Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Goal 2: Reduce Human Disease

Interaction between organ systems during ischemia and reperfusion

What is the mechanistic interaction of injured organ systems during total body ischemia and reperfusion?

Submitted by (@rebecca.lehotzky)

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 : AHA Staff & Volunteers

Voting

-3 net votes
1 up votes
4 down votes
Active

Goal 2: Reduce Human Disease

Combination Iron Chelator Trials in Thalassemia and other transfusion-dependent anemias

Three chelators are presently available in the US and much of the world: parenteral deferoxamine, and oral deferasirox, as well as oral deferiprone. Monotherapy is unsuccessful in a significant minority of patients, due to side effects or inadequate response at tolerable doses. Taking a page from enormously successful strategies for combination oral therapy in hypertension, led by NHLBI and others over the past four ...more »

Submitted by (@gcioffi)

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

Feasibility and challenges of addressing this CQ or CC :

NHLBI should lead the way for these trials, which will be of enormous benefit to reduce morbidity and mortality in thalassemia, a terribly common problem worldwide, as well as in the rare, transfusion-dependent congenital anemia.

Voting

39 net votes
54 up votes
15 down votes
Active

Goal 2: Reduce Human Disease

Systems Approaches to "Phenosimilar" Diseases

There are diverse diseases that share similar features. For example, many chronic airways diseases (chronic aspiration, ciliary dyskinesia, some COPD) "phenocopy" cystic fibrosis in terms of infectious agents, mucus clearance problems, progressive loss of lung function, etc. Use multiplatform "omics" approaches and Big Data bioinformatics to identify common nodes for therapeutic targeting. Other examples: emphysema and ...more »

Submitted by (@jhagood)

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

Details on the impact of addressing this CQ or CC :

may be able to target multiple diseases with new or repurposed therapies. Might narrow down the broad array of potential "high value" targets to study.

Voting

4 net votes
12 up votes
8 down votes
Active

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

Goal 2: Reduce Human Disease

Is there a Biomarker for the Pulmonary Fibrosis of HPS?

Hermansky-Pudlak Syndrome is characterized by a bleeding disorder as well as pulmonary fibrosis. Invasive procedures such as a lung biopsy are contraindicated due to bleeding and bronchoscopy is not without risk. Finding a biomarker would reduce the necessity for more invasive data collection while improving outcomes.

Submitted by (@dappell)

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

Voting

2 net votes
3 up votes
1 down votes
Active

Goal 2: Reduce Human Disease

Hosting International Studies on Rare Diseases

A programmatic initiative that would transform the NHLBI for rare diseases is to host some international studies.

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 :

The rest of the world is far ahead of the US in Registry science (e.g.. OrphaNet). To take a very rare disease (e.g.. Bechet’s pulmonary aneurysms, or hypocomplementemic urticarial vasculitis associated COPD) and establish an RFA to blend an international Registry with capability for hosting a clinical trial, and 3 years later an RFA to use the biorepository for proof of principal studies and a clinical trial would accelerate the international science agenda to a degree that might be unimaginable. Once established for 1 disease, the infrastructure should be kept intact for other diseases.

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

Goal 2: Reduce Human Disease

Disease Severity Biomarkers for Sickle Cell Disease

Can we identify biomarkers that can predict sickle cell disease severity?

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 :

Identifying reliable biomarkers that can predict severity of sickle cell disease could help doctors and patients make better decisions about a wide range of clinical decisions, including weighing the risks vs. benefits of bone marrow transplantation, chemotherapeutic manipulation of Hb F level, and gene therapy, all of which have potentially life-threatening complications.

Feasibility and challenges of addressing this CQ or CC :

Scientific advances make it feasible to identify biomarkers of disease severity. However, identifying biomarkers with good sensitivity and specificity is likely to be a challenge.

Name of idea submitter and other team members who worked on this idea : The Sickle Cell Association of New Jersey

Voting

7 net votes
7 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

New anti-thrombotic approaches with minimal adverse effect of bleeding

All current anti-thrombotic drugs have the adverse effect of excessive bleeding, which is associated with mortality and poor prognosis. Thus, there is a need to develop new generations of anti-thrombotics that have minimal adverse effect of bleeding.

Submitted by (@xdu000)

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 : Xiaoping Du

Voting

7 net votes
9 up votes
2 down votes
Active

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 »

Submitted by (@bldbuddy)

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

Pulseless Electrical Activity (PEA) - replacing VF/VT

As VF/VT rates continue to decrease in cardiac arrest to levels below 25%, the importance of understanding the pathways and epidemiology of PEA gains public health importance. Additionally, there is a need to determine the co-morbidities and/or pharmacologic agents that contribute to the causation of this rhythm.

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 :

Greater understanding of PEA would lead to better treatment (good CPR only treatment currently) and higher survival rate in CA

Feasibility and challenges of addressing this CQ or CC :

How will be treat the majority of cardiac arrest when it becomes PEA?

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

Voting

-9 net votes
7 up votes
16 down votes
Active

Goal 2: Reduce Human Disease

Towards Collaborative Funding of Clinical Trials

A way for clinical trial investigators to submit ONE application with ONE review and ONE funding decision, and the application would ask for funding from multiple funders (e.g. NHLBI and another IC, NHLBI and PCORI, NHLBI and AHA, NHLBI and CIHR, NHLBI and MRC).

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 :

It would be much easier for investigators from multiple sites/countries to secure funding for large-scale trials from multiple sponsors. They would only have to submit ONE application, respond to ONE review, and anticipate ONE funding decision.

Feasibility and challenges of addressing this CQ or CC :

Clinical trials have become increasingly difficult to afford, yet the need for them has never been greater. Many other sponsors (CIHR, PCORI, AHA, MRC, European Union) are eager to work with NHLBI to enable user-friendly multi-sponsor funding. Some similar type arrangements are already happening with other IC's (e.g. NINDS is working with CIHR and the UK MRC).

Large-scale clinical trials often require involvement of multiple sites, often located in > 1 country. Furthermore, the expense of trials often raises questions as to whether funders could collaborate, all contributing a certain amount. However, there is no simple user-friendly way for applicants to bring secure multiple sources of funding. Ideally, the division of funds would be agreed upon prior to application. In case of foreign funders, no monies would cross borders -- i.e. for NHLBI and UK MRC applications, the NHLBI would fund American sites while the UK MRC would fund UK sites, but all funding goes to ONE trial with ONE protocol and ONE data set.

 

One challenge would be politics. Who will do the review? NIH has traditionally acted as if it is the only agency capable to doing a valid review. Would NIH be willing to accept a review conducted by another sponsor? Would other sponsors be willing to accept a review fully run by NIH?

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

Voting

-1 net votes
8 up votes
9 down votes
Active