Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Goal 2: Reduce Human Disease

Clinical Trials in Pediatric Sleep Disorders - Effect of adenotonsillectomy

Effect of adenotonsillectomy on behavioral and cardiovascular outcomes in children with primary snoring

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 recent NHLBI Childhood Adenotonsillectomy (CHAT) study showed highly significant behavioral improvements in children with obstructive sleep apnea syndrome . This study included children with an apnea hypopnea index as low as 2/hr. Many small or suboptimally controlled studies suggest that even primary snoring can affect behavior. If large randomized controlled trials confirm this finding, it will radically affect the treatment of the estimated 10% of children who snore.

Name of idea submitter and other team members who worked on this idea : ATS Member

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Goal 2: Reduce Human Disease

Moonshot: Turning the BMT EMR into a Research Record

The critical challenge is to develop a standards-based BMT electronic medical record (EMR) and integrate research capacity into the architecture of EMR systems. The ultimate goal would be to build de-identified complete data-sets which can be used to support observational studies and clinical trials, improve transplant outcomes and inform public policy.

Submitted by (@rakeshgoyal)

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

Details on the impact of addressing this CQ or CC :

Clinical research is constrained by a clumsy method of acquiring biomedical data, generally relying on manual capture of information from EMR back-to-paper which is then transcribed into registry or specific clinical trial databases. This method is labor intensive, fraught with opportunities for error, and increasingly difficult to defend in light of the high costs associated with clinical trials. Adoption of standards-based clinical documentation and creating access to source clinical data would reduce or do-away with resource-intensive, very expensive and time-consuming data abstraction, enhance data quality and depth, and accelerate translational research.

Feasibility and challenges of addressing this CQ or CC :

As BMT centers increasingly adopt EMR systems in the United States, a vast and potentially very useful data resource is being created. However, most EMR systems offer very generic formats for clinical documentation and the medical information is inconsistently expressed in vocabulary, structure, and format. One challenge is the development of common standards-based clinical documentation format and its adoption by EMR system vendors and BMT institutions to support structured data sharing.

 

Large transplant centers can build their own integration engines to link EMR with stem cell lab, HLA, donor care, workflow etc. However, a broad implementation of integration IT solutions would be needed amongst centers conducting BMT clinical trials.

 

While CIBMTR's FormsNet application and Clinical Trials Network allow electronic data submission, data professionals still need to manually enter the data. Another challenge in creating a centralized data resource would be to build interoperability between transplant centers and research entities. An alternative to a large centralized database could be a distributed research network which allows data holders to maintain logical and physical control over their data and mitigate security, proprietary, legal, and privacy concerns.

Name of idea submitter and other team members who worked on this idea : Rakesh Goyal

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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 2: Reduce Human Disease

Additional research needed to identify various contributors of obesity

What are the specific contributors of obesity that lead to chronic positive energy balance and surplus energy storage?

Submitted by (@mturner)

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

Details on the impact of addressing this CQ or CC :

Obesity is a health crisis of epic proportions. About 34% of adults in the US have obesity, up from 31 % in 1999 and about 15% in the years 1960 to 1980. The chronic diseases that result from obesity annually cost over $150 billion in weight-related medical bills. Reduction of obesity improves cardiovascular and other health outcomes, yet what is currently known about obesity is inadequate to combat the global obesity epidemic. A comprehensive understanding about the mechanics of obesity may help in developing more effective preventive and treatment strategies, which in turn will substantially improve cardiovascular and other health measures.

Feasibility and challenges of addressing this CQ or CC :

Years of obesity research have revealed the complex nature of this disease and its multi-factorial etiology. While research has firmly established the role of energy balance in weight gain and weight loss, it is important to discover upstream factors that predispose only certain individuals to energy imbalance. This may be addressed by further focusing on newly identified putative contributors of obesity, including but not limited to the impact of sleep deprivation, ambient temperature, age at first pregnancy, intrauterine and intergenerational factors, neuro-endocrine factors, epigenetics, environmental chemicals and endocrine disruptors, gut microbes, infections and the immune system, and social and behavioral factors associated with obesogenic behaviors. These studies may provide mechanistic insight that may also lead to the development of new pharmacological approaches. It is possible that cause-specific prevention or treatment approaches may yield more effective results than generic approaches that do not necessarily consider upstream modulators of energy imbalance, or inter-individual differences.

Name of idea submitter and other team members who worked on this idea : The Obesity Society

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Goal 2: Reduce Human Disease

Mechanisms of Uterine Hemostasis

What are the mechanisms of uterine hemostasis? Endogenous mechanisms of uterine hemostasis protect women from the bleeding challenges of miscarriage, childbirth, and menstruation. Dysregulation of these mechanisms has implications for the critical public health problems of hormonally-induced venous thromboembolism and hormonally-induced arterial thromboembolism (myocardial infarction and stroke). Our current understanding ...more »

Submitted by (@andra.james)

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

Details on the impact of addressing this CQ or CC :

Urgent clinical questions hinge on understanding the mechanisms of hormonally-induced thrombosis – questions about how women with various underlying cardiovascular conditions, hematological conditions such as sickle cell disease, and endocrinological conditions such as obesity are differentially affected by endogenous and exogenous hormones.

 

The additional impact of identifying the mechanisms of uterine hemostasis is potentially improving the global health problem of maternal and gynecological hemorrhage. If there is failure of normal uterine hemostasis after childbirth there is the potential for massive postpartum hemorrhage. If there is failure of normal hemostasis during the menstrual cycle there is the potential for acute heavy menstrual bleeding (acute menorrhagia).

Feasibility and challenges of addressing this CQ or CC :

An understanding of the mechanisms of uterine hemostasis provides the basis for understanding hormonally-induced thrombosis and vice versa. The paradigms of pregnancy; assisted reproductive technologies; contraception; and postmenopausal hormone replacement provide four clinical scenarios across the life cycle where female hormones or their synthetic counterparts provide opportunities for insight into mechanisms of hormonally-induced thrombosis. The NIH/NHLBI can and should support studies that elucidate the mechanisms of uterine hemostasis and hormonally-induced thrombosis and should make such studies a scientific priority. The NIH/NHLBI has the capacity and resources. Studies would include basic science, translational and clinical studies. Although studies would benefit from the participation of other institutes and from the contribution of multiple disciplines, NHLBI should take the lead.

 

Research efforts should be accompanied by cross-disciplinary training opportunities. The Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) program is a mentored career development program which connects junior faculty to senior faculty with shared research interests in either women’s health or sex differences research. Junior faculty are supported by institutions who receive grants from the Office of Research on Women's Health (ORWH) and BIRCWH program co-sponsors – multiple institutes which as yet do not include the NHLBI.

Name of idea submitter and other team members who worked on this idea : Andra James

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Goal 2: Reduce Human Disease

HEALTH CARE DISPARITIES IN DIAGNOSIS AND TREATMENT OF COMMON SLEEP AND CIRCADIAN DISORDERS

There is evidence of a higher prevalence of sleep and circadian disorders in different ethnic groups. This is true for both adult and pediatric subjects. There is also evidence that minority populations in lower socioeconomic groups do not seek evaluation for sleep disorders as frequently as other segments of our population. There is also evidence that they are less adherent to treatments such as nasal CPAP for obstructive ...more »

Submitted by (@jnoel0)

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

Details on the impact of addressing this CQ or CC :

Sleep disorders are more common in minority populations. Moreover, these populations have higher rates of the known consequences of these disorders such as stroke, myocardial infarction, hypertension, resistant hypertension. Despite this, current population studies such as the Sleep Heart Health Study have included only a very small percentage of African Americans. The impact of this would be the following:

 

a. Elucidating the basis of barriers to case identification in these group

b. Designing specific intervention to overcome these barriers.

c. Developing methods to improve adherence to therapy in this group.

d. Removing sleep and circadian disorders as a risk factor for consequences such as stroke, cardiovascular disease and resistant hypertension in minority populations

Feasibility and challenges of addressing this CQ or CC :

There is a developing interest in this area in the field of circadian and sleep research. There is a developing knowledge base about health disparities in sleep and circadian disorders. Minority institutions such as Morehouse have developing programs in this area. We also have mobile technology that facilitates study of sleep and circadian disorders in minority populations.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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Goal 2: Reduce Human Disease

Funding for Cardiothoracic Surgery Research

The continued development of new technologies requires cardiothoracic surgeons to maintain a strong level of research to ensure the highest quality of patient care and surgical outcomes are received across the world. The level of support for CT surgery within the NIH has continued to drop over the last decade. This is a substantial problem for the specialty as the limited funding available creates difficulty in the 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 :

CT Surgeons are performing procedures on some of the sickest patients while effecting some of the most dramatic favorable outcomes and the continue support for research in this specialty is essential to ensuring improvements in quality patient care. CT surgeons are provided the opportunity to participate in both the research lab and operating room which provides an important opportunity for a role in both the scientific discovery and implementation of new outcomes.

Feasibility and challenges of addressing this CQ or CC :

Cardiothoracic diseases are one of the top health issues facing the global population and the research being conducted is integral in helping cure the issues facing the current generation. With expanded support for research, new areas of the heart, lung, and esophagus can be studied with the hopes of identifying new technologies and procedures to help ensure the next generation is given the highest quality of care possible.

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

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Goal 2: Reduce Human Disease

Can Psychological Science Improve Weight Loss?

Will sensitivity to the psychological aspects of obesity, including lifestyle priorities and motivations, improve the efficacy of long-term effectiveness of weight loss and obesity prevention interventions?

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 :

A primary focus on principles of psychology may result in significantly improved control of the obesity epidemic. Effective interventions could reduce the risk of diabetes, sleep apnea, and hypertension. This research could also affect clinical practice guidelines for weight loss and obesity treatment.

Feasibility and challenges of addressing this CQ or CC :

Psychological science has been successful in developing effective treatments for a number of conditions, including sleep disorders, depressive symptoms, anxiety and phobias. Many of the behavioral principles employed in such interventions (e.g., cognitive restructuring, motivational methods) could be translated for the prevention and treatment of obesity within a reasonable time frame. Additional attention should be directed to the needs of population subgroups in which obesity is most prevalent.

In their Viewpoint article on weight loss intervention research, Pagoto and Appelhans (JAMA, 2013, see attachment) question whether a continued focus on dietary factors in research on weight loss and obesity is warranted. Their commentary raises the importance of attention to the individual psychological characteristics that influence adherence to weight loss interventions rather than dietary composition.

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 and Rare Diseases

Strategies and infrastructure to support clinical trials in rare diseases must go further in the development of critical partnerships with advocacy organizations. These partnerships must be formalized and based on models that help to accelerate the research.

Submitted by (@dappell)

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

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Goal 2: Reduce Human Disease

Clinical trial of AAT augmentation therapy in PI MZ subjects

Although severely alpha-1 antitrypsin deficiency (PI ZZ) individuals are rare, PI MZ subjects comprise approximately 3% of the US population. Mounting evidence suggests that PI MZ is a significant risk factor for COPD. A clinical trial of COPD exacerbation frequency using AAT augmentation therapy in PI MZ subjects with moderate-to-severe COPD could provide a rationale for AAT augmentation therapy (or small molecule neutrophil ...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 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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Goal 2: Reduce Human Disease

Image Repository

There is a need to digitize, remove identifiers, and archive, and catalog physical images, and to promote their use in clinical investigations.

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 :

Enable leveraging existing resources and possible re-purposing of existing resources to address a wide variety of research questions.

 

This is a cross-study, cross-NHLBI, and even cross-NIH or beyond, need.

Feasibility and challenges of addressing this CQ or CC :

Digitized imaging data files are enormous. Advances in data storage, with corresponding decreases in cost, have enabled storage of these files. For some types of images, data format standards have also arisen.

Many studies have collected data using a wide variety of imaging technologies. While the extracted data have been utilized in analyses and incorporated into shared data resources, additional research could be done on the original images.

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

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