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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10 up votes
13 down 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 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 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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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

Assessing current methodologies for clinical trials

Are the current methodologies for clinical trials still the best practices for conducting efficient clinical trials?

Submitted by (@nhlbiforumadministrator)

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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10 net votes
16 up votes
6 down votes
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