Showing 30 ideas for tag "biomarkers"

Goal 1: Promote Human Health

Developing tools/algorithms for objective evaluation of sleep health

What are the best tools/algorithms for robust and objective evaluations of sleep health biomarkers?

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 is pervasive in today’s society and associated with an array of threats to health and public safety. The availability of a biomarker(s) for sleep health would turn-the-curve on developing practical and feasible ways to identify individuals at risk for sleep deficiency and prevent/manage associated risks to health and public safety on a large-scale.

Feasibility and challenges of addressing this CQ or CC

Sleep and circadian regulation is coupled to an array of behavioral, physiological and molecular/genetic processes to leverage in the development of biomarkers for sleep health.
Untreated sleep disorders and sleep deficiency pose a significant burden on health and public safety. There is currently no biomarker, or point-of-care technology available to objectively measure an individual’s level of sleep deficiency or susceptibility, a significant barrier to prevention and management.

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

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124 net votes
162 up votes
38 down votes
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Goal 2: Reduce Human Disease

Biomarkers of Pulmonary Hypertension

What are informative and clinically relevant biomarkers of pulmonary hypertension (PH)?

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

Details on the impact of addressing this CQ or CC

This research emphasis would help identify novel pulmonary hypertension biomarkers of disease risk and progression that can be used for early detection or as outcome measures in prevention trials or treatment of PH, which is a disease currently still not curable with high mortality rate.

Feasibility and challenges of addressing this CQ or CC

NHLBI Division of Lung Diseases just launched the multi-center PVDOMICS research program last September that will enroll ~1,500 patients in the next 5 years for deep phenotyping PH. PVDOMICS will provide a perfect foundation and platform for this proposed featured study about informative and clinically relevant biomarkers of PH, and make answering this proposed question more feasible in the next 5-10 years.
Although significant advances in the treatment of pulmonary hypertension have been made in the past two decades, currently pulmonary hypertension remains a devastating disease without many clinically relevant and specific biomarkers available. Novel new informative and clinically relevant pulmonary hypertension biomarkers would greatly help advance the subtype-specific early diagnosis and precision treatment of this disease that could potentially decrease the mortality of PH.

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

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75 net votes
87 up votes
12 down votes
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Goal 2: Reduce Human Disease

Predictors of Sickle Cell Disease Severity

Can better predictors of disease severity such as specific biomarkers and/or genetic polymorphisms be identified so as to help understand the course and progression of sickle cell disease in various patients?

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 high clinical variability in sickle cell disease (SCD) and the lack of sufficient data to help understand and or predict the course of an individual’s disease warrants the identification of better predictors of disease severity. The identification of predictors of disease severity, such as biomarkers, will be vital in the management and treatment of SCD, especially since more recently several plasma biomarkers and certain genetic polymorphisms have been proposed to influence specific clinical outcomes, including stroke, sickle cell nephropathy, and survival. Furthermore, studies of biomarkers or genetic markers in the context of clinical drug trials may be helpful in predicting response rates, thus allowing for more personalized therapeutic decisions.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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58 net votes
76 up votes
18 down votes
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Goal 2: Reduce Human Disease

Personalized therapy of HCT complications

Can biomarkers make all the use of new predictive biomarkers enable earlier and more effective treatment of acute GVHD? Can biomarkers accurately guide reduction in therapy for patients who will respond to standard steroid treatment? Can biomarkers enable earlier and thus more effective therapy for high risk GVHD? Can new biomarkers (proteomic, genomic or a combination) also predict patients who are risk of relapse?

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

Details on the impact of addressing this CQ or CC

Despite enormous advances in immunology over the past several decades, there are no validated new therapies for acute GVHD, the major complication of allogeneic HCT. Several biomarkers have now been identified at the onset of GVHD that can predict response to treatment and provide a personalized profile of patients. But these biomarkers have not yet been used to guide therapy, and definitive clinical trials are needed to answer this question

Feasibility and challenges of addressing this CQ or CC

Need for consistent and accurate biomarker determination available for a large number of centers

Name of idea submitter and other team members who worked on this idea John Levine and James Ferrara

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74 net votes
99 up votes
25 down votes
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Goal 1: Promote Human Health

Understanding Individual Differences in Responses to Sleep Loss

Individuals differ substantially in their physiological, health, behavioral and cognitive responses to sleep loss. Although these differences represent a trait, individuals who are vulnerable in one domain may be resilient in another - few systematic relationships between physiological, long-term health, cognitive and subjective responses to sleep loss have been found. Moreover, within a given domain, vulnerability to... more »

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 this CQ is a sine-qua-non for individualized medicine. Especially in the case of physiological and long-term health responses to sleep loss, the differential vulnerability trait and the underlying mechanisms are not well characterized. However, as seen in the cognitive domain, investigating individual differences can help elucidate the underlying mechanisms. Thus, this should be a fruitful line of research not only in the context of individual differences per se, but also for better understanding the link(s) between sleep loss and adverse health outcomes in general.

Feasibility and challenges of addressing this CQ or CC

This CQ can be addressed by adopting a systems (neuro)biology approach in which individual differences are considered at the systems components level rather than the whole organism level. For example, the task-dependence of individual differences in vulnerability to cognitive impairment due to sleep loss may be investigated at the level of neuronal circuits that subserve performance of the task at hand, rather than at (or in conjunction with) the whole brain / genetic level. A significant challenge in this regard is that in the case of physiological and health responses to sleep loss, the differential vulnerability trait and the underlying mechanisms are not yet well characterized. See "Details On The Impact Of Addressing This CQ".

Name of idea submitter and other team members who worked on this idea 1

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124 net votes
171 up votes
47 down votes
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Goal 2: Reduce Human Disease

Understanding Cardiothoracic Surgery in Elderly Populations

There is a vital need for evidence-based clinical evaluation tools to assess operative risk and post-operative recovery in the elderly, including biomarkers of physiologic age and a simple/reliable clinical evaluation scheme to determine frailty as a risk factor for poor surgical outcomes.

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

Details on the impact of addressing this CQ or CC

Development of tools to assess operative risk and post-operative recover in the elderly would improve surgical outcomes in this growing patient population.

Feasibility and challenges of addressing this CQ or CC

This at risk population is growing rapidly.
Older patients represent an important, different, and under-studied subgroup of those undergoing cardiothoracic surgery according to the Joint NHLBI-AATS Working Group (http://aats.org/CME/2011-AATS-NHLBI-Symposium.cgi). Due to the aging of the US population and the increased severity of coronary and valve disease in older individuals, the use of cardiothoracic surgery in older patients in relative terms is growing rapidly. Between 1990 and 2008, the percentage of those aged 80 years or older has gone from 8% to 16% of total for bypass surgery and 14% to 30% of total for valve surgery.

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

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39 net votes
56 up votes
17 down votes
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Goal 3: Advance Translational Research

Maximizing Previous Investment in Existing Cohorts

Everyone would like to see integration of genomic, metabolomic, epigenomic, proteomic, transcriptomic, etc. data analyzed in the context of clinical disease, environmental influences, and even end-organ effects (lung versus heart or blood as an example). Rarely can this occur on small cohorts, but rarely are funds available to take maximum use of existing large cohorts and the samples and information collected within... more »

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 would be huge as it would leverage already extremely expensive cohorts to maximum potential, allowing for exploration into clinical subphenotyping, disease mechanisms, personalized medicine, surrogate endpoints, biomarker exploration, etc. Maximizine output on previous investment is the clearest impact, since even simple analysis in a large number of samples adds up to a very hefty sum. Additionally, data from samples becomes more valuable with longitudinal follow-up of available subjects.

Feasibility and challenges of addressing this CQ or CC

The challenges include the expense of analysis in large cohorts and the ability to attract and fund high level biostatistical faculty at top-notch institutions and get them engaged fully in the problem. Biostatisticians of high caliber will not engage without funding and without an ability to “train” students using the data and explore their own research interests within the context of the overall clinical problem. Funding mechanisms that are large (to allow for deep phenotyping of cohort samples on multiple platforms in multiple sample types) and that seek to generate solid and ongoing collaborations between the data generators and the data analyzers must emerge.

Name of idea submitter and other team members who worked on this idea Wanda K. O’Neal, PhD

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22 net votes
34 up votes
12 down votes
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Goal 2: Reduce Human Disease

Sleep quality assessments in health

Develop algorithms/chemistries (i.e. biomarkers) differentiating between sleep deficiency and health in point-of-care diagnostic evaluation of health risks.

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 NHLBI Staff

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37 net votes
56 up votes
19 down votes
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Goal 3: Advance Translational Research

Identifying Biomarkers of Chronic Lung Diseases

What are the biomarkers that identify expression and progression of specific subtypes of chronic lung disease?

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

Details on the impact of addressing this CQ or CC

Most chronic lung diseases, including COPD, do not have biomarkers that reflect disease pathogenesis accurately. Readily measurable biomarkers, especially in peripheral blood, would be key tools for clinical trials and studies of disease heterogeneity.

Feasibility and challenges of addressing this CQ or CC

The most useful chronic lung disease biomarkers would be proteins, metabolites, or gene expression measurements in peripheral blood. Defining useful peripheral blood biomarkers that reflect lung disease pathogenesis will require validation that the lung disease process can be captured in peripheral blood measurements.

Name of idea submitter and other team members who worked on this idea Ed Silverman, James Crapo and COPDGene Executive Committee

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42 net votes
62 up votes
20 down votes
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Goal 1: Promote Human Health

Venous Thromboembolism

How can individual VTE risk-assessment scoring be combined with promising biomarker candidates in order to help predict risk in the general patient population and prevent unprovoked low-risk VTE cases?

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 VTE field is approaching a new era of therapy in which predictive measures at the primary care level will identify those patients most at risk for VTE. With the identification of predictive biomarkers for VTE occurrence, efforts will be necessary to develop point-of-care or in-home biomarker testing devices to improve risk-assessment scoring and identification, so that patients could then be treated before progression. It will also be critical to accelerate risk-scoring systems that are beginning to incorporate biomarker candidates into the algorithm for use in clinical trials. Studies that will focus on correlating risk-assessment scores and biomarker research findings will provide a more accurate risk prediction and diagnostic value.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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30 net votes
41 up votes
11 down votes
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Goal 3: Advance Translational Research

Maximizing anti-tumor immunity following allogeneic HCT with biomarkers

Allogeneic hematopoietic cell transplantation (allo-HCT) is one of the most effective forms of tumor immunotherapy available to date. Allo-HCT can be life-saving for patients with aggressive malignancies that cannot be cured through other strategies. The immunotherapeutic efficacy of allo-HCT depends on donor T cell recognition of alloantigens on leukemic cells, which is known as the graft-versus-tumor effect (GVT). No... more »

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

Details on the impact of addressing this CQ or CC

Allo-HCT represents the only curative therapy for a number of malignant disorders but often results in serious complications, including GVHD. Because GVHD is such a potentially devastating post-transplant complication and because we want to be able to separate GVHD from the GVT effect, it is crucial to try to determine a specific biological pattern link to the favorable GVT effect. The focus of this critical challenge will be to develop a novel, non-invasive GVT signature in patients undergoing HCT. If successful, this will have a major impact, because a GVT-specific proteomic signature may facilitate the clinical therapeutic decision of rapid taper of immunosuppression or increased immunotherapies. The ability to identify patients who will not develop GVT early post-transplant has important therapeutic consequences, including preventative care with donor-lymphocyte infusion (DLI) or tumor-specific vaccines or T cells expressing chimeric antigen receptors (CARs). Equally important is the identification of patients who will develop GVT without GVHD, potentially enabling more rapid tapering of immunosuppressive regimens and thereby promoting even more the GVT reaction as well as reducing long-term toxicity in these patients. With this diagnostic tool, the HCT community may plan to develop preemptive therapeutic trials. In addition, the biomarkers may represent potential GVT-specific therapeutic targets to maximize GVT and/or immunotherapies.

Feasibility and challenges of addressing this CQ or CC

Using proteomics, several GVHD biomarkers were recently identified and validated. For example, high suppression of tumorigenicity 2 (ST2) plasma concentrations were significantly associated with the incidence of GVHD and transplant-related mortality in recipients of unmanipulated graft and cord blood transplants. Consequently, the Blood and Marrow Transplant Clinical Trial network is currently pursuing therapeutic interventions for newly diagnosed GVHD patients based on GVHD biomarkers risk-stratification. Thus, discovering and validating biomarkers post-HCT is feasible. However, the challenges with GVT-specific biomarkers are three-fold: 1) the absence of phenotype, as the only way to define clinical GVT without GVHD, is the absence of relapse and no GVHD post-HCT; 2) the paucity of samples to study GVT, ideally samples following DLI or nonmyeloablative conditioning preparative regimens that permit stable engraftment of donor hematopoietic cells but have little or no direct tumoricidal activity should be available; and 3) the relative lack of knowledge of the biology of GVT. These represent important challenges to solve. In sum, the recent successes of cancer immunotherapies, particularly for the treatment of hematological malignancies, have stimulated interest in the potential widespread application of these approaches, and biomarkers to predict and monitor the responses are required.

Name of idea submitter and other team members who worked on this idea Sophie Paczesny

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32 net votes
52 up votes
20 down votes
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Goal 2: Reduce Human Disease

Early COPD

What does early COPD actually look like. This is defined as severe COPD 30 years prior to its manifestation.

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

Details on the impact of addressing this CQ or CC

Prevention programs in COPD either target smoking or those with established disease. Better understanding the factors that lead to the development of COPD (both in ever and never smokers) is critical to improved disease prevention.

Feasibility and challenges of addressing this CQ or CC

We need to revisit long term studies in novel ways- and look at new cohorts. Better biomarkers need to be developed.

Name of idea submitter and other team members who worked on this idea Dave Mannino

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22 net votes
31 up votes
9 down votes
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Goal 2: Reduce Human Disease

Venous Thromboembolism

There is a great need for the development and evaluation of biomarkers for the study of venous thromboembolism (VTE) pathophysiology and risk assessment.

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

Details on the impact of addressing this CQ or CC

Recent efforts to evaluate biomarkers for VTE occurrence and recurrence have led to the identification of multiple potential candidates, including P-selectin, E-selectin, D-dimer, various microparticles, and various inflammatory cytokines. However, no specific biomarker has yet emerged for routine clinical use for individual VTE risk stratification and personal targeted therapeutics. The development of improved animal models will advance the study of VTE pathophysiology, allowing for more accurate evaluation of emerging biomarkers and initial assessments of potential advanced therapeutic interventions. Also, the identification and prioritization of novel VTE biomarkers will be needed to help improve our understanding of the molecular mechanisms underlying VTE, so as to shepherd the development of novel mechanisms of therapy beyond anticoagulation.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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13 net votes
26 up votes
13 down votes
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Goal 3: Advance Translational Research

Tools to facilitate availability and safe use of innovative blood products and their analogs

Novel blood products are being developed based on innovative science (e.g., ex vivo manufactured RBC and platelets, and platelet and plasma derived hemostatic products). However, there is a significant lag in the development of appropriate tools and model systems, which poses a challenge when evaluating such products for regulatory approval.

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 rapid advancement in science and technology has identified pathways for ex vivo manufacturing of RBC and platelets; platelet and plasma derived hemostatic products and recombinant coagulation factors, etc. However, these novel products have to be evaluated for their safety, efficacy, purity and potency as part of regulatory approval process. Because the new products are manufactured using innovative technologies some of the existing tools for their evaluation are inadequate. Therefore, future investments in the development of necessary predictive tools (I.e. regulatory science tools) in areas such as the following will positively impact the availability and safe use of innovative blood products and their analogs: 1) the development of analytical and biochemical assays, 2) animal models for product safety and efficacy, 3) product quality-associated biomarkers to characterize storage lesions of RBC and platelets and 4) functional assays and molecular and bioinformatics models that can predict the success of novel blood products both during manufacturing and with respect to clinical patient outcomes.

Feasibility and challenges of addressing this CQ or CC

This initiative is feasible as investigators in blood organizations, academia and government are already working independently towards this goal in their defined areas of study. However, a coordinated effort among these independent entities could help in the faster development of necessary regulatory science tools to optimize care of individual patients and patient groups.

Name of idea submitter and other team members who worked on this idea Office of Blood Research and Review, CBER, FDA

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12 net votes
17 up votes
5 down votes
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