Strategic Goal: Goal 2: Reduce Human Disease

Metrics to Predict Success of Clinical Trials

What are the metrics that can predict success of clinical trials?

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 :

The ability to identify factors, both ahead of time, and during the trial, that will predict the success of the trial would permit considerable efficiencies for NHLBI. We should be able to select a group of trials that will be able to recruit on time and within budget. For others where there may be less chance of success, we may want to invest time and resources in mentoring the investigators (e.g., in the case of new investigators), or in helping to redesign the trial. This latter function could be especially helpful during the pre-application process.

Feasibility and challenges of addressing this CQ or CC :

NHLBI has developed a critical mass of expertise in portfolio analysis, and is working on developing the IT tools to match. This area was identified as a high priority by the internal IMPACT Task Forces at their recent retreat, so there is also widespread interest in this approach as well.

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

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Strategic Goal: Goal 2: Reduce Human Disease

Utilizing Competition to Enhance NHLBI’s Clinical Trial Enterprise

During this period of diminishing Federal resources and funding, what novel methods can be employed to effectively conduct clinical trials that address existing and emerging medical and public health issues?

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 :

Addressing thecritical challenge would improve clinical trial design, clinical trial efficacy and ultimately completion and reporting of trial results. This approach would most likely save money.

Feasibility and challenges of addressing this CQ or CC :

The Other Transaction Authority already exists within the PHS and NIH and this method has been tested at NCI.

Competition is an important element of successful achievement in everything from sports rivalries to scientific innovation. Examples of this can be cited for the Larry Bird and Magic Johnson hoops competition, Muhammad Ali versus Joe Frazier boxing duels, and the contest between the Human Genome Project and Celera for completion of the mapping of the human genome. The US Defense Advanced Research Project Agency (DARPA http://www.darpa.mil) has used the concept of competition to advance the development of never before imagined scientific and technological innovations including development of the internet, the SIRI voice recognition system, UNIX and the cloud, and the global positioning system, among many products and innovations. Under this paradigm great advances are initiated through a public challenge which brings competitors together to achieve a goal set by the government. This is accomplished through the use of the Other Transaction Authority (OTA), which has been extended to the NIH. Subsequent management of the challenge involves the setting of milestones and utilization of “go/no go” decision making. The NCI has used a “DARPA-like” approach to instill competition for the design and conduct of clinical trials and as a result has substantially improved the performance of its clinical trials networks / cooperative groups.

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

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6 up votes
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Strategic Goal: Goal 3: Advance Translational Research

Novel Technologies & Clinical Therapeutics

How can NHLBI harness the power of novel technologies involving nucleic acid delivery and gene editing for clinical therapeutics?

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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Strategic Goal: Goal 3: Advance Translational Research

Improving the conduct of cardiovascular clinical trial

There are increasing demands on clinicians for clinical productivity and increasing both clinical and research regulatory requirement. A paralle trend is an increase in clinical trials being conducting outside of US, which is a significant concern in terms of US participation and data applicability to US patients, and the quality of trials data from other regions. These trends have multiple roots spanning from patients ...more »

Submitted by (@javed.butler)

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

Details on the impact of addressing this CQ or CC :

Timely conduct of US relevant data to translate basic science discoveries into either clinical practice or knowing that something is not useful or harmful.

Feasibility and challenges of addressing this CQ or CC :

This will be challenging because it will need public education and advocacy as well as institutional leadership developing incentives and making clinical trials a priority.

Name of idea submitter and other team members who worked on this idea : Javed Butler, MD MPH MBA

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3 up votes
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Strategic Goal: Goal 3: Advance Translational Research

ASCVD Risk and Treatment Options

There is little evidence about the best ways in which to effectively communicate atherosclerotic cardiovascular disease (ASCVD) risk to patients so that they clearly understand the potential benefits and harms of treatments in order to make informed decisions about their care. A shift toward shared decision-making and tailored treatment makes it imperative that effective risk communication strategies be developed and ...more »

Submitted by (@nhlbiforumadministrator)

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

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-2 net votes
6 up votes
8 down votes
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Strategic Goal: 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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11 net votes
22 up votes
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Strategic Goal: Goal 3: Advance Translational Research

Using Single Patients for Clinical Trials

To foster the IOM recommendation that every healthcare encounter contribute to a learning healthcare system, would clinical practice structured as N-of-1 trials and documented via EHR/EMR provide strong practice-based evidence?

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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-20 net votes
9 up votes
29 down votes
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Strategic Goal: Goal 2: Reduce Human Disease

Comparison of CAC-based Strategy versus AHA/ACC Guidelines

There is a need for a randomized primary prevention trial comparing the effectiveness of cholesterol treatment strategies based on a high CAC score versus the AHA/ACC 10-year cardiovascular disease risk tool. Include cost-effectiveness as well as clinical effectiveness as endpoints.

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 :

Improve targeting of statins to high-risk patients without prior CV disease.

Feasibility and challenges of addressing this CQ or CC :

New guidelines issued last year. Statin and recently ezetimibe are proven to be safe and efficacious.

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

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-8 net votes
4 up votes
12 down votes
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Strategic Goal: Goal 2: Reduce Human Disease

Cardiometabolic Disease Risks Associated with Sleep Deficiency

How does insufficient sleep duration, irregular timed sleep schedules, and poor sleep quality contribute to the pathophysiology of lung, heart and blood 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 :

Sleep deficiency and untreated sleep disorders threaten the health of 20-30 percent of US adults through an increased risk of stroke, hypertension, diabetes, inflammatory disease, and all-cause mortality. Developing the scientific evidence-base of validated interventions will enhance the management of cardiometabolic and pulmonary risks to health, present new opportunities for secondary prevention, and reduce associated burden on health care systems.

Feasibility and challenges of addressing this CQ or CC :

Improving sleep health through informed public recognition of decision-relevant science, and relatively low cost therapies for management of sleep disorders are available for immediate assessment of impact in appropriate clinical trials to demonstrate efficacy and effectiveness.

Discovery research advances implicate an array of cellular sleep and circadian mechanisms in pathophysiological pathways leading to cardiometabolic and pulmonary disease.

 

Irregular and disturbed sleep impairs cellular biological rhythm in all tissues and organs leading to oxidative stress, unfolded protein responses, and impaired cell function. The pathophysiological findings juxtaposed with epidemiological evidence of disease risk indicate that sleep deficiency contributes to an erosion of health across the lifespan over and above the effects of aging.

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

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94 net votes
122 up votes
28 down votes
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Strategic Goal: Goal 3: Advance Translational Research

Building a bridge - new approaches to dissemination

There is a need to fundamentally rethink the approach to translation and dissemination of clinical trial results. The current approach relegates dissemination as a side effect to the end of a trial and does not require sufficient funds be set aside to conduct adequate outreach. As a result, it takes up to 17 years for the results of trials to be adopted and used in everyday practice. It is time for a new model which re-prioritizes ...more »

Submitted by (@media0)

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 benefits of clinical research on the quality of health are compromised by the slow and ineffective process by which they find their way into clinical practice. Decades of theorizing on the dissemination of scientific knowledge has resulted in overreliance on outmoded theoretical approaches to dissemination. Much of the work to date has the appearance of “victim blaming” (e.g., the characteristics of “slow adopters” are identified and many physicians are thought to evidence “clinical inertia”). Much less attention is focused on: a) the outmoded and ineffective process of dissemination itself, disregarding the important (even critical) role of the digital age and social media; b) the ever changing organizational contexts in which dissemination is supposed to occur (not considering the important role of the consumer or patient in dissemination); and c) the demonstrated efficiency of the private sector in disseminating information to organizations, providers and patients (commonly known as direct to consumer advertising). Delays in dissemination result in delays in receipt of new therapies, effective new approaches, safe and more cost effective treatments and contributes to social injustices which perpetuate health disparities.

Feasibility and challenges of addressing this CQ or CC :

Many federally funded clinical trials are completed with fastidious attention to scientific quality a key challenge is the relegation of dissemination to an afterthought, often unfunded and neglected. The feasibility of improving dissemination has been repeatedly demonstrated by the private sector driven by a need to complete trials rapidly for immediate dissemination and adoption (time to market). The challenge is to re-prioritize dissemination to be part of the entire clinical trial process (proposal to study close), and to create a separate funding requirement within PAs and RFPs to ensure that there is both a requirement and resources dedicated to dissemination. Conducting a consensus conference between the federal and private sectors to learn the best practices to improve dissemination while maintaining research quality is essential.

Name of idea submitter and other team members who worked on this idea : Lisa Marceau. Team Member: John McKinlay

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4 up votes
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Strategic Goal: Goal 4: Develop Workforce and Resources

Training of Clinical & Translational Scientists

Although the NCRR and NIGMS used to have a mechanism to train new generation of clinical & translational scientists, this program was stopped. Why?

What is the possibility of other institutes to come up with the priority of funding resources in this regard?

Submitted by (@dkagr0)

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 view of the health care models, strong control of insurance companies in determining the remuneration, lack of protective time for qualified clinicians to continue their research, no incentive to the institute for promoting such activities, lack of available tenure-track jobs, pool of effective and well-trained clinical & translational researchers is decreasing rapidly. Even though NIH invests resources to train MD-PhD students, a very minor pool of these graduates continue curiosity and passion in advancing new knowledge and discovering newer approaches.

Feasibility and challenges of addressing this CQ or CC :

1. Additional resources must be developed by NHLBI, NIAID, NIDDK and other major institutes to support this endeavor.

2. Institutes/medical schools who provide protective time to their faculty to continue their efforts in clinical & translational research, must be acknowledged and incentivized.

3. There has been no effective way of measuring outcomes from such investments. All of us must take ownership in utilizing the resources more effectively and more productively.

Name of idea submitter and other team members who worked on this idea : Devendra K. Agrawal, PhD

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Strategic Goal: Goal 1: Promote Human Health

Transforming Transplantation with RISC

What is necessary to reprogram the immune system to improve transplant outcomes of hearts, lungs, and hematopoietic cells? 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 ...more »

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 :

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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15 up votes
18 down votes
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