Goal 3: Advance Translational Research

Obstacles to the timely completion of clinical trials

There are numerous obstacles to the timely completion of trials, and there is a crisis in US enrollment rates. Overcoming barriers to timely completion of clinical trials would have a profound impact on accelerating research translation to improving health. Clinical investigations are necessary to advance the prevention, diagnosis, treatment and cures of human disease. The rate of basic scientific discovery has overwhelmed ...more »

Submitted by (@rebecca.lehotzky)

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

Feasibility and challenges of addressing this CQ or CC :

For comparative effectiveness trials, incentives are misaligned; it is often easier, financially advantageous and benefits practice/hospital metrics to perform tests/procedures clinically than in the context of a trial. A collaboration between NHLBI, FDA and CMS would markedly accelerate many trials by aligning incentives. There are a few small examples with some success eg, Carotid stenting. Regulatory burdens should be reduced.

 

Solutions to enrollment challenges need to address physician and participant related barriers. NHLBI and AHA could lead a public private partnership and with patient advocacy groups (eg, Research America) and the media to enhance the understanding and acceptance of participation in clinical research.

 

To advance the efficiency of clinical trials NHLBI should support investigation of methodologies such as event driven trials, adaptive design, Bayesian approaches, multiple randomized groups, group/cluster randomized trials, maximizing information from subgroup analyses.

Name of idea submitter and other team members who worked on this idea : AHA Staff & Volunteers

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6 net votes
8 up votes
2 down votes
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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
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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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1 net vote
1 up 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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13 net votes
27 up votes
14 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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Goal 2: Reduce Human Disease

New models for clinical trials

There is a need to educate the scientific community and program staff about the use of metrics, results-based accountability, and other business models to improve the science, productivity, and efficiency of clinical trials and clinical trial networks.

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 :

Improve the efficiency of clinical trials and a return on research investments

Feasibility and challenges of addressing this CQ or CC :

Yes, this is feasible.

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

Voting

4 net votes
10 up votes
6 down votes
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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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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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Goal 2: Reduce Human Disease

How can we increase the pharmaceutical clinical research of targeted therapies in pediatric PAH patients, including encouraging

Clinical research, especially randomized pharmaceutical clinical trials, poses many unique challenges compared to research in adult subjects. In pulmonary arterial hypertension, a disease characterized by high blood pressure of the lungs with increased pulmonary vascular resistance leading to right ventricular failure, there are 12 FDA-approved PAH-targeted therapies for adults. None of these medications are currently ...more »

Submitted by (@katherinek)

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

Details on the impact of addressing this CQ or CC :

Pulmonary arterial hypertension is a heterogeneous condition generally characterized by high blood pressure in the lungs and increased pulmonary vascular resistance that leads to right heart failure if left untreated. Though some causes of PAH are seen in both adult and pediatric populations, some etiologies are seen exclusively in pediatric populations, including persistent pulmonary hypertension of the newborn, bronchopulmonary dysplasia, lung hypoplasia, and alveolar capillary dysplasia. Despite these differences in disease etiology, and known physiologic differences in pediatric populations, inhaled nitric oxide (iNO) in the acute setting is the only approved medication for PAH treatment in children. A number of issues have decreased pediatric PAH pharmaceutical research, including protection of the pediatric population as vulnerable subjects, principle of scientific necessity, balance of risk and potential benefit, parental consent/child assent, and feasibility of pediatric clinical trial design and implementation. Encouraging clinical trials of existing adult medications and potentially emerging, novel agents specifically for pediatrics—either through direct sponsorship or regulatory incentives—would not only lead to better outcomes for pediatric PAH patients, but potentially to a better and more comprehensive characterization of the developing pulmonary vascular system and right ventricle.

Feasibility and challenges of addressing this CQ or CC :

Several challenges exist for addressing this critical challenge. First, there are a number of differences between conducting clinical research in pediatric populations compared to adult populations. This not only includes the broad items referenced above, but items as noted by Rose and colleagues related to clinical trial design and analysis including (1) accepted age-matched normal ranges for laboratory values; (2) requirements for the validation of clinical endpoints for the assessment of efficacy and safety; and (3) standards for long-term safety monitoring and pharmacovigilance (Rose K, et al. NEJM 2005). Sponsorship of this type of clinical research is a second concern, which could either be mitigated by direct support from the National Institutes of Health of pediatric PAH clinical trials or in regulatory changes incentivizing pediatric clinical research in rare diseases.

Name of idea submitter and other team members who worked on this idea : Katherine Kroner, Michael Patrick Gray, PHA

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66 net votes
76 up votes
10 down 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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1 up 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 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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