Goal 3: Advance Translational Research

Embedding Clinical Trials in Learning Health Systems

What are the best methods for using genotype information and other EMR data to randomize heart, lung, blood, sleep patients to different treatment strategies? One big challenge is how to consent patients for this sort of trial. Must patients be consented separately for every such trial or could there be blanket consent for participating in the learning health care model? This would also require a paradigm shift in how ...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 :

If successful this approach should enable the conduct of cheap pragmatic trials that are fueled by data from clinical care. The integration into clinical care helps assure efficiency and generalizability of results.

Feasibility and challenges of addressing this CQ or CC :

The advent of electronic medical records and the explosion of big data technology has made it possible to gain access to and analyze data in a manner that would have been unthinkable 10 years ago. This is already going on in other fields.

Health care systems are increasingly using "big data" approaches to track outcomes in the patients treated with different strategies and drugs, and apply the knowledge gained from outcomes in previous patients to inform decision making in subsequent patients ("learning"). This approach could be used to personalize treatment. A recent example from cancer is to genotype lung tumors, and tailor the treatment of a new patients to drugs producing good results in patients with similar tumor genotypes. When two or more treatments produce similar results, one could randomize. Cardiovascular disease presents a challenge in using genotyping information to personalize treatment, because the manifestations are the results of complex genetic and environmental risk factors.

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

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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

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Goal 1: Promote Human Health

Transforming Transplantation with Reprogramming Immune System Cells (RISC)

Can we "reprogram" the immune system to improve outcomes of heart, lung, and hematopoietic cell transplants? While NIAID is a major funder of immunology research, we are a major contributor to stem cell research. Our resources could be combined, where NIAID would support this approach for autoimmune diseases, and we would support work in tolerance for transplants. If the NCI also wants to collaborate on co-stimulatory ...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 :

This innovative and transformative proposal could improve tolerance to many different types of transplants.

Feasibility and challenges of addressing this CQ or CC :

In 2002, Hochedlinger and Jaenisch (Nature 415:1035-1038) created a mouse by nuclear transplantation from a mature B-cell. This was proof of principle that the immune system can be reprogrammed entirely. Since then there has been little work in this area, but Reprogramming Immune System Cells (RISC) is risky but promising.

A second approach involves mechanisms that cancer cells use to evade immune detection. While most cancer research works to restore immune competence for therapy, the basic biology of evading immune detection could be exploited to improve tolerance. These approaches could be tested in an animal model in 5 years.

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

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27 up votes
12 down votes
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Goal 3: Advance Translational Research

Advancing the science of translating evidence into practice

What are the best ways for the NHLBI to advance the evolving science of translating robust evidence into clinical practice domestically and globally? How to personalize broad research evidence for individual patients? How to predict and evaluate the impact of evidence-based interventions? How to identify implementation methods available in industry and elsewhere that work best and are most translatable in healthcare? ...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 :

• Reduce mortality and morbidity

• Improved quality of life

• Higher proportion of people receiving evidence-based care and at goal for that care

• Reduced disparities in health and healthcare

Feasibility and challenges of addressing this CQ or CC :

Challenges:

• Lack of research methodology in this area – may need new scientific approaches

 

• Lack of current capacities and capabilities in this area

 

• Current silos that separate research enterprise from industry, as well as NHLBI from other ICs

 

• Divisions between performance of clinical trials and implementation research

 

• Lack of clarity which federal agencies and NIH Institutes are ‘in charge’ of implementation and/or prioritize this as part of their mission and budget

 

• Lack of wide sharing of best practices of other implementation models

 

• Improving the science in this area needs to include methods and metrics development

 

• The accumulated knowledge of clinical trialists and implementation researchers is often not shared

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

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27 up votes
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Goal 3: Advance Translational Research

Clinical Trial Methodology

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan:

 

Are the current methodologies for clinical trials still the best practices for conducting efficient clinical trials?

Submitted by (@wheeze)

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 : Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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Goal 3: Advance Translational Research

Behavioral and Clinical Researcher Interactions

A critical challenge is the need to bring together basic behavioral scientists interested in understanding human behavior at a fundamental level, including how and why people become motivated and capable of undertaking behavioral changes, with clinical researchers interested in developing and testing new strategies for tackling resistant behavioral problems such as obesity and non-adherence.

Submitted by (@nhlbiforumadministrator1)

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

Feasibility and challenges of addressing this CQ or CC :

Obesity and non-adherence are two of the most important yet challenging behavioral problems contributing to cardiovascular morbidity and mortality. One way to address this challenge is to fund a network of “behavior change labs,” each of which bring together teams of basic behavioral scientists who are investigating the bases of behavior and behavior change with clinical researchers interested in designing, optimizing and testing novel ideas for tackling the difficult behavior problems of obesity and non-adherence to cardiac medications.

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

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Goal 2: Reduce Human Disease

Clinical Research for HIV/AIDS and HLB Health and Diseases

What HIV/AIDS-related clinical research can NHLBI support in the next 5-10 years on the prevention, diagnosis, and treatment of HIV-related heart, lung, and/or blood (HLB) diseases in adults and children to improve heart, lung, and blood health outcomes in HIV infections?

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 :

Remarkable progress in anti-retroviral therapy (ART) has increased survival in the HIV population and significantly reduced mother-to-child transmission of HIV both in resource-rich and resource-limited settings. However, this enhanced longevity is now associated with an increasing burden of chronic diseases, such as coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), and chronic anemia. In patients with HIV, there may be a complex interplay between the processes of inflammation, traditional risk factors, and the adverse effects of ART. Additionally, the long-term effects of in utero exposure to HIV and antiretroviral drugs in HIV-exposed but uninfected children on HLB diseases is unknown.

Furthermore, HIV control or possibly even HIV cure could result from developing novel cell therapies, especially hematopoietic stem cell (HSC) transplants, and might also result from early use of antiretroviral therapy in acutely HIV-infected individuals. Finally, other unique NHLBI research activities and resources could be leveraged for HIV/AIDS-related research.

Feasibility and challenges of addressing this CQ or CC :

• Collaborations between HIV and HLB investigators that have been facilitated by the NHLBI investments, including three RFAs.

 

• The Berlin patient has provided the proof of concept that HIV infection can be eradicated, that is, sterilizing cure can be achieved, through HSC transplantation in combination with other therapies;

 

• Recent studies have shown that early identification of HIV infection and treatment of infected individuals with anti-retroviral therapy as soon as possible can significantly limit the size of the HIV reservoirs even if such early treatment may not be able to completely prevent the establishment of HIV reservoirs; routine blood donor screening for both anti-HIV antibodies and HIV RNA among blood donors offers unique opportunities to identify acute HIV infections.

 

• For other NHLBI research activities and resources that could be leveraged: data and specimens are available in the NHLBI repositories as well as repositories of NHLBI investigators.

 

 

For HLB comorbidities of HIV infection, the challenges include:

 

• Closer collaboration and leverage of resources available

 

For HIV cure, the challenges include:

 

• Generation of HIV-resistant HSCs in adequate quantity for transplantation;

 

• Efficiency of homing and expansion of HIV-resistant HSC transplants, replacing HIV-infected cells, and immune reconstitution by HSC transplants

 

• Safety of HSC transplantation with needed GVHD to eliminate HIV-infected resting T cells

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

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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22 up votes
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Goal 3: Advance Translational Research

Integrated Clinical Guideline on Comorbidities in Primary Care

The development of systematic evidence reviews (SER) that provide the evidence that partner organizations can use to develop an integrated clinical practice guideline for use by primary care providers for the treatment of patients with single and multiple conditions for the primary and secondary prevention of heart, lung, blood, and sleep (heart, lung, blood, sleep) diseases.

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 :

• Despite the success of single condition/disease guidelines, patients often have multiple conditions/risk factors that interact in various ways and can accelerate the development of atherosclerosis and chronic lung diseases. Effective management therefore requires a more integrated approach to assessment and treatment that spans all of relevant risk factors and conditions.

• The development of an integrated guideline has been recommended by participants in several NHLBI forums, including the NHLBI Strategic Planning process, the NHLBI Conference to Create a Cardiovascular Knowledge Network, and the Cardiovascular Disease Thought Leaders Meeting.

Feasibility and challenges of addressing this CQ or CC :

Feasibility: • NHLBI currently participates with other Institutes in funding research on comorbidities, Behavioral Interventions to Address Multiple Chronic Health Conditions in Primary Care (R01, PA-12-024).

• An increasing number of scholarly articles are addressing the magnitude and cost of the problem and calling for guidelines that address this reality.

 

Challenges: .

 

• Few studies have focused on the management of patients with multiple chronic conditions.

 

• Clinical research often excludes persons with multiple chronic conditions.

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

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Goal 2: Reduce Human Disease

US-based Clinical Development of Innovative Medical Devices

Though innovative medical devices are often conceived of and developed in the US, US consumers are frequently the last to benefit. Innovators frequently go to market first in Europe and are now moving toward emerging countries, delaying the medical benefits available to the US population. Can the NHLBI and FDA’s CDRH, working together as sister agencies, develop strategies such as funding opportunities or collaborative ...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 :

Addressing this CC may empower the development of new regulatory paradigms within CDRH, enable the streamlined development of several NHLBI medical devices in the US, lead to a minimized delay in US availability for truly innovative technologies, and grow the pool of US clinicians experienced in working with device developers at the earliest stages of human/device interaction.

Feasibility and challenges of addressing this CQ or CC :

In the past 18 months

• NHLBI and CDRH have executed a structured working relationship, within the NIH Centers for Accelerated Innovations, where CDRH provides high-level feedback to early stage NHLBI medical device developers.

• CDRH has developed two new programs –one to enable US conduct of early feasibility studies/first-in-human (EFS/FIH) studies and a second to provide expanded access to senior agency reviewers for innovators developing high risk technologies.

Additionally, CDRH is focused on exploring and evaluating additional pilot programs to expand first-in-human trials within the US. NHLBI’s portfolio of awardees includes a number of medical device development projects that could qualify for the EFS/FIH program. Development of new collaboration or funding opportunities focused on this segment of device developers could attract additional innovators to the NHLBI family and encourage the US-based clinical development of their innovative technologies. The relationship that has been built between NHLBI and CDRH, in conjunction with CDRH’s more open approach to working with innovators, makes this the perfect time to expand NHLBI/CDRH innovator support beyond the NCAI program and into the overall NHLBI portfolio.

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

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19 up votes
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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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3 net votes
6 up votes
3 down votes
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Goal 2: Reduce Human Disease

Lung Transplantation

Although the majority of lung recipients experience significant health improvement, they also frequently face serious symptom distress, impaired physical functioning and poor quality of life due to post-transplant morbidity, such as chronic rejection, infection and multiple side-effects of immunosuppression. a) Conduct clinical trials of interventions designed to maximize clinicians' support of patients' self-management ...more »

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges of addressing this CQ or CC :

a) Conduct clinical trials of interventions designed to maximize clinicians' support of patients' self-management behaviors so that patients and clinicians working together can achieve optimal control of disease, reduce symptom distress and complications, and promote quality of life.

 

b) Evaluate the impact of integrating palliative care and transplant care for symptom management, goal setting and advanced care planning along the entire lung transplant illness trajectory (pre, post and end of life).

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

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