered a life-threatening bleed but there are no specific evidence-based guidelines as to how one should proceed if the bleeding is minor.

 

it is easy to compute the cardiovascular risk and overall mortality benefit of placing a patient on statins but how does one factor in the impact that statins have on the quality of life of an individual?

 

Developing novel evidence-based approaches to individualize therapies that factor in cardiovascular benefits as well as potential side effects and diminished quality of life could have a major impact on appropriately using treatments and reduce the arbitrariness of some medical decisions.

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

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

Stem Cell Immunology

We now can create critical cell types like cardiomyocytes etc. from stem cells. Additionally, we are learning the rules of using these cells to rebuild tissues. A major gap in our knowledge relates to the immunobiology of these cells. Lessons from transplantation medicine are only partially applicable, because solid organs are more complex and likely more immunogenic than defined cell populations. How does the immune ...more »

Submitted by (@murry0)

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

Details on the impact of addressing this CQ or CC :

We now can generate large quantities of critical cell types whose deficiencies underlie many chronic diseases like heart failure. This breakthrough brings us to the next-level impediment: the immune system. While induced pluripotent stem cells have the potential to obviate rejection, in practical terms this is cost-prohibitive: It will cost huge amounts of money to produce and qualify a single patient's cell dose. Moreover, human cardiomyocytes are potent when given to infarcted hearts in the acute or sub-acute phase of infarction, but they have no benefit with chronic heart failure. The 6 months required to produce iPSC-cardiomyocytes precludes their autologous use for myocardial infarction.

 

We need an off the shelf cell therapy product for myocardial infarction that can be mass produced and qualified for large numbers of patients. This means an allogeneic product is necessary. Identifying the immune response to cardiomyocytes or other cell products will teach us how to precisely immunosuppress the patient, thereby minimizing complications, or alternatively, how to engineer the cells so as to avoid immunogenicity in the first place.

 

Lessons from the study of cardiomyocyte transplantation could extend to dopamine neurons, pancreatic beta-cells, retinal cells, myelinating cells and many other areas that cause common chronic disease.

Feasibility and challenges of addressing this CQ or CC :

We know a great deal of transplant immunology from hematopoietic stem cell transplantation (graft versus host) and from solid organ transplantation (host versus graft). There are good mouse and large animal (including non-human primate) models of stem cell differentiation and organ transplantation. This offers low hanging fruit where, in perhaps 5 years, we could discern the critical similarities and differences between transplanting stem cell derivatives and organ or marrow transplantation. These studies will inform clinical trials of allogeneic human stem cell derivatives that will be underway by then.

 

Success in this area will require bringing together researchers interested in stem cell biology and transplant immunology. A properly resourced RFA from NIH could be just the thing needed to promote this interaction.

Name of idea submitter and other team members who worked on this idea : Charles Murry, MD, PhD

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23 net votes
45 up votes
22 down votes
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Goal 3: Advance Translational Research

Harnessing the ongoing ‘natural experiments’ of quality improvement

How do we harness the ongoing “natural experiments” of quality improvement (QI) activities in various healthcare systems to facilitate hypothesis-driven research, improve scientific validity to address questions in clinical trials, and implement and disseminate research results? • Current restrictions in human subjects research regulations • Diversity in approaches and methodology rigor to QI initiatives across different ...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 :

• Publication of QI initiatives in peer-review journals

• Wider dissemination and adoption of best practices

• Establishment of methodologically rigorous QI programs with viable career pathways

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

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-2 net votes
11 up votes
13 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 2: Reduce Human Disease

DEVELOPMENT OF A PERSONALIZED APPROACH TO SLEEP AND CIRCADIAN DISORDERS

There is developing evidence of major individual differences in pathways to different common sleep disorders such as obstructive sleep apnea. Moreover, there is evidence of different clinical presentations of disease and different outcomes. For example, some subjects with obstructive sleep apnea who get excessive sleepiness while others do not. The latter are still at risk for other consequences of the disorder such ...more »

Submitted by (@jnoel0)

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 strong rationale for application of a personalized approach to sleep disorders. This requires approaching this question using multiple domains as in other areas of medicine—clinical features, physiological factors, application of the –omic approaches, genetics. The impact of this will be several:

 

a. A new way to classify sleep disorders.

b. Identification of subgroups of patients with apparently the same disorder who will have different outcomes of therapy.

c. Identification of subgroups of patients who will have different approaches to diagnosis.

d. Identification of subgroups of patients with apparently the same disorder who will have different therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

These sleep and circadian disorders are extremely common. There is a risk infrastructure for this type of research based on the large number of accredited sleep centers in the United States that could be used for subject recruitment and who can adopt similar techniques. There is also a rich set of data obtained from sleep studies that could be used to identify new patterns that reflect different subgroups of subjects. These studies need to be based on clinical populations of patients who present with the different disorders rather than on population-based cohorts.

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

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167 net votes
220 up votes
53 down votes
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