Goal 3: Advance Translational Research

Leveraging big data for T4 translation research

What approaches can help leverage the emerging big data in health and health care for observational and interventional implementation research in heart, lung, blood, sleep diseases?

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 :

• Integration of big data analytics into T4 research study design and interventions development

• Innovative linkages across multiple health and non-health sector data

• Innovative methods to analyze big data linked across sectors

• Various communities are using big data analytics to understand population health data (e.g. electronic medical records s) and opportunities exist for consolidation of these efforts and standardization of methodologies

Feasibility and challenges of addressing this CQ or CC :

• NIH now has focus on big data in its formative stages

• Significant amount of NIH’s budget is/will be dedicated to big data research

• NHLBI can leverage NIH’s investment by foster research in D&I big data analytics and systems science

• Future investment in big data should yield opportunities and focus efforts

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

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Goal 3: Advance Translational Research

Develop biomarker panel to predict CVD risk in -omics era

There is a need to utilize the vast data generated in -omics research to develop biomarker panels for better prediction of cardiovascular disease (CVD) risks. •Cardiovascular diseases develop over decades and different panels of markers may be required for different stages •Lead molecules as potential biomarkers need to be selected by a panel of experts •Standard procedures about sample preparation, data acquisition, ...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 :

•Develop specific and sensitive markers for early prevention with more predictive power. Biomarkers that can detect specific perturbations in the system, such as metabolic status and vascular integrity prior to the occurrence of the diseases can be used for early preventive treatment of cardiovascular diseases.

 

•Identify vulnerable population who cannot be identified by the current LDL-HDL profiling

 

•Allow for more personalized treatment

Feasibility and challenges of addressing this CQ or CC :

•An increase in system biology studies using –omic approaches have provided huge data to mine through and find potential biomarkers, such as microRNA, DNA, lipids, proteins, and other metabolites, which can be used to assess changes proceeding cardiovascular diseases occurrence.

 

•The NIH-wide Big Data to Knowledge (BD2K) initiative launched in 2012 may have laid out some framework.

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

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Goal 2: Reduce Human Disease

Relevance of cardiovascular disease associated with autoimmunity research

NIH estimates up to 23.5 million Americans suffer from autoimmune disease (AD) and up to 24 million from heart diseases. As a result, NIH and AHA estimates the annual direct health care costs for AD to be in the range of $100 billion and $200 billion for heart and stroke diseases. Yet this area of research has been neglected and underfunded. The proposition is for NHLBI to partner with other NIH institutes dealing with ...more »

Submitted by (@mboutjdir)

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

Details on the impact of addressing this CQ or CC :

Reduce the impact of autoimmune diseases on the heart and vascular system.

Feasibility and challenges of addressing this CQ or CC :

Generate RFAs dedicated to the field of autoimmune associated cardiovascular diseases.

Name of idea submitter and other team members who worked on this idea : M. Boutjdir

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Goal 2: Reduce Human Disease

How can the study of rare diseases inform our understanding of common diseases?

How can the study of rare diseases inform our understanding of common 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 : Research Advocacy Committee, American Thoracic Society

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Goal 3: Advance Translational Research

Novel Mechanism for Clinical Trials of New Pro-Hemostatic Agents in Hemophilia

There are new exciting novel pro-hemostatic therapeutics in early phase clinical trials for hemophilia and hemophilia inhibitor patients. Yet, it is difficult to design randomized trials to compare these agents, or compare them with standard treatment, given the small sample size and competing studies for such patients. It is critical to develop novel approaches to compare new agents in rare populations. For example, ...more »

Submitted by (@ragni01)

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

Details on the impact of addressing this CQ or CC :

Should rare disease-specific strategies for clinical trials be developed, it would revolutionize the approach to study of not only rare disease populations, but all disease groups, no matter their size. If validated, rare disease-specific clinical trial strategies, would potentially reduce the cost, time, patient burden, and research effort to conduct clinical trials. If validated, consideration could be given to drug licensure earlier in the trial process, with a requirement for all such trials to initiate and continue ongoing data collection post-licensure for safety and efficacy.

Feasibility and challenges of addressing this CQ or CC :

Novel statistical methodologies are greatly needed to help with rare disease research. NHLBI might consider a grant mechanism RFA to encourage development of novel clinical trial strategies utilizing smaller sample size. The proof would be to develop the methodology as part of a feasibility study, and then, if feasible, adapt the novel approach to development and conduct of a clinical trial in a rare disease clinical tria,l to test the concept.

Name of idea submitter and other team members who worked on this idea : Margaret V. Ragni, MD, MPH (aspects discussed with Don Brambilla PhD.

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Goal 3: Advance Translational Research

T4 Translation Research Informing Early Stage Translational Research

There is a need to utilize insights gained from T4 translation research and implementation science to inform the design and execution of early-stage translational research and clinical trials.

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 :

• Assure that early stage translation research will be suitable for implementation in real world setting

• Aligns the research interventions from T1-T3 research to those appropriate to T4 research

• Potential to focus early stage research in key high burden areas

• Provides research community an understanding of the connections from early stage to late stage translation research which will potentially refine research strategies and directions at all levels

Feasibility and challenges of addressing this CQ or CC :

• Promote the importance of translation to population of heart, lung, blood, and sleep researcher to broader research community

• Potential for more T4 research contributions for guiding investment into translation research from T1-T3

• Provide avenues for T1-T3 investigators to translate their ideas into positive outcomes for population health

• Successful T4 research will stimulate feedback loop and identify opportunities for early translation research

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

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Goal 3: Advance Translational Research

In-Vitro Assays to Predict Clinical Response

How can NHLBI support studies that produce in-vitro assays to predict clinical response and ways to translate those results into patient therapies through novel clinical trials, including those for small patient populations and rare diseases?

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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Goal 1: Promote Human Health

Role of the lymphatic system in heart, lung, blood, sleep health and diseases

What is the role of lymphatic system in normal function of the heart? Do dysfunctional lymphatics contribute to heart failure? Do lymphatics have a role in recovery after MI? It has been reported that lymphatic vasculature transport HDL during reverse cholesterol transfer. Do lymphatics have a role in atherosclerosis? What is the contribution of lymphatic system to asthma or COPD? Does the lymphatic system contribute ...more »

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 :

Understanding how lymphatic system contributes to normal physiology of heart, lung, blood, sleep systems will help also lead to new approaches for treatment of heart, lung, blood, sleep diseases.

Feasibility and challenges of addressing this CQ or CC :

Basic understanding of the development and hemodynamics of the lymphatic system and reagents to study the lymphatic function are available.

Lymphatic vasculature is essential for fluid hemostasis in the body, collects and returns the protein- and lipid-rich interstitial fluid to blood circulation, and also involved in immune cell trafficking and inflammation. Given these important physiological roles, function of the lymphatic system is expected to contribute to normal physiology of organs and its dysfunction to major diseases. There is very little or no information how the lymphatic system contribute to health and diseases of the cardiovascular, pulmonary and blood systems, and there are many unanswered questions. Answers to these questions may lead to new approaches for treatment of major HLB diseases. Main challenge is to get heart, lung, blood, sleep investigators interested in studying the contribution of the lymphatic system to heart, lung, blood, sleep health and diseases.

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

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Goal 3: Advance Translational Research

Genome Profiling

There is a need to facilitate the integration of genomic and epigenomic profiling into drug discovery efforts by using genomic methods to sequence and analyze blood disease subtypes.

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

Details on the impact of addressing this CQ or CC :

Despite the important information that has been generated from sequencing studies in various blood disorders, for many hematologic disease subtypes, the limited scope of sequencing and the insufficient number of cases sequenced has prevented researchers from gaining truly useful insights. Whole-genome sequencing of large numbers of samples, with an emphasis on poorly studied and rare entities, is required to fully define the landscape of genetic changes underlying the development of blood diseases. Further, genetic and epigenetic alterations that drive hematologic diseases and the extent to which normal cells are distinct from malignant cells needs to be more broadly elucidated since many blood diseases, including hematopoietic cancers, disturb epigenetic regulators. The knowledge gained from understanding these processes and integrating genomic and epigenomic profiles could provide additional precision medicine opportunities and guide drug discovery efforts.

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

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Goal 3: Advance Translational Research

Genome Profiling

What structural changes need to be implemented in the health-care community in order to support the use of genomic information in clinical trials and drug development for hematologic diseases?

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 various blood disorders, including hematologic malignancies, there are both inherited and somatic genetic alterations that contribute to predisposition, transformation, disease progression, responsiveness to therapy, and treatment complications. The presence of such genetic alterations underscore the need for the identification of rare but traceable mutations as well as the integration of such genomic information into clinical trials. By implementing a few structural changes in the healthcare sector, a clinical trial infrastructure can be established that accounts for proper application of sequencing technology. Some examples include the creation of genome diagnostic networks that address accrual of sufficient patients, procurement of suitable tumor/non-tumor material for sequencing, as well as pharmacodynamic and correlative biology studies in hematologic diseases.

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

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Goal 3: Advance Translational Research

Genome Editing and Gene Therapy

There is a critical need for the establishment of strategies that will determine the efficacy, safety, and toxicity of genome editing techniques specifically in hematologic diseases.

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

Details on the impact of addressing this CQ or CC :

Inherited monogenic hematologic diseases such as hemophilia, beta-thalassemia and sickle cell disease are prime targets for future application of genome editing technology. However, studies are still needed to advance our understanding of the biology of genome editing as well as determine which other disorders are amenable to genome editing correction. Emphasis on preclinical research that focuses on determining the accuracy, safety and efficiency of this technology in order to help minimize off-target mutations and reduce toxicity, is essential for effective translation of this technology into the clinic. Once preclinical efficacy is established, support will be needed for clinical vector production, toxicity testing of the vectors/reagents used, and the performance of clinical trials. The gene correction strategies developed for inherited disorders will also be attractive for other hematologic diseases, and autoimmune disorders like lupus, rheumatoid arthritis, and type I diabetes). There is also a critical need for supporting preclinical validation studies, scale-up and GMP cell manufacturing, all of which could be shared infrastructures across multiple diseases in the NHLBI portfolio.

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

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Goal 2: Reduce Human Disease

Systems approaches to understand the pathogenesis of cardiovascular diseases, combined with in vivo validation

Critical Challenge

Submitted by (@yong.zhao)

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

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