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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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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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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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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Goal 2: Reduce Human Disease

Optimizing Utilization of Composite and Repeat Endpoints in RCT

The use of win-ratio and other new statistical methods to analyze endpoints in new and existing clinical trials.

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 :

It could enable trials to be powered with smaller sample sizes. It can also be used to combine diverse information in a way to better guide clinical decisions.

Feasibility and challenges of addressing this CQ or CC :

The methodology exists and the need is growing as we try to sort out smaller treatment effects and our focus shifts from MI (which is fairly easy to define) to heart failure (which is more nebulous).

Traditional time-to-first endpoint analyses of clinical trials fail to capture the full impact of treatment in diseases with recurring endpoints (like heart failure hospitalization) or to capture the net benefit/risk of treatments with significant opposing effects (like the anti-thrombotic pro-bleeding effects of drugs like warfarin and dabigatran in atrial fibrillation or dual anti-platelet therapy after cardiovascular stenting), New statistical methods like the (win-ratio) when used together with patient- and clinician-based rankings of the importance of possible outcomes might provide a quantitative way to optimize the relevance of trials with multiple diverse endpoints to practical clinical decision making. I propose to encourage the use of these and other similar methodologies to analyze endpoints in new and existing trials. It would require a paradigm shift in how trialists look at endpoint data and in how regulators interpret trials.

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

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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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17 down votes
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Goal 2: Reduce Human Disease

Adequately powered clinical trials

Pragmatic and adequately powered clinical trials are an ongoing challenge.

­Develop new tools to facilitate identification and recruitment of subjects, remote/wireless data collection, and functional measures.

Submitted by (@societyforvascularsurgery)

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 : Society for Vascular Surgery

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4 net votes
5 up votes
1 down votes
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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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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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Goal 3: Advance Translational Research

T4 Translation Research Informing Early Stage Translational Research

There is a need to utilize insights gained from T4 translation research and implementation science to inform the design and execution of early-stage translational research and clinical trials.

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 :

• Assure that early stage translation research will be suitable for implementation in real world setting

• Aligns the research interventions from T1-T3 research to those appropriate to T4 research

• Potential to focus early stage research in key high burden areas

• Provides research community an understanding of the connections from early stage to late stage translation research which will potentially refine research strategies and directions at all levels

Feasibility and challenges of addressing this CQ or CC :

• Promote the importance of translation to population of heart, lung, blood, and sleep researcher to broader research community

• Potential for more T4 research contributions for guiding investment into translation research from T1-T3

• Provide avenues for T1-T3 investigators to translate their ideas into positive outcomes for population health

• Successful T4 research will stimulate feedback loop and identify opportunities for early translation research

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 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 1: Promote Human Health

Non-opioid management of pain

The use of opioid agents has increased dramatically in the United States. Prescription drug overdoses now account for more deaths than traumatic injuries in the 1-44 age group. There is a need for more high level evidence to target optimal pain management strategies in the acute (ED) and non-acute settings (office practice) especially for chronic disorders such as low back pain, headaches, fibromyalgia, acupuncture etc. ...more »

Submitted by (@dayam0)

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

Details on the impact of addressing this CQ or CC :

Huge problem in the US compared to other countries where opioid use is more restricted. Potential to enhance population health and reduce accidental death.

Feasibility and challenges of addressing this CQ or CC :

Complex since affecting by many factors and groups that would need to work together in conjunction with patients to change the way we approach pain.

Name of idea submitter and other team members who worked on this idea : Mohamud Daya

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