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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Goal 3: Advance Translational Research

Community Trials for Cardiovascular Health Enhancement

There is a need to initiate innovative community trials that are: theory-based; are integrated multi-component, multi-setting, and multi-level (i.e., they target individual, family, community, and built environment); engage community stakeholders; and use community-participatory research principles to enhance cardiovascular health (CVH) in vulnerable and diverse populations.

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 :

Global impact on cardiovascular health.

Feasibility and challenges of addressing this CQ or CC :

There are smaller scale community interventions but none in the literature that focuses on larger-scale multi-level trials as proposed here. This CQ would target vulnerable and diverse populations to reduce health disparities.

NHLBI supported the stroke belt initiative, and the exemplars in community CV health research: (e.g., the Stanford 5 City Project, The Minnesota Heart Health Program, The Pawtucket Heart Health). The next generation of community CVH research should harness the lessons from these studies, findings for the 8 Americas (Chris Murray), and numerous results from NHLBI cohort studies to implement large-scale community trials for cardiovascular health enhancement.

Resources for a large scale study could be a challenge. Ability to motivate a whole community, to prevent contamination, and to sustain interventions would be a challenge.

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

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-1 net votes
9 up votes
10 down votes
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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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9 net votes
15 up votes
6 down 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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2 net votes
15 up votes
13 down votes
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Goal 2: Reduce Human Disease

Clinical Trials & Duplicative Regulatory Standards

The initiation of clinical trials remains difficult, time-consuming, and costly. Repetitive institutional review board oversight is one of several obstacles to efficient clinical trial initiation and completion. New strategies for addressing duplicative regulatory standards are necessary to ease the initiation and completion of trials.

Submitted by (@skrenrich)

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 : Cystic Fibrosis Foundation

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5 net votes
6 up votes
1 down votes
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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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4 net votes
15 up votes
11 down votes
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Goal 2: Reduce Human Disease

Phase III efficacy trials of tuberculosis drugs

1) Phase III efficacy trials of new tuberculosis drugs (e.g., bedaquiline, delamanid, PA-824) that have shown promise in early phase studies for multidrug-resistant tuberculosis. 2) Phase III efficacy trials of new and existing tuberculosis drugs to development very short course regimens (3-4 months). 3) Phase III efficacy trials of new and existing drugs for treatment of latent tuberculosis infection in contacts of ...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 : American Thoracic Society member

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1 net vote
1 up votes
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Goal 3: Advance Translational Research

Increased receptivity to probative programmatic trials

We believe there should be greater openness to large, simple trials that answer clear questions of interest (e.g. does giving children more fruits and vegetables while changing nothing else lead to weight loss?; does eating breakfast regularly lead to weight loss?; etc.). The conduct of such trials may sometimes be expensive but can sometimes be only modestly costly if they are kept simple. However, it is difficult to ...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 :

While we do not mean for a moment that we should drift away from mechanistic science, we believe that there should also be openness to addressing some questions that are simple and perhaps even slightly dull, but can be unequivocally answered with a trial. In this way, beliefs can be converted to facts.

Feasibility and challenges of addressing this CQ or CC :

It is difficult to seek funding for such trials because reviewers want to see more testing of mechanisms, more physiologic outcomes, more testing of hypothesized mediating variables, and more exciting scientific hypothesis tests.

Name of idea submitter and other team members who worked on this idea : David B. Allison, Ph.D.; Kevin Fontaine, Ph.D.; Kathryn A. Kaiser, Ph.D.; Andrew W. Brown, Ph.D.; Edward C. Archer, Ph.D.

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0 net votes
1 up votes
1 down votes
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Goal 3: Advance Translational Research

Improving Drug Safety through Precompetitive Research

The lack of transparency in Pharma clinical studies and the incomplete knowledge of the effect of genetic profiles and pharmacological factors on drug toxicities are challenges in decreasing drug development costs and increasing drug safety.

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 :

Precompetitive research and collaborations directed at improving our understanding of the factors underlying adverse patient responses to investigational heart, lung, blood, sleep drugs will help to expedite the drug development process, increase probabilities of success and reduce product development costs.

Feasibility and challenges of addressing this CQ or CC :

Several public-private initiatives such as The Predictive Safety Testing Consortium and the Cardiac Safety Research Consortium are underway that address components of this problem. NHLBI can join existing initiatives or formulate its own. In either case, NHLBI’s participation as either an honest broker or a funding source will enable substantive progress on several fronts over a 5-10 year period.

Clinical safety complications and chronic exposure toxicities are a major cause of drug trial failures and recalls and thereby contribute to the high cost of pharmaceutical product development and the rising prices of commercial medicines. Safety problems can usually be attributed to the off-target biological effects of drug compounds or their metabolites. Reducing the safety risks associated with drug development will therefore require us to expand our knowledge around the pharmacological and pharmacogenomic factors underlying adverse safety events. Furthermore, adverse events that occur during clinical studies that are conducted by pharmaceutical companies are not usually shared publicly. This lack of transparency contributes to unnecessary inefficiencies and costs in the drug development process.

Mechanisms for minimizing safety hurdles in drug development include funding precompetitive applied research and promoting collaborations among companies to encourage sharing of clinical failure data.

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

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-4 net votes
13 up votes
17 down votes
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Goal 2: Reduce Human Disease

Life-Course Approach to Science

We encourage the NHLBI to include research focused on children as a priority in their strategic vision. We encourage them to consider the implications of a life-course approach, where childhood presents a unique opportunity to set the trajectory for health risk as an adult. This also implies that interventions targeting children may have the greatest impact on the population as a whole in the long term.

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 : American Society of Pediatric Nephrology (ASPN)

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2 net votes
2 up votes
0 down votes
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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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-1 net votes
6 up votes
7 down votes
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Goal 1: Promote Human Health

THE RELEVANCE OF PREVENTION TRIALS

Prevention trials, implemented to reduce or delay progression to overt disease in a population at risk to the disease, are an important approach to health promotion. Therapies shown to reduce disease severity in patients with a specific disease are obvious, but not the only, candidates for a prevention trial in populations at high risk for prevalent diseases (such as heart failure, diabetes, COPD, asthma in children). ...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 impact of implementing such trials is considerable. They will clearly address an important component of NHLBI’s mission with respect to effectiveness of therapies and behavioral interventions, and it has minimal and clearly definable overlap with commercial trials of specific therapeutic products. It will also provide an important public health focus – preventing disease or reducing the impact of disease processes, thus potentially reducing chronic care costs and increasing years of useful life.

Feasibility and challenges of addressing this CQ or CC :

The biggest challenge in designing and implementing prevention trials is identifying the target, “at risk” population most likely to develop the clinical disease from known biomarkers or early signs/symptoms. Increasing availability of large, population-based registries or databases maintained for other purposes provides a very cost-efficient mechanism to electronically screen and identify “at risk” individuals. The same mechanism may also facilitate implementation of pragmatic, electronically managed, cost efficient trials.

Name of idea submitter and other team members who worked on this idea : Sonja McKinlay other Team Members: Susan Assmann and Paul Stark

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7 net votes
10 up votes
3 down votes
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