Strategic Goal: Goal 2: Reduce Human Disease

Support for Cardiothoracic Surgery and Pediatric Heart Clinical Trial Networks

Continued and expanded support for the Cardiothoracic Surgical Trials Network (CTSN) and Pediatric Heart Network (PHN) is essential as both design, conduct, and analyze multiple, collaborative clinical trials that evaluate surgical interventions, and related management approaches for the treatment of cardiovascular disease. To date both networks have reported on and developed a portfolio of studies which need continued ...more »

Submitted by (@meaton)

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 work and support provided to date have allowed for the creation of an infrastructure for both the CTSN and PHN. Each network is now providing valuable results to the cardiothoracic surgery specialty which will allow an increase in quality patient care in the years and decades to come. The continued support is essential for the success of these networks as any reduction will limit the resources available for site participation and ultimately results. Due to the existing infrastructure for each network, the financial burden associated with de-funding and then restarting the networks in future years would be at least triple the financial commitment currently in place.

Feasibility and challenges of addressing this CQ or CC :

Conducting multi-center clinical trials is a substantial financial commitment but a vital part for the future of the cardiothoracic surgery specialty.

Name of idea submitter and other team members who worked on this idea : Matt E.

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108 net votes
151 up votes
43 down votes
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Strategic Goal: Goal 2: Reduce Human Disease

Towards Collaborative Funding of Clinical Trials

A way for clinical trial investigators to submit ONE application with ONE review and ONE funding decision, and the application would ask for funding from multiple funders (e.g. NHLBI and another IC, NHLBI and PCORI, NHLBI and AHA, NHLBI and CIHR, NHLBI and MRC).

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 :

It would be much easier for investigators from multiple sites/countries to secure funding for large-scale trials from multiple sponsors. They would only have to submit ONE application, respond to ONE review, and anticipate ONE funding decision.

Feasibility and challenges of addressing this CQ or CC :

Clinical trials have become increasingly difficult to afford, yet the need for them has never been greater. Many other sponsors (CIHR, PCORI, AHA, MRC, European Union) are eager to work with NHLBI to enable user-friendly multi-sponsor funding. Some similar type arrangements are already happening with other IC's (e.g. NINDS is working with CIHR and the UK MRC).

Large-scale clinical trials often require involvement of multiple sites, often located in > 1 country. Furthermore, the expense of trials often raises questions as to whether funders could collaborate, all contributing a certain amount. However, there is no simple user-friendly way for applicants to bring secure multiple sources of funding. Ideally, the division of funds would be agreed upon prior to application. In case of foreign funders, no monies would cross borders -- i.e. for NHLBI and UK MRC applications, the NHLBI would fund American sites while the UK MRC would fund UK sites, but all funding goes to ONE trial with ONE protocol and ONE data set.

 

One challenge would be politics. Who will do the review? NIH has traditionally acted as if it is the only agency capable to doing a valid review. Would NIH be willing to accept a review conducted by another sponsor? Would other sponsors be willing to accept a review fully run by NIH?

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

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-1 net votes
8 up votes
9 down votes
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Strategic Goal: 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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Strategic Goal: 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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Strategic Goal: Goal 2: Reduce Human Disease

Addressing low-level-evidence in cardiovascular guidelines

There is a need for the NHLBI to systematically assess CV guidelines that have public health importance and that can be addressed by pragmatic, government-funded trials.

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 :

A much greater proportion of CV guidelines which dictate practice standards would be based on high-quality scientific evidence.

Feasibility and challenges of addressing this CQ or CC :

Guidelines are already written and levels of evidence are already assessed (by others). Methods for conducting pragmatic trials exist (e.g. embedding in registries, leveraging digital resources, recognizing the importance of pragmatic trials within the clinical community).

More than 85% of active CV guideline are based on less than level 1A evidence.

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

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-7 net votes
2 up votes
9 down votes
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Strategic Goal: 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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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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9 net votes
15 up votes
6 down votes
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Strategic Goal: 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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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 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

New Clinical Research Methodologies for Rare Diseases

What innovative methodologies applicable to small cohorts and rare outcomes can better ensure the success of clinical and implementation studies in the rare diseases affecting heart, lung, blood, and sleep?

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 :

Efficient translation of clinical observation into discovery science, and, particularly, the timely translation of potential therapeutic target identification into the treatment of rare diseases has been impeded by the reality that rare disease populations are often too small to be studied using “classical” epidemiology, clinical trial, and implementation science methodology. Overcoming these barriers will require both the adaptation of current clinical research methods and the development of novel methodologies. The requirement for better methods in rare disease clinical science will become even more urgent with time as systems biology more specifically defines and sub-characterizes ‘common’ heart, lung, blood, and sleep disease populations

Feasibility and challenges of addressing this CQ or CC :

This problem has been recently addressed through special initiatives in the application of small trial methodology into the planning and design of clinical trials in rare hemostatic disorders and sickle cell disease. Furthermore, small clinical trial methodologists have begun to populate the CTSAs and Regulatory Agencies. Their expertise in clinical trial design and biostatistical methods, and their creative ideas can be brought to bear in the clinical trials required to advance NHLBI scientific priorities.

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

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24 net votes
37 up votes
13 down votes
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Strategic Goal: 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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