Strategic Goal: Goal 2: Reduce Human Disease

Fetal basis for Adult Disease

Maternal exposures during pregnancy have the potential to alter development and lead to lifelong susceptibility to disease. There is epidemiological evidence of this in the asthma field, where maternal smoking leads to increased asthma rates. However, the molecular mechanisms by which maternal exposures cause lung disease later in life are not known and the influence of in utero exposures on susceptibility to lung cancer, ...more »

Submitted by (@dc0000)

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

Details on the impact of addressing this CQ or CC :

Addressing the impact of maternal exposures on fetal lung disease would make a major impact on human health by giving regulatory agencies the data they need to make educated decisions with respect to issues such as nicotine regulation, air pollution, water pollution, and other sources of maternal exposures.

Feasibility and challenges of addressing this CQ or CC :

With the established animal and stem cell models of development, this research is immediately feasible.

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

Voting

10 net votes
17 up votes
7 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Risk-benefit of oral hypoglycemic medication in type 2 diabetes

Is an increase in macrovascular endpoints outweighed by the benefit in microvascular end points in new oral type 2 diabetes drugs?

 

It would go against the current regulatory paradigm in type 2 diabetes. Although drug companies do not like the current paradigm, they would prefer to go back to the pre-rosiglitazone state of affairs, in which new drugs had only to prove that they lowered blood glucose and HbA1c.

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Trials along this line would create a new and more rational paradigm to evaluate the cardiovascular safety of new oral hypoglycemic agents in type 2 diabetes in the context of their incremental benefit in preventing microvascular complications.

Feasibility and challenges of addressing this CQ or CC :

Some of the newer oral meds for treating type 2 diabetes, starting with rosiglitazone, have shown no benefit on clinical macrovascular end points, particularly heart failure. The FDA has responded to this by requiring new drugs to undergo large non-inferiority trials demonstrating that these drugs cause no more than a 30% increase in macrovascular endpoints as a precondition for approval. Yet there is no requirement that microvascular events (renal dysfunction and failure, neuropathy, retinopathy and visual loss) even be documented in these trials. So we are allowing new agents like alogliptin and sitogliptin to be marketed without any direct evidence that they do anything good for patients other than lowering glucose and HbA1c levels and with some evidence of adverse CV effects. While it is reasonable to assume that surrogates like lower glucose and HbA1c will translate to reduction in microvascular events, this assumption is based on old studies using different classes of drugs in a different disease population and environment. Even if HbA1c and glucose remain good qualitative surrogates, there is no way to quantitatively compare benefits versus risks of new hypoglycemic drugs compared to placebo or other drugs. Novel statistical methods to look at weighted composites of microvascular and macrovascular endpoints would enable the key question of net benefit to be addressed with a reasonable sample size.

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

Voting

-7 net votes
9 up votes
16 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Childhood Interstitial Lung Disease

What is the natural history of the best characterized ChILD disorders (surfactantrelated sequence variants, neuroendocrine cell hyperplasia of infancy (NEHI),pulmonary interstitial glycogenosis (PIG),idiopathic pulmonary hemosiderosis)?

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 :

We know little about the natural history of many of the child entities, and their relative rarity makes it difficult for any one center to answer the major questions they pose. The children has begun a patient registry that will begin to address the issue of natural history and disease tracking.

 

a. To improve the power of such a registry, we suggest that support be provided to find novel methods to link this data base to available electronic medical records of participating centers in order to assess physiologic and other clinical associations with specific diseases.

 

b. Support for a biomarker repository holding serum, frozen and fixed lung tissue, patient DNA, RNA, and proteomic and metabolomic materials, and bronchoalveolar lavage effluent and cell pellets, will allow for genome wide analysis as well as proteomic and metabolomic analysis.

Feasibility and challenges of addressing this CQ or CC :

This question is best addressed in the context of a multicenter data registry, ideally linked to a clinical sample.

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
Active

Strategic Goal: 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

Voting

2 net votes
33 up votes
31 down votes
Active

Strategic Goal: Goal 3: Advance Translational Research

Safety and effectiveness of new direct oral anticoagulants

What is the optimal use of new direct oral anticoagulants?

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Vitamin K antagonist, warfarin, has traditionally been the mainstay of anticoagulation therapy. It requires frequent monitoring to maintain safe and effective dose and is associated with many food and drug interactions. A new generation of direct oral anticoagulants has been developed to overcome such shortcomings.

Two main classes of new direct oral anticoagulants are available: factor Xa inhibitors and factor IIa (thrombin) inhibitors. Their mechanism of action involves direct inhibition of a single factor within the coagulation cascade to exert an anticoagulant effect. The industry is positioning them as monitoring-free universal warfarin replacement products. However, use of new direct oral anticoagulants introduces two major clinical issues: majority of new generation anticoagulants do not have developed dose-monitoring assay and do not have antidotes to rapidly restore blood coagulation properties in patients with trauma, emergent surgery, or anticoagulation overdose. Addressing these issues would positively impact cardiovascular, pulmonary, benign hematology, and orthopedic services worldwide.

While the idea of a universal, low-maintenance, “one dose fits all” anticoagulant is highly appealing to both patients and physicians, it may be feasible to consider more targeted approach, where each new anticoagulant would be assessed for most plausible effect in the specific patient population with consideration to genetic s, sex, race, age, thrombosis history, and obesity

Feasibility and challenges of addressing this CQ or CC :

Rapid advancement in the field of new generation direct oral anticoagulants and multiplicity of new drugs introduce opportunity to conduct comparative effectiveness research and assess how different characteristics of new products may be appropriate for different patients. Increased use of new direct oral anticoagulants requires expedited development of assays and antidotes for safe and efficient therapy of millions of Americans.

 

 

A challenge is that the majority of the clinical trials for new direct oral anticoagulants were conducted by the industry with the main goal of demonstrating superiority, or non-inferiority to warfarin. Secondary analyses of these trials’ data for efficacy in specific patient population may be difficult. Prospective clinical studies in this area may require large sample size and establishing collaboration between hematologists and other involved clinicians.

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

Voting

4 net votes
31 up votes
27 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Exercise in congenital heart disease and arrhythmia syndromes

What are the true risks of physical activity and competitive sports for children/young adults with congenital heart disease and arrhythmia syndromes?

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 the quality of life of patients with congenital heart disease or arrhythmia syndromes who are currently restricted from competitive sports.

Feasibility and challenges of addressing this CQ or CC :

While we previously restricted many of these patients, the pendulum seems to be swinging back in terms of our thinking about this. While some preliminary data has suggested safety, more data is needed.

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

Voting

4 net votes
15 up votes
11 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Functional pulmonary imaging with noninvasive imaging techniques

Critical Challenge

Submitted by (@str0001)

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 dynamics are altered with diffuse lung disease. Pulmonary function testing is a mainstay for evaluating patients with diffuse lung disease. However, ability to assess alterations of local lung mechanics and physiology may elucidate those patients with varying outcomes and mechanisms of disease. Such local analysis is possible with imaging such as MR and quantitative computed tomography (CT).

Feasibility and challenges of addressing this CQ or CC :

Dynamic magnetic resonance imaging (MR) techniques are available that are capable of evaluating the oxygen delivery and blood flow to regional areas of the lung and measurement of pressures in the heart and vasculature. Additionally, advanced dual-energy CT techniques enable assessment of blood volume within the lungs. Such techniques can be applied to pulmonary vascular and pulmonary parenchymal disease and combinations of the two. For example, an understanding of the cardiopulmonary interaction and phenotyping of pulmonary hypertension is needed. A need exists to determine if advanced CT technology and MR can identify patients with the emerging phenotypes of combined pulmonary hypertension, in which the degree of pulmonary hypertension is greater than expected from cardiac and pulmonary causes. MR can potentially serve as early predictors of these phenotypes, given MR’s ability to evaluate the parenchyma, the pulmonary vasculature, and heart, and in combination with other biomarkers determine appropriate therapy.

Name of idea submitter and other team members who worked on this idea : Society of Thoracic Radiology

Voting

3 net votes
6 up votes
3 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Pulmonary Complications of Sickle Cell Disease

What are the risk factors and components of clinical course associated with progression to restrictive lung disease, and what approaches to treatment can limit this progression?

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 :

RLD is a major risk factor for death in adults, but there is minimal knowledge of the sequelae of contributing factors. There is no longitudinal study to demonstrate the risk factors, determinants, biological. A cross sectional study of adults could determine prevalence of lung function abnormalities, obstructive and restrictive, using standardized testing and understand the factors associated with the presence of these abnormalities. This study could be associated with a clinical trial of treatment of RLD with outcomes of symptom reduction as well as improvement of the restriction.

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

Voting

1 net vote
2 up votes
1 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Prevention of rheumatic heart disease

Global health system outcomes studies are needed to identify impediments to successful primary and secondary prevention of rheumatic heart disease.

Other approaches, such as development of a vaccine for group A streptococcus and delaying disease progression once valve damage is present, could also be explored.

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

On a global basis, rheumatic fever remains the primary cause of valvular heart disease. Although the prevalence is much less in developed countries, pockets remain among groups with less access to healthcare.

Feasibility and challenges of addressing this CQ or CC :

Global health outcome studies could be performed over the next 5-10 years. The use of recently-developed point-of-care diagnostic tests could support these studies.

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

Voting

-10 net votes
7 up votes
17 down votes
Active

Strategic Goal: Goal 3: Advance Translational Research

Increasing Regenerative Medical Strategies in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a complex, progressive condition characterized by high blood pressure in the lungs and restriction of flow through the pulmonary arterial system. Current PAH therapies mainly act of the vasoconstrictive component of the disease; however there is a widely accepted view that another contributor to the disease is an abnormal overgrowth of cells that line the pulmonary arteries, which ...more »

Submitted by (@michaelg)

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

Details on the impact of addressing this CQ or CC :

In the past twenty years, 12 PAH targeted-therapies have been approved by the FDA. This increase in disease state awareness and in the treatment armamentarium have contributed to an increase in average survival from 2.8 years to an estimated 8-10 years. However, current treatments primarily address the vasoconstrictive component of the disease and do not address the now accepted theory of post-apoptotic overgrowth of hyperproliferative cells of the pulmonary vessels. A number of circulating stem and progenitor cells, derived from the bone marrow, have been identified that could have roles in repair of the pulmonary vascular system when interacting with the quickly, abnormally growing cells in the lung vessels. Work in this area has been named as a future research opportunity in the NHLBI-ORDR Strategic Plan for Lung Vascular Research (Erzurum S, et al. 2010).

Feasibility and challenges of addressing this CQ or CC :

Basic and translational research support is needed—including high-throughput approaches such as phage display and large-scale proteomic analysis—to better understand the relationship between circulating bone marrow-derived cells, lung-resident stem and progenitor cells, and endothelial cells of the pulmonary arterial system.

Name of idea submitter and other team members who worked on this idea : Pulmonary Hyeprtension Association, Michael Gray, Katie Kroner

Voting

71 net votes
81 up votes
10 down votes
Active

Strategic Goal: Goal 2: Reduce Human Disease

Rare Diseases

A study section should be seated for clinical trials on rare disease. Members of this study section should consist only of individuals who have previously performed phase I and/or phase II trials, developed IND or IDE applications, or who have extensive experience in informatic or biometric support for clinical trials. My opinion is that seating individuals on these sections who have a laboratory career in cellular or ...more »

Submitted by (@nhlbiforumadministrator)

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 : ATS Member

Voting

2 net votes
2 up votes
0 down votes
Active

Strategic Goal: Goal 3: Advance Translational Research

Establish COPD Biomarkers

Specific biomarkers to monitor COPD disease activity are needed.

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 :

Much is understood about the pathogenesis of COPD at the cellular and biochemical level. There is no established way these insights can be used to test or implement new medicines. An explicit and economical set of procedures need to be established that will facilitate the development of new medicines and guide their clinical use.

Feasibility and challenges of addressing this CQ or CC :

Many very small studies have identified biomarkers that relate to COPD activity in large groups of patients. There is no clear regulatory path for these insights to lead to tests that can be used with confidence in the development and implementation of novel treatments. Realistic regulatory pathways and criteria should be adopted to facilitate the development biomarkers of disease activity in COPD.

Name of idea submitter and other team members who worked on this idea : COPD Foundation, COPD Biomarkers Qualification Consortium

Voting

15 net votes
17 up votes
2 down votes
Active