Also note: Single Cell Studies in Aging Research (R21): (PA-11-321)
Details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-321.html
Components of Participating Organizations
National Institute on Aging
Application Receipt/Submission Date(s): Multiple dates, see announcement.
The primary aim for this Funding Opportunity Announcement (FOA) is to encourage the submission of research projects that would advance biomedical research at the single cell level, facilitating the identification of molecular and cellular markers of normal aging and in disease progression during aging; and to advance the understanding of the impact of cellular heterogeneity during aging across a broad range of cell types and disease states.
Cellular behavior has traditionally been investigated by utilizing bulk-scale methods that measure average values for population of cells. Such population-wide studies mask the behavior of individual cells and are often insufficient for characterizing the biological processes in which cellular heterogeneity plays a key role. Populations of cells are almost always heterogeneous in function and fate. Cell heterogeneity is a feature that is intrinsic to many cell-fate processes, including cell division, apoptosis, and the generation of induced pluripotent stem cells. Cell signaling and transcription are also dynamic, often resulting in heterogeneous responses among cells. To understand fully the cellular specificity and complexity of tissue microenvironments under physiological conditions, it is necessary to measure molecular signatures with single cell resolution. By studying single cells at the molecular level it will be possible to obtain fingerprints of bioprocesses from different cell types and disease states and to assess how individual cells change the response to various challenges by altering the level of these biological processes in a cell-unique, yet coordinated manner. The insights into the biology of single cells will have important implications for the study of tissue and organ homeostasis during aging.
New technologies are making it possible to probe gene expression, DNA integrity, protein damage, and organelle structure and function in individual living cells with high sensitivity in real-time. Hence, the effects of aging at the single cell level are just beginning to be understood. Stochasticity in the age-related degeneration of metabolic, cellular and regulatory pathways could lead to large variation between individual cells in old age. These alterations have been implicated as a cause of aging and disease.
Nonetheless, it is clear that we can only study the fluidity of changes during aging by knowing the effects of variation in single cells on the physiology of the whole tissue. Single cell studies can be used to profile the state of the cell at many levels. DNA sequence of the genome of a single cell reveals the effects of spontaneous DNA mutations. RNA Seq experiments show variation in gene expression, ChIP seq experiments show variation in chromatin structure and transcription factor binding, and single cell proteomic studies show variation in protein levels between cells. These studies inform us about how cell variation changes the capacity of the cell to respond to outside influences and are necessary to provide an understanding of the phenotypic plasticity that exists in every cell. Another source of single-cell variation is that noise in these pathways may propagate with time resulting in high variation between individual cells in old age. Variability in individual cells within a tissue in old age may impede their ability to function in a coordinated manner, and could be an underlying mechanism for physiological decline of tissues. On the other hand, cell-cell variability could benefit old tissues by acting as a buffer or capacitor. Cell-cell variability in old age may allow individual cells to react to environmental stresses in a more robust fashion.
How can one assess the impact of cell-cell variability on mechanisms of aging? Current methodologies exist to describe DNA, RNA and protein level differences between different cells. But how does this variation affect aging itself? What are the physiological and mechanistic implications from cell-cell variability? These key questions need to be addressed if single cell studies are to give mechanistic answers regarding causality and not merely phenomenological correlations. Further progress is needed in generating an integrated system level approach to the analysis of multiple parameters in live native tissues (rather than dispersed cells).
NIA would welcome new directions in aging research that make use of single cell approaches in multi-cellular model systems. Areas of interest and appropriate topics in aging research include but are not limited to:
characterization of cellular heterogeneity in aging tissues,
understanding the response of individual cells to tissue damage and repair during aging,
characterization of single molecule and sub-cellular organelle dynamics in aged tissues,
identifying changes in tissue structure/function during normal aging and in age-related diseases,
understanding cellular communication and cell-cell interactions in aged tissues,
determination of cellular complexity in an old tissue or organ,
assessing the natural history of cells in the same tissue/organ/animal.
Investigators interested in developing new tools and technologies for single cell analyses should inquire with other NIH Institutes and Centers about their interest in supporting such research activities. It is expected that many of the projects submitted in response to this FOA will be collaborative efforts between and among investigators with different perspectives and backgrounds and with significant interests and expertise in the tools and technologies for single cell analyses and expertise in aging research.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.
Complete details at: http://grants.nih.gov/grants/guide/pa-files/PA-11-320.html.
EARLY CYSTIC FIBROSIS LUNG DISEASE STUDIES IN HUMANS, NHLBI (R01): (RFA-HL-12-035)
Components of Participating Organizations
National Heart, Lung, and Blood Institute
Application Receipt Date(s): January 11, 2012
Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in those persons with European ancestry. Repeated infections, lung damage, and respiratory failure are the most common complications leading to death. In the twenty years since discovery of the gene encoding CFTR, there has been significant progress in understanding the structure and function of CFTR, how mutations disrupt CFTR function, and the infection and inflammation that destroy the CF lung. Advances in survival have been realized with treatments directed at established disease in older children and adults, however we now have an opportunity to preempt and prevent CF lung disease earlier. Mechanisms and potential reversal of the early origins of CF lung disease have scarcely been explored.
Emerging evidence suggests that lung disease (namely, bronchiectasis, infection) begins early in infancy (3 months of age) and is initially “silent,” with substantial airways disease existing in the absence of overt signs and symptoms of a progressive disease process. Intervening during infancy or early childhood could potentially delay or prevent irreversible lung disease and improve CF survival and quality of life, but this will require early detection of disease in pre-symptomatic infants and young children. Hence, early markers of lung disease and appropriate end-points to establish disease severity, course of disease, and response to therapy are needed. The new frontier in CF is to detect and characterize disease in infants and young children before clinically observable signs or symptoms, at stages where irreversible lung damage is minimal and therapeutic intervention may be most effective. It is currently unclear how to detect, much less treat, this pre-symptomatic disease of infants and young children, and there is no clinical trial evidence base to guide therapeutic strategies in infants and children less than 6 years of age. Thus, better knowledge of pathogenesis in the early stages of life is also needed for identification of new therapeutic targets and outcome measures. Definition of the initial pathologic events will likely reveal improved strategies to delay or prevent early airway infection, inflammation, and structural remodeling (bronchiectasis), the major causes of morbidity and mortality in CF.
Universal newborn screening, conducted within the first days of life, now allows identification of most pre-symptomatic infants with CF by 2 to 6 weeks of age compared to 2 to 3 years previously. This screening provides unprecedented opportunities for identifying pre-symptomatic cases of CF, investigating mechanisms of CF lung disease at a very early stage (under 6 years of age), monitoring the progress of the disease longitudinally, and intervening in productive ways before irreversible lung disease develops. New technologies are now available to elucidate features of CF physiology, which can be adapted for use in infants. Potential lung disease biomarkers are known but need further validation to predict development and progression of CF lung disease. New animal models of the CF pulmonary phenotype are also in place and are providing insights that can inform human studies. These powerful new capabilities invite a new strategy of primary prevention and/or mitigation of CF progression in infancy and early childhood.
Research Objectives
To promote better understanding of early CF, this initiative will support up to 6 R01 grants that focus on the preclinical and early stages of lung involvement in this disease (birth to 6 years of age). The goals are to characterize the early origins of CF lung disease, elucidate mechanisms of disease development and progression, and identify targets and strategies for early interventions that will mitigate the pulmonary manifestations of CF. These objectives will likely require novel strategies for detection of early lung disease in infants and young children with CF, including minimally invasive biomarkers and/or imaging approaches that will predict the development and progression of pulmonary abnormalities and outcomes, as well as investigation of specific pathways related to these abnormalities that may be targeted by early interventions. Individual or combinations of relevant biological mechanisms may be studied, including but not limited to inflammation, infection, airway dehydration, ion transport, and abnormal epithelial function. Technologies for examining anatomic changes in early CF lungs (biomarkers and/or new imaging technologies) must be proposed in conjunction with mechanistic studies. Studies of humans will be required. Limited (not to exceed 25% of the proposed research scope) complementary studies conducted using newer animal models of CF may also be proposed. This program strongly encourages the forging of new collaborations involving multidisciplinary teams of investigators from a broad array of fields to develop novel strategies to elucidate mechanisms of early lung disease. Clinicians are encouraged to partner with experts in imaging and/or basic science to study structural changes in concert with functional abnormalities. Of particular interest are innovative studies using biological samples derived from CF infants and young children to detect gene x environment interactions that predict early lung disease (e.g., gene expression, proteomic, or metabolomic approaches); novel imaging approaches to detect early reversible lung disease (e.g., optical coherence tomography, etc.); and measures of altered airway defense and physiologic function (e.g., host-microbiome interactions, inflammation, repair, hydration, mucus properties, ion transport, progenitor cell dysfunction, etc).
Through this program, we expect to gain mechanistic understanding of the early origins of CF lung disease and to develop predictors and markers of its onset, progression, and severity in CF infants and young children. Additional goals include the identification of modifiable risk factors and of potential new targets for early intervention. Development of technologies and tools for characterizing lung disease that will enable examination of early CF lung disease pathogenesis, onset, and progression in humans will be allowed if required to address specific biological or clinical questions being asked in the research proposal. RFA meetings will be held yearly to enable investigators to share their successes and challenges, encourage collaborations, and promote sharing and consistency of data collection and analyses across the sites where appropriate.
SELECTED RESEARCH EXAMPLES
Research topics of interest include, but are not limited to those listed below:
Development of innovative strategies to detect and monitor early CF lung disease in humans and further elucidate mechanisms of origin and progression.
Identification of biomarkers (including minimally and non-invasive markers) of early CF lung disease onset, progression, and severity that reflect CF pathophysiology or predict response to treatment.
Identification of novel, safe imaging approaches to detect and track early CF airway abnormalities in humans.
Investigation of the associations of biomarkers and imaging measures with the onset, progression, and clinical outcome of pulmonary disease in infants and young children.
Evaluation of the magnitude and distribution of early CF lung disease using imaging technologies in concert with measures of physiologic function to interrogate and dissect heterogeneity and reversibility of early CF lung disease.
Development of improved minimally invasive or non-invasive methods for determining early infection, injury, and impaired clearance in the lung (i.e., imaging and sputum/blood surrogate markers).
Exploration of the relationship and contribution of genotype, genetic modifiers, host-microbiome interactions, inflammation, and remodeling to functional and phenotypic consequences of early CF lung disease using an integrative approach.
Investigation of specific pathways and interventions related to the disease-associated abnormalities.
Determination of strategies that reverse early radiologic findings such as bronchiectasis.
Utilization of new technologies (SD-OCT, microbiome sequence signatures, microrheological analysis, video microscopy of glandular function/clearance) to elucidate the connection between structural changes and physiologic abnormalities.
Exploration of the role of CF modifier genes and associated variants (identified by GWAS) in early CF disease pathogenesis and disease outcome using integrated approaches with a focus on drugable targets and development of potential pharmacologic interventions via these pathways.
Investigation in CF animal models of specific pathways and early interventions related to the disease-associated abnormalities being investigated in human studies.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
Complete details at: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-035.html.
SILVIO O. CONTE DIGESTIVE DISEASES RESEARCH CORE CENTERS (P30): RFA-DK-11-022
Components of Participating Organizations
National Institute of Diabetes and Digestive and Kidney Diseases
Application Receipt Date(s): March 30, 2012
The objective of the Silvio O. Conte Digestive Diseases Research Core Centers (DDRCCs) is to bring together, on a cooperative basis, basic science and clinical investigators to enhance the effectiveness of their research related to digestive and/or liver diseases and their complications. DDRCCs are meant to integrate, coordinate, and foster interdisciplinary research involving the etiology, treatment, and prevention of digestive and/or liver diseases and related disorders by a group of established investigators actively conducting programs of important, high-quality research that relates to a common DD-relevant theme. Thus, the purpose of a DDRCC is to provide the capability for accomplishments greater than those that would be possible by individual research project grant support alone.
INSTITUTION AND RESEARCH BASE
A DDRCC must be an identifiable unit within a single university medical center or a consortium of cooperating institutions, including an affiliated university. An existing program of excellence in biomedical research in the area of digestive and/or liver diseases is a prerequisite for applying. This research must be in the form of NIH research projects, program projects, or other peer-reviewed research that is already funded at the time of submission of a center grant application. This currently funded research base provides the major support for the investigators who would benefit from shared resources. The body of research described as the research base includes only currently funded, peer reviewed research grants awarded to the applicant institution. These may be Federally or privately funded awards; training grants and fellowship awards are not considered part of the research base.
Focus, relevance, interrelationships, quality, productivity, and, to some extent, quantity, are all considerations in judging the adequacy of the research base.
The absolute level of support must be sufficient to warrant the addition of a Center, typically at least $3 million a year. Since “Facilities and Administration” costs vary considerably between institutions, these should not be included in the calculation of the research base. Although collaborations with investigators outside the applicant institution/consortium are encouraged, the research base includes ONLY support for the investigators at the applicant institution/consortium.
A DDRCC must have a central focus of research investigation. The central focus must be a gastrointestinal disease, group of diseases, or functional studies relating to digestive or liver diseases. At least one-half of the research must relate to this central focus. Examples of a gastrointestinal disease-related central focus of research investigation include, but are not limited to, inflammatory bowel disease, functional bowel disorders, pancreatic disease, liver disease, pediatric gastrointestinal disease, and AIDS in gastrointestinal disease. Examples of functional studies as the central focus include, but are not limited to, gastrointestinal motility, gastrointestinal hormones, role of the gastrointestinal tract in obesity, gastrointestinal physiology, or gene therapy for digestive or liver diseases.
Criteria for designating an investigator as a DDRCC “member” should be clearly defined. Subsets of members based on their degree of participation or other quantitative measures are acceptable. Suitable criteria include peer-reviewed independent funding, participation in DD-related research, and need for the use of core facilities.
CENTER STRUCTURE AND ACTIVITIES
Biomedical Research Cores
The DDRCCs are based on the core concept. Cores are defined as shared resources that foster productivity and benefit a group of investigators working to accomplish the stated goals of the Center. Cores should provide specialized technical resources, and instruction, and/or expertise that enhance the efficiency and productivity of Center members. The proposed core services should be ones that are not readily available, or are not cost-effective when supplied from commercial sources, or which are technically challenging or require specialized expertise, equipment or infrastructure. Each proposed core must be utilized by a minimum of two federally funded investigators.
When appropriate, core staff should provide instruction for investigators, laboratory personnel, or fellows to learn, and then become proficient in, technologies that will become part of the repertoire of the laboratory. Teaching new or complex techniques and methodologies is an important function of a core.
Proposed cores may be part of an institutional shared research core, such as a centralized animal facility. In such cases, the support provided by the DDRCC should be proportional to the use of the institutional research core by DDRCC members. When proposing the use of a shared facility, details about access, fee-schedules, and prioritization of Center members to the shared facility must be described.
In addition to providing products or services, a Core must ensure appropriate quality control and maintain a record of use. Limited developmental research is also an appropriate function of a core facility as long as it is directly related to enhancing the function or usefulness of the core and is not an undertaking that should more appropriately be funded through other mechanisms. Plans for responding to the changing needs of the Center members should also be a part of each core.
Two to five biomedical research cores are usually included in a Center. Examples of core services/resources include, but are not limited to, imaging facilities, transgenic and ES-cell animal units, and membrane, cell, or tissue preparation laboratories.
Administrative Core
Each Center must include an Administrative Core responsible for allocation and oversight of Center resources. The Administrative Core personnel provide support for the required External Advisory Committee and internal committee structure of the Center. Maintaining a Center website, providing editorial services, and housing the optional Clinical Component as well as overseeing the Pilot and Feasibility (P/F) Program, Named New Investigator (if requested), and Enrichment Program are all functions of the Administrative Core. The DDRCC Director, and the PD(s)/PI(s) of the application, must devote a minimum of 2.4 calendar months to the Center, and at least 1.2 of those months must be within the Administrative Core to ensure adequate oversight of the Center. A full-time administrator for each center, or several part-time positions, is usually required for successful management of the DDRCC. One or more Associate Directors should be named who will be involved in the administrative, scientific, or training efforts of the Center and who will serve as Acting Center Director in the absence of the Director. A process must be in place that would be used to recommend a successor to the Director, if a successor becomes necessary.
Clinical Component
Since the NIDDK is interested in translating the work supported by the DDRCCs into practical therapies for digestive and liver diseases, the optional Clinical Component can serve as a resource, a focal point, and a facilitator for this function. Investigators, therefore, need not be funded directly for clinical studies to use the services or expertise provided by the Clinical Component nor to justify the existence of this component. Providing the capability for translating basic research findings into a clinical setting is the ultimate goal of the Clinical Component.
This Clinical Component may exist as a part of a Core, such as the Administrative Core. Besides leading to a better understanding of the etiology and natural history of disease, clinical components might provide biostatistics support; enhance clinical study design; foster collaboration among researchers; aid in recruitment of subjects for clinical studies; support epidemiological studies in areas of digestive and/or liver diseases; or provide modest funding for tissue, DNA, or serum storage. In addition, a Clinical Component may help Center members to effectively address NIH policies concerning women, children, and ethnic minority population participation in clinical studies.
Pilot and Feasibility Program
The P/F program provides modest support (typically $10,000 to $50,000) for new initiatives or feasibility research studies. P/F projects are intended to provide support for investigators to collect preliminary data sufficient to support a grant application for independent research support. P/F studies may (1) provide support for new investigators; (2) encourage investigators from other areas of biomedical research to use their expertise for DD research; and (3) allow established DD-investigators to explore innovative new ideas that represent a significant departure from their ongoing, funded projects.
Named New Investigator (Optional)
Each DDRCC may request, in the budget for the Administrative core, salary support for a P/F project recipient whom they designate a Named New Investigator (NNI). Support for this individual is limited to 3 years and cannot exceed $90,000 per year, additional appropriate fringe benefits, and 80% effort. The individual selected must be named in the application and be a junior investigator and a permanent resident or US citizen. Individuals are eligible only once for this support. Subsequent candidates for this position are nominated by the Center and reviewed by its External Advisory Board. Appointment of the NNI is contingent upon the concurrence of the External Advisory Board and the NIDDK DDRCC program director.
Enrichment Program
The DDRCC may request limited support for an enrichment program under the auspices of the Administrative Core. Support for visiting scientists, seminars, and research forum are appropriate items for inclusion in an enrichment program. Also, limited travel support may be requested to allow DDRCC investigators to present scientific findings, to learn new laboratory techniques, to develop new collaborations, or to engage in scientific information exchange. Mini-sabbaticals to allow Center investigators to enhance their scientific and technical expertise are allowable expenses. In all cases, the enrichment program should further the overall aims and objectives of the DDRCC as well as its cores. Creative new programs, not precluded by NIH or NIDDK guidelines, are encouraged. While DDRCCs cannot support postdoctoral fellows, the environment fostered by the existence of the Center with its core facilities in conjunction with the enrichment program educational opportunities should serve to foster the careers of postdoctoral fellows and junior faculty.
Applicants should consult with NIDDK staff concerning plans for the development of the DDRCC and the organization of the application.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
eRA Commons
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.
Because a DDRCC has a large and complex administrative structure, the Program Director(s)/Principal Investigator(s) must have strong leadership abilities and demonstrated proficiency in managing large, multi-component projects. The DDRCC PD(s)/PI(s) must also be willing to participate in yearly meetings of the Center Directors and Administrators.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Only one application per institution is allowed.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the PHS398 Application Guide.
Only institutions at which there is an ongoing, strong base of digestive and/or liver diseases-related research are eligible. At least 50 percent of the already funded research base in a new application must be supported by the NIDDK. In renewal applications, the NIDDK-supported research base may be less than 50 percent due, typically, to a growing number of investigators entering digestive or liver disease research from other fields.
Applications for DDRCC grants must propose a theme for the Center that is relevant to digestive or liver diseases and is supported by the research projects which comprise the research base for the DDRCC. The research base grants should be summarized in accordance with the DDRCC guidelines found at http://www2.niddk.nih.gov/Research/Centers/CenterPrograms/DDRCCGuideTOC.htm in sample Exhibit III.
Scientific personnel and institutional resources capable of supporting the research base must be available. In addition, the institution and pertinent departments must show a strong commitment to supporting the Center. Such commitment may be provided as dedicated space, staff recruitment, salary support for investigators, dedicated or shared equipment, or other financial support for the proposed Center.
Each proposed Core must be utilized by a minimum of two federally funded investigators. A detailed description of each Core proposed must be provided, including a detailed budget and budget justification. A well-qualified Core Director must be named for each Core. The description of each Core should include a rationale indicating how it will support the Center’s research effort in a cost-effective manner. Facilities must be available for the primary needs of the DDRCC because funds for new construction are not available from the P30 grant.
Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-11-022.html.
SMALL BUSINESS INNOVATION RESEARCH TO DEVELOP NEW METHODS AND TECHNOLOGIES ABLE TO IDENTIFY INDIVIDUALS AT RISK OF DEVELOPING TYPE 1 DIABETES [T1D] (R43): RFA-DK-11-024
Components of Participating Organizations
National Institute of Diabetes and Digestive and Kidney Diseases
Application Receipt Date(s): December 22, 2011
Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing cells of the pancreatic islets of Langerhans and affects more than one million Americans, usually with onset in childhood or young adulthood. The disease markedly impairs quality of life and shortens lifespan as is associated with numerous complications including blindness, renal failure, painful nerve disorders, cardiovascular disease and amputation. In addition to its devastating toll in human suffering, T1D and its complications result in significant health care expenditures for families and constitute a major societal economic burden.
Early identification of T1D risk and the onset of autoimmunity provides the basis for a variety of major ongoing studies seeking to prevent or delay the disease. Already research on the natural history of the development of T1D in at risk neonates has shown that early identification of those at risk can foster early diagnosis of T1D and avoid life-threatening diabetic ketoacidosis DKA. Also, clinical trials are currently in progress to identify ways to prevent or reverse the autoimmunity of T1D. Investigators have used a combination of islet autoantibody positivity, autoantibody seroconversion, biomarkers of genetic susceptibility and beta cell functional assays as criteria to select individuals at high risk of developing T1D. However, current technology for identification of at risk individuals is costly, requires participation of research laboratories, and may not be suitable for public health screening that would ensue should effective preventative interventions be established. Methods for more efficient identification of individuals at risk of T1D who may be eligible for preventative intervention would include low cost, high-throughput, accurate and predictive assays/devices that could be used at the point of care level. Application of such technologies could facilitate and expedite testing when effective ways to prevent or delay T1D become available and would be essential for identifying individuals who can benefit from such treatments. Population based screening of individuals would be required as the majority of new cases of T1D (∼70–80%) have no affected relatives.
This initiative intends to stimulate and support innovative research at small businesses for the development of low cost novel assays and devices for predictive screening for T1D risk and autoimmunity using genetic, immune and metabolics markers. The development of these technologies would facilitate recruitment for clinical research focused on identifying environmental triggers of T1D, T1D natural history, and interventions to prevent T1D. It will also facilitate clinical implementation of measures subsequently proven effective in delaying or preventing T1D in those at risk. Use of such assays in organ donors could also facilitate provision of autoimmune pancreas to researchers.
Examples of topics relevant to this announcement include but are not limited to:
Development of techniques or products useful for predicting, preventing or delaying progression of diabetes, including tests for identifying patients at risk, and methods of monitoring disease progression.
High throughput - Point of care assays (reliable, accurate, cost-effective, highly sensitive/specific standardized having rapid turnaround time) for autoantibody detection and other immune parameters for autoimmune diabetes diagnosis and follow-up. This could also include newborn screening methods.
Point of care low cost /portable devices for pre-diabetes and diabetes diagnosis.
Development of methods to measure changes in the immune status that may be used as markers to follow the immune-modulatory activity and beneficial effect (beta cell mass preservation, reduction of inflammation at the target organ, etc) of agents tested in clinical trials for the prevention and/or treatment of T1D.
Development of non-invasive imaging as well as other methods/biomarkers for the in vivo measurement/ evaluation of pancreatic beta cell mass, function or inflammation for the in vivo diagnosis and prognosis of a pre-diabetic stage and subsequent follow-up.
Development of high throughput assays based on biologic pathways likely involved in the pathogenesis of diabetes that could be used to develop novel diagnostic systems/platforms.
Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria:
Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor;
Is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there can be no more than 49 percent participation by foreign business entities in the joint venture;
Is at least 51 percent owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States, or it must be a for-profit business concern that is at least 51% owned and controlled by another for-profit business concern that is at least 51% owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States, except in the case of a joint venture, where each entity to the venture must be 51 percent owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States; and;
Has, including its affiliates, not more than 500 employees.
SBCs must also meet the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. Business concerns include, but are not limited to, any individual (sole proprietorship) partnership, corporation, joint venture, association, or cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be referenced for detailed eligibility information.
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant organizations must complete the following registrations as described in the SF424 (R&R) SBIR/STTR Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD(S)/PI(s) must be with the small business concern at the time of award and during the conduct of the proposed project. For projects with multiple PD(s)/PI(s), at least one must meet the primary employment requirement. Occasionally, deviations from this requirement may occur.
The SF424 (R&R) SBIR/STTR Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PD(s)/PI(s), see Multiple Principal Investigators section of the SF424 (R&R) SBIR/STTR Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process, or service that, with non-substantive modifications, can be applied to a variety of purposes. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and any other HHS funding opportunity, including the SBIR and STTR Parent announcements.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II support, a Phase I awardee should submit a Phase II application within the first six due dates following the expiration of the Phase I budget period.
In Phase I, normally, a minimum of two-thirds or 67% of the research or analytical effort must be carried out by the small business concern. The total amount of all consultant and contractual arrangements to third parties for portions of the scientific and technical effort generally may not exceed 33% of the total amount requested (direct, F&A/indirect, and fee).
The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or Phase II will be the total of the requested costs attributable to each party, unless otherwise described and justified in “Consortium/Contractual Arrangements” of the PHS398 Research Plan component of SF424 (R&R) application forms.
Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-11-024.html.
NIH DIRECTOR’S TRANSFORMATIVE RESEARCH AWARDS (R01): RFA-RM-11-006
Components of Participating Organizations
NIH Roadmap Initiatives
Application Receipt Date(s): January 12, 2012
The goal of the NIH Director’s Transformative Research Awards initiative is to provide support for collaborative investigative teams or individual scientists who propose transformative research projects, which, if successful, would have a major impact in a broad area of biomedical or behavioral research. To be considered transformative, projects must have the potential to create or overturn fundamental scientific paradigms through the use of novel approaches or to lead to major improvements in health through the development of highly innovative therapies, diagnostic tools, or preventive strategies. Consistent with this focus, applications supported under the Transformative Research Awards initiative will reflect ideas substantially different from mainstream concepts.
Several key features of this FOA have been designed to emphasize to applicants and peer reviewers that these applications are very different from conventional, investigator-initiated research awards. The application format, through its page limitations for sub-topics and requirements for explicitly addressing specific issues, focuses attention on the importance of the problem, the novelty of the hypothesis and/or the proposed methodology, and the magnitude of the potential impact rather than on experimental details. Reviewers will be instructed to emphasize significance and innovation in their evaluations, and these criteria will be the primary basis for funding decisions. These features are intended to steer applicants and reviewers, at each step of the process, toward the goal of this initiative, which is to solicit and fund unusually bold and potentially transformative research.
Projects in any area of NIH interest, including basic, clinical, translational and behavioral studies, are encouraged and will be considered responsive to this FOA. Though technical and conceptual risks are expected in highly innovative projects, clinical research also must contend with potential risk to human subjects. Clinical researchers should not be dissuaded from submitting applications as long as rigorous assessment of participant risk/benefit ratios compellingly indicates the ratio to be in favor of the potential benefit. Many of the advances in public health have been achieved through clinical trials, which necessarily involve some risk to participating human subjects. NIH acknowledges the presence of such risk and has established a set of clinical research ethics principles that provides guidance regarding the risk/benefit ratio in clinical research.
This Transformative Research Awards initiative is part of a series of programs known collectively as the NIH Common Fund programs (http://commonfund.nih.gov/). Common Fund programs are designed to foster new ways of doing research, to fill fundamental knowledge gaps, and to encourage risk taking to solve complex problems. The overarching criterion for Common Fund programs is that they are expected to substantially accelerate and enable research across the spectrum of health sciences. The NIH Director’s Transformative Research Awards initiative is a component of the Common Fund High-Risk Research Program that also includes the NIH Director’s Pioneer Awards, NIH Director’s New Innovator Awards, and the NIH Director’s Early Independence Awards.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government with the exception of NIH intramural investigators; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign institutions) are eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
Complete details available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-11-006.html.
NEURONEXT CLINICAL TRIALS (U01): PAR-11-343
Also note: NeuroNEXT Infrastructure Resource Access (X01): PAR-11-344
Details at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-344.html
Also note: NeuroNEXT Small Business Innovation in Clinical Trials (U44): PAR-11-345
Details at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-345.html
Components of Participating Organizations
National Institute of Neurological Disorders and Stroke
Application Receipt/Submission Date(s): December 2, 2011; April 2, 2012; August 2, 2012; December 3, 2012; April 2, 2013; August 2, 2013; December 2, 2013; April 2, 2014; August 1, 2014
In December 2010, FOAs (RFA-NS-11-009, RFA-NS-11-010, RFA-NS-11-008) were released for a Clinical Coordinating Center (CCC), a Data Coordinating Center (DCC) and a group of clinical sites, which combined will form the Neurology Network of Excellence in Clinical Trials (NeuroNEXT). This FOA provides one of a set of three different means by which teams of investigators can gain access to the NeuroNEXT infrastructure. This FOA uses the U01 cooperative agreement mechanism and is open to all eligible applicants, as defined in Section III. small businesses may wish to consider applying through PAR-11-345: NeuroNEXT Small Business Innovation in Clinical Trials (U44) (PAR-11-345). For-profit organizations and Non-profits other than Institutions of Higher Education may wish to consider applying through PAR-11-344: NeuroNEXT Infrastructure Resource Access (X01) (PAR-11-344).
This set of FOA’s encourages applications for biomarker validation trials or exploratory clinical trials of drugs, biologics, surgical therapies or devices that may contribute to the justification for and provide the data required to design a future trial to confirm efficacy (i.e., a Phase III trial). Applications for drugs or biologics should provide compelling scientific evidence that the investigational agent proposed for study will reach/act upon the designated target or that its mechanism of action is such that it will be of benefit in ameliorating a specific aspect of the disease. Neurologic diseases chosen for study must fall within the primary responsibility of NINDS (www.ninds.nih.gov/funding/areas/index.htm).
Examples of appropriate studies under this FOA include, but are not limited to, those designed to:
Evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity, pharmacodynamic response) in a human “proof of concept” trial
Select or rank the best of two or more potential interventions or dosing regimens to be evaluated in a subsequent trial, based on tolerability, safety data, biological activity, or preliminary clinical efficacy (e.g., futility trials)
Evaluate biological activity relative to clinical endpoints
Successful applicants will be given access to the NeuroNEXT infrastructure. The NeuroNEXT Clinical Coordinating Center (CCC) will work with the successful applicant to efficiently implement the proposed study. The NeuroNEXT Data Coordinating Center (DCC) will provide statistical and data management support. The NeuroNEXT clinical sites will provide recruitment/retention support as well as on-site implementation of the clinical protocol. Applicants do not need to be part of the existing NeuroNEXT infrastructure.
Applicants should make note of the following:
(1) Applicants to this FOA will be required to incorporate the NeuroNEXT infrastructure into their proposed study (www.ninds.nih.gov/NeuroNEXT). Additional (ad hoc) sites may be proposed to fulfill specific study requirements.
(2) The use of innovative and efficient study designs, such as adaptive designs and futility designs, is encouraged.
(3) This FOA is intended to support studies in patients, not healthy volunteers. All trials proposing use of an investigational agent or device must have an active IND or IDE.
(4) This FOA is not intended to support the conduct of a clinical trial where the primary aim is to demonstrate efficacy. Clinical/definitive efficacy should be evaluated in a Phase III trial: consider use of PAR-11-173, NINDS Phase III Investigator-Initiated Multi-Site Clinical Trials (PAR-11-173).
(5) This FOA is not intended to support the conduct of a clinical trial to estimate intervention effect size for use in power calculations for a future Phase III trial.
(6) The award and continuation of funding are subject to milestones to be specified in the notice of grant award according to NINDS policies.
There is increasing awareness among neurological disease communities that to assess the predictive value of preclinical research, sufficient information must be available about study design, execution, analysis, and interpretation. Examples of the critical elements of a well-designed study are summarized on the NINDS website (http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf). NINDS urges applicants to consider these elements when describing supporting data and designing the proposed studies.
Working with NeuroNEXT is a cooperative venture between NINDS, the NeuroNEXT network and the applicant. NINDS will provide guidance to potential applicants with input from the Office of Clinical Research, the applicable NINDS Extramural group and the NeuroNEXT Steering Committee Working Group. Potential applicants are strongly encouraged to contact NINDS OCR (see Agency Contacts, Section VIII) in order to discuss the feasibility of conducting the proposed trial through the NeuroNEXT infrastructure before submitting an application. Pre-application consultation may include an introductory teleconference (at least 3 months prior to submission), followed by a conference call or in-person meeting with NINDS staff, if needed.
The following activities are expected:
Pre-application/conceptual stage:
• Work with NeuroNEXT CCC and applicable patient representatives to review draft protocol/timeline of activities.
• Work with NeuroNEXT DCC and CCC to determine the number of potentially eligible participants at the proposed sites.
Start-up stage
• Finalize protocol, study procedure manual, and consent forms with assistance of the NeuroNEXT CCC.
• Working with the NeuroNEXT DCC, develop data management and quality control system.
• Working with the NeuroNEXT DCC, develop study case report forms (in conjunction with the CDE initiative http://www.commondataelements.ninds.nih.gov).
• Using the NeuroNEXT CCC, initiate contracts, start-up and training of study personnel at the proposed performance sites.
• If biomarkers are under evaluation, the applicant would be expected to submit a Letter of Intent to the FDA Biomarker Qualification Review team regarding the approved study to receive specific consultation and advice pertaining to future regulatory determination for “context-of-use.”
Completion stage:
• Complete enrollment and follow-up of all study participants.
• Minimize loss to follow up.
• Analyze data and submit study results paper for publication, within one year of completion of all subject follow-up.
• Provide public access to complete data set(s) within 18 months of study follow-up completion or after publication of the main study results paper, whichever comes first.
• Upon publication of the study results, the PD/PI will be expected to contact the FDA to discuss further steps needed, if any, for establishing context-of-use of study-identified biomarkers, when applicable.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities (foreign organizations) and components of U.S. organizations are eligible to apply, but will have to work with the U.S.-based NeuroNEXT infrastructure. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
It is not necessary that your institution be part of the NeuroNEXT infrastructure in order to be eligible to respond to this FOA; however your institution must agree to comply with the NeuroNEXT contractual arrangements.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-343.html.
SHORT COURSES ON MATHEMATICAL, STATISTICAL, AND COMPUTATIONAL TOOLS FOR STUDYING BIOLOGICAL SYSTEMS (R25): PA-11-351
Components of Participating Organizations
National Institute of General Medical Sciences
Application Receipt/Submission Date(s): Multiple dates, see announcement.
This FOA encourages applications from applicant organizations that propose creative and innovative research education programs to integrate mathematical, statistical, and computational approaches into biological, behavioral, and social sciences research. Progress in contemporary biological and behavioral disciplines depends heavily on investigators who are skilled in the use of mathematics, computation, and statistics (collectively referred to as quantitative methods). This is especially true for scientists engaged in multidisciplinary research, systems sciences, model development, and research on large and complex data sets. Many scientists wish to update their quantitative skills, learn new approaches, and/or become familiar with software and the language of quantitative sciences. They also need to understand the assumptions, advantages, and limitations of these approaches.
Likewise, many quantitative scientists are interested in applying their skills and knowledge to contemporary biological and behavioral research but may lack formal training in fundamental biological disciplines. These scientists could benefit from training in the goals, nature, issues, and language of biological research. This announcement encourages applications for short courses and workshops that will improve the knowledge and skills of (a) biologists and/or behavioral or social scientists in quantitative sciences and (b) quantitative scientists in biology and/or behavioral social sciences. Applications may address one or both of these areas.
Target communities may include undergraduate through professional levels. The needs of the target community and the programs goals should determine the instructional approach. These might include Web-based instruction or more traditional approaches, such as summer workshops or on-site instruction.
The National Institute of General Medical sciences (NIGMS) has a longstanding commitment to fostering a diverse and highly capable biomedical and behavioral research workforce that helps achieve the NIH mission. Therefore all applications must include plans to recruit a diverse group of students and faculty. The plan should specifically address recruitment and training for groups underrepresented in the sciences.
Although research education grants are not typical research instruments, they do involve experiments in education that require an evaluation plan in order to determine their effectiveness. A plan must be provided for program evaluation.
The NIGMS will consider applications for short courses and workshops that are focused on topics relevant to its mission (see http://www.nigms.nih.gov/About/Overview/). Courses and/or workshops may consider applying quantitative tools to the study of cells, tissues, and organisms from all developmental stages and to populations and social systems. Areas of interest may include, but are not limited to, the following:
Management and analysis of biological or behavioral data;
Visualization of data and modeling results;
Computational analysis and modeling of biological and behavioral processes within the NIGMS mission (e.g., biomolecular structure and function, modeling of regulatory networks, metabolism, developmental dynamics, physiology, pharmacometrics, multiple organ failure, social dynamics, evolution);
Statistical and quantitative methods applicable to biological research (e.g., quantitative genetics, genomics, or pharmacogenetics of human or model systems; statistical methods for high-throughput sequence data)
Topics of biological interest aimed at mathematicians, statisticians, and computational scientists, such as molecular and cellular dynamics, systems biology, genetics, pharmacodynamics, or population or social dynamics.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments; faith-based or community-based organizations, and regional organizations. The sponsoring institution must assure support for the proposed program. Appropriate institutional commitment to the program includes the provision of adequate staff, facilities, and educational resources that can contribute to the planned program.
Institutions with existing Ruth L. Kirschstein National Research Service Award (NRSA) institutional training grants (e.g., T32) or other federally funded training programs may apply for a research education grant provided that the proposed educational experiences are distinct from those training programs receiving NIH support. In many cases, it is anticipated that the proposed research education program will complement ongoing research training occurring at the applicant institution.
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
The PD(s)/PI(s) should be an established investigator in the scientific area in which the application is targeted and capable of providing both administrative and scientific leadership to the development and implementation of the proposed program. The PD(s)/PI(s) will be expected to monitor and assess the program and submit all documents and reports as required.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.
Researchers from diverse backgrounds, including racial and ethnic minorities, persons with disabilities, and women are encouraged to participate as faculty. Faculty should have research expertise and experience relevant to the proposed program. Faculty must be committed to continue their involvement throughout the total period of the mentee’s participation in this award.
Applications must describe the intended participants, and the eligibility and/or specific educational background characteristics that are essential for participation in the proposed research education program. Identify the career levels essential for participation in the planned program. Describe the training need for individuals in the target group(s).
Unless strongly justified on the basis of exceptional relevance to NIH, research education programs should be used primarily for the education of U.S. citizens.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PA-11-351.html.
RESEARCH USING SUBJECTS FROM THE TYPE 1 DIABETES TRIALNET NATURAL HISTORY STUDY (LIVING BIOBANK) (DP3): PAR-11-349
Components of Participating Organizations
National Institute of Diabetes and Digestive and Kidney Diseases
Application Receipt/Submission Date(s): December 7, 2011 and June 7, 2012
The NIDDK seeks to accelerate the pace of scientific research towards more effective prevention, treatment, or cure of type 1 diabetes. To this end, NIDDK is committed to providing access to research resources which will increase our understanding of type 1 diabetes pathogenesis in humans. This opportunity is intended to fund projects using subjects who have been phenotypically and genetically characterized for risk of developing type 1 diabetes through the Type 1 Diabetes TrialNet clinical research network.
The Type 1 Diabetes TrialNet is an international network of investigators, clinical centers, and core support facilities that recruits patients and conducts research to advance knowledge about type 1 diabetes and to test strategies for its prevention and early treatment. TrialNet supports the development and implementation of clinical trials of agents aimed at preventing the disease in at-risk patients and slowing the progression of type 1 diabetes in new onset patients. The network’s “Natural History Study” enhances understanding of how the disease develops in individuals at risk and thus helps in the formulation of future trials. The Natural History Study provides the basis for risk assessment and recruitment of at-risk subjects into clinical trials aimed at preventing the disease in susceptible individuals.
Currently there are two ongoing clinical trials for prevention in TrialNet. One is the Oral Insulin Trial which tests the ability of insulin taken orally to prevent the disease in subjects with moderate risk of disease. The other is the Anti-CD3 Prevention Trial which tests whether a course of teplizumab therapy can prevent the disease in high risk subjects. See the TrialNet website for more detailed information: http://www.diabetestrialnet.org/researchers/index.htm.
Identification of subjects at risk for type 1 diabetes requires enormous effort. Currently TrialNet screens nearly 20,000 relatives of people with type 1 diabetes annually to identify those with evidence of autoimmunity. The NIDDK seeks to obtain maximum value from this effort by expanding access to the population screened for mechanistic studies. This solicitation provides a means of accessing this unique at risk population as well as support for mechanistic studies in the population of subjects screened and monitored for type 1 diabetes risk in TrialNet. Mechanistic studies can be cross-sectional or longitudinal. Applicants may propose to perform tests on subjects and/or collect samples “on demand” from well-defined at risk populations identified through TrialNet. The FOA would support studies that seek access to participants in the Natural History Study or in prevention studies for sample collection or testing. Access to Natural History Study participants for mechanistic studies that may require some brief and safe intervention may also be proposed.
Studies funded by this FOA must not interfere with recruitment and participation of subjects in ongoing and approved clinical trials and studies within TrialNet. After the review of applications submitted in response to this FOA and prior to funding, the TrialNet Steering Committee will evaluate projects NIDDK is considering for funding for feasibility and potential impact on ongoing TrialNet studies as described below.
The TrialNet Natural History Study screens first and second degree relatives of persons with type 1 diabetes, and collects serum, RNA, plasma, and peripheral blood mononuclear cells (PBMC) every six months from enrolled subjects at risk for disease, and a smaller number of control subjects. It is anticipated that additional specific “on demand” samples could be collected at these regular visits or before and after a brief and safe intervention. A more detailed description of the schedule of assessments in the TrialNet Natural History Study and the ongoing and approved TrialNet clinical trials is provided here: (http://www.diabetestrialnet.org).
Exploratory research related to understanding type 1 diabetes pathogenesis in humans is encouraged if the question is significant and the investigators are well qualified. Small exploratory pilot studies to gather information relevant to type 1 diabetes prediction and prevention are encouraged. All research funded by this opportunity must use subjects enrolled in or screened for the TrialNet Natural History Study or in the prevention trials described above.
This FOA is not intended to fund clinical trials to test efficacy of interventions for type 1 diabetes prevention or treatment. Efficacy endpoints include C-peptide preservation or insulin dose, for example. Other funding mechanisms, including TrialNet (http://www.diabetestrialnet.org/researchers/index.htm), are available for the development and implementation of clinical trials with clinical efficacy endpoints. Clinical pilot studies involving safe interventions of short duration, involving a minimal number of subjects, and using mechanistic endpoints, are allowed under this FOA.
This FOA is not intended to fund studies using samples currently stored in the TrialNet or NIDDK or any other samples repository. Other funding mechanisms (http://grants.nih.gov/grants/guide/pa-files/PAR-09-247.html and http://grants.nih.gov/grants/guide/pa-files/PAR-11-350) are available for ancillary studies using non-renewable longitudinal stored samples.
Applicants must explain how the proposed research will take advantage of the associated clinical and phenotypic data and why the proposed research specifically requires subjects from the TrialNet Natural History Study. Applicants must describe the TrialNet data that will be needed to select subjects and/or to analyze results obtained by their project. All investigators may apply to this FOA, whether outside or within the TrialNet consortium. All investigators are strongly advised to visit the TrialNet website http://www.diabetestrialnet.org/researchers/index.htm and to contact NIDDK staff (listed below) for assistance in applying to this FOA.
Examples of projects include but are not limited to:
New technology for measurement of biomarkers of type 1 diabetes in peripheral blood, including correlates of: disease susceptibility, environmental triggers, autoimmunity, disease progression (including measures of beta cell mass or function);
Evaluation of blood glucose excursions in persons at high risk for type 1 diabetes using continuous glucose monitoring to better understand dysglycemia, especially in its earliest stages and as it progresses to overt clinical symptoms or diagnosis;
Minimally invasive, targeted imaging of pancreatic inflammation or beta cell mass in persons at high and low risk of developing type 1 diabetes, with or without a short course of anti-inflammatory intervention;
Evaluation of vaccine responses in persons with type 1 diabetes risk;
Evaluation of changes in immune parameters in response to short term treatment with immunomodulatory drugs;
Measuring functional correlates of type 1 diabetes risk, assays requiring special collection techniques or specimens not currently collected in TrialNet.
Applications should include:
Background and rationale for study;
Specific objectives, including how the results would be integrated with other study results, and the impact of the results on understanding disease pathogenesis, progression, or potential response to treatment;
Study details, including the number of subjects required and subject characteristics;
Request for funding only for studies involving subjects enrolled in or screened for the TrialNet Natural History Study;
Amount and type of samples if appropriate, variability and quality control characteristics of any proposed assay or test, expected effect sizes and group differences, a statistical plan with calculations to demonstrate that the number of subjects and samples will be sufficient to answer the question;
Plans for sample management, including return to the TrialNet repository of any unused specimens;
Plans for data management, recognizing that data generated from any study funded by this FOA will be shared with the TrialNet consortium and the public through the NIDDK repository according to current NIH data sharing guidelines. In many studies utilizing samples, the applicant can remain blinded to subject identity using masking identifiers by the TrialNet Coordinating Center. However, if subject identity cannot be blinded, or an intervention is planned, a plan for human subjects protection including local IRB review and review by Data and Safety Monitoring Board (DSMB) may be required (see NIH guidelines for clinical research) (see also below under review criteria). If review by a DSMB is required, applicants may use the established TrialNet DSMB;
Budget request. It is expected that this FOA will attract project proposals with a wide range of budgetary requirements, from small exploratory studies requiring few samples and inexpensive collections to larger or more complicated studies with more expensive tests. Small exploratory studies with costs below the budget limits published in the FOA are encouraged. Applicants should request, in addition to funding for their own lab, funds for selected costs incurred by the TrialNet Coordinating Center, specifically related to the proposed study and outside of normal TrialNet screening and monitoring. Tables are provided at the TrialNet public website (http://www.diabetestrialnet.org/researchers/index.htm) to assist applicants in estimating these extra costs. For example, if a study requires an additional collection at the next scheduled TrialNet monitoring visit, there will be no need to budget for costs related to the scheduled visit, but some of the costs of obtaining the additional samples should be requested (i.e., payment for a blood draw on a capitated basis, cost for a specific collection tube, and cost of shipping samples to the assay lab; estimates of these costs are provided on the TrialNet website). Studies that require additional visits outside of those normally scheduled by TrialNet will need to budget for the costs associated with additional visits, including patient travel. If the proposed study will require subjects to visit to a specific location for a specific test (for example, an imaging study), patient travel should be included in the request. No costs should be requested for staff salary at the TrialNet clinical sites. Costs associated with data collection (case report forms) for data types currently collected by TrialNet do not need to be requested, but if the data or sample collected is new, some costs should be requested. Funds should be requested for analyses or reports performed by the TrialNet Data Coordinating Center. Costs budgeted for TrialNet Coordinating Center activities are only estimates. Exact costs will be determined in negotiation with NIH program staff for those applications with a priority score within funding range.
The TrialNet network committees, as appropriate depending on the complexity, risk, and scope of the proposed research, will review all applications receiving a score in a fundable range to ensure that the proposed research is safe, feasible, will not interfere with ongoing or approved clinical trials for type 1 diabetes prevention, and will not impose too great a burden on subjects or network operations. Institutional Review Board approvals from the relevant clinical sites will be required for any interventional study. These reviews will be accomplished before any awards are issued. Additional information from applicants may be requested after review.
If a proposed study requires FDA approval under an IND, NIDDK will hold the IND and lead the negotiations for approval. Awards will be held until FDA approval (if required) is obtained.
See Section 6. “Other Submission Requirements” below for detailed application instructions specific to this FOA.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-349.html.
RESEARCH USING BIOSAMPLES FROM SELECTED TYPE 1 DIABETES CLINICAL STUDIES (DP3): PAR-11-350
Components of Participating Organizations
National Institute of Diabetes and Digestive and Kidney Diseases
Application Receipt/Submission Date(s): December 7, 2011 and June 7, 2012
The NIDDK seeks to accelerate the pace of scientific research towards more effective treatment and prevention of type 1 diabetes and its complications. To this end, NIDDK is committed to providing access to research resources including biosamples repositories and databases from type 1 diabetes clinical trials. This activity will support investigations on non-renewable (non-DNA) samples generated by selected studies and clinical trials.
There are two ways to access samples. One is through the NIDDK Central Repository (www.niddkrepository.org) which contains samples from the following type 1 diabetes clinical trials: Type 1 Diabetes Prevention Trial- 1 (DPT-1), and Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC samples collected though 2001). The second way to access samples is through one of the following NIDDK-funded consortia:
Type 1 Diabetes TrialNet, (http://www.diabetestrialnet.org/index.htm); or the Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications DCCT/EDIC (samples collected before and after 2001), (http://www.t1diabetes.nih.gov/investigator/details.asp?ConsortiumID=36).
This opportunity is limited to research using samples from the clinical trials or studies listed herein. Funding or access to samples will not be provided for assay development or exploratory animal models research. Investigators should propose to test scientifically meritorious hypotheses related to the clinical trial’s goals. Applications should explain in what ways the study is meritorious, the assay technique is validated, and demonstrate that the laboratory is able to carry out the assays with the highest quality standards.
Applications that propose to use consortium-controlled samples must include in their application a document that clearly indicates that the consortium has granted approval for access to the samples. Applicants must apply to the consortium through the relevant ancillary studies application process (links below) with sufficient time for consortium review prior to the FOA receipt date (at least 6 weeks prior to receipt date). This letter must be included with the grant application for the application to be considered complete.
Studies using NIDDK Repository-held samples will be reviewed both for access approval and funding at the same time through this FOA. Applicants must visit the NIDDK Repository, https://www.niddkrepository.org/niddk/jsp/public/sampleInstruction.jsp, register for a login and password, and make a preliminary application for access to samples. The Repository will then provide a standardized report which will indicate that samples are present in sufficient number and quantity or volume for the study. This report must be included with the grant application or the application will be considered incomplete and will be returned without review.
Nature of the Research Opportunity
The FOA is expected to promote scientific discoveries on disease mechanisms, disease pathogenic processes, and biomarkers of disease progression or clinical responses. Applicants must explain how the proposed research will take advantage of the associated clinical and phenotypic data, and why the proposed research specifically requires samples from the selected trial or clinical study. This FOA will provide funding to support scientific collaboration among assay providers from outside of the clinical trials networks and clinical and laboratory scientists and biostatisticians within NIDDK’s consortia listed above. Consortia member scientists are encouraged to submit applications, but they must also have documented access to consortium-controlled samples through the relevant process.
Applications should include:
Background and rationale for request of these limited, irreplaceable, and valuable clinical samples. Analysis of additional samples from other studies is allowed if it is well-justified and important for understanding the specific clinical studies listed below;
Specific objectives, including how the results would be integrated with other study results, and the impact of the results on understanding disease progression or response to treatment;
Assay details, including amounts and type of samples, assay variability and quality control, expected effect sizes and group differences, a statistical plan with calculations to demonstrate that the available samples are sufficient to answer the question;
Documentation from the relevant clinical consortia confirming that access to samples has been approved, or documentation from the NIDDK Repository that requested samples are available;
Budgetary information is required. It is expected that this FOA will generate applications with a wide range of budgetary requirements, from small studies utilizing few samples to larger studies with more expensive testing. Budgets should include repository charges (see the repository website https://www.niddkrepository.org/niddk/home.do for access charges by sample type).
Plans for sample management, including returning any unused specimens, plans for data sharing (data are expected to be shared with the consortium or the repository source, consistent with the goals of this program) and future directions.
See Section 6. “Other Submission Requirements” of the full announcement for detailed application instructions specific to this FOA.
The following is a brief description of clinical trials and studies with opportunities for samples access and testing.
The Type 1 Diabetes TrialNet is an international network of investigators, clinical centers, and core support facilities that recruits patients and conducts research to advance knowledge about type 1 diabetes and to test strategies for its prevention and early treatment. TrialNet supports the development and implementation of clinical trials of agents aimed at preventing the disease in at-risk patients and slowing the progression of type 1 diabetes in new onset patients. The network’s “Natural History Study” enhances understanding of how the disease develops in individuals at risk and thus helps in the formulation of future trials. The Natural History study provides the basis for risk assessment and recruitment of at-risk subjects into clinical trials aimed at preventing the disease in susceptible individuals, see weblink for publications from TrialNet: (http://www.diabetestrialnet.org/publications/publications.htm). TrialNet samples available under this FOA are described below. Applicants must apply for access to samples using ancillary studies application procedures: http://www.diabetestrialnet.org/researchers/ancillary.htm.
a) The TrialNet Natural History Study collects serum, RNA, plasma, and PBMC every 6 months from enrolled subjects at risk for disease, and a smaller number of control subjects. Samples from selected subjects within the Natural History study will be made available. Check the TrialNet website (link above) for specific information about the available collection, and for instructions on how to apply for access.
b) The Mycophenolate Mofetil-Daclizumab (MMF/DZB) clinical trial tested whether two immunosuppressive drugs used in combination, MMF and DZB, could stop the ongoing destruction of beta cells in new onset type 1diabetes patients, relative to MMF alone or placebo control. The clinical trial was stopped early when it became clear that the drugs were not able to stop the decline in C-peptide production (Diabetes Care. 2010 Apr;33(4):826-32.). Samples that potential collaborators may apply for include PBMC, whole blood RNA, and serum. Check the TrialNet website for specific information about the available collection, and for instructions on how to apply for access.
c) The Anti-CD20 trial tested the effects of the drug “rituximab”• (anti-CD20) on progression of type 1 diabetes in new onset patients. This randomized, double-blind study used rituximab to deplete B cells and tracked the decline in C-peptide over 2 years (primary endpoint at 1 year). The study showed a statistically significant maintenance of C-peptide production at 1 year in type 1 diabetes patients that received the active drug compared to placebo (N Engl J Med. 2009 Nov 26;361(22):2143-52.), although the effect waned at the two years. Samples that potential collaborators may apply for includes serum, plasma, PBMC and whole blood RNA. Check the TrialNet website for specific information about the available collection, and for instructions on how to apply for access.
d) The CTLA-4-Ig trial tested the effects of the agent “abatacept” (CTLA-4-Ig, Orencia) on progression of type 1 diabetes in new onset patients. Abatacept interferes with the activation of T cells by binding to the molecules CD80/86 (expressed on antigen presenting cells) and blocking their interaction with the co-stimulatory receptor CD28 (expressed on T cells). This double-blinded, placebo control trial showed that abatacept, given monthly, delayed the decline of C-peptide (a measure of beta cell function) relative to placebo controls (Lancet. 2011 Jun 28). Samples that potential collaborators may apply for include serum, plasma, PBMC and whole blood RNA. Check the TrialNet website for specific information about the available collection, and for instructions on how to apply for access.
e) The GAD-alum trial (randomized, blinded, and placebo controlled) tested whether 2 or 3 spaced vaccinations using GAD protein in alum, relative to alum alone, could delay C-peptide decline in new onset subjects. GAD-alum was predicted to modulate the antigen-specific immune response to GAD antigen, through either response type skewing or induced regulation, and to thereby interfere with pathogenesis. The study showed no difference between either of the active drug dosing arms, and the placebo, in the primary or secondary outcome measures at 12 months (Lancet. 2011 Jun 28). Samples that potential collaborators may apply for include serum, plasma, PBMC and whole blood RNA. Check the TrialNet website for specific information about the available collection, and for instructions on how to apply for access.
f) The Anti-IL-1 beta (canakinumab trial) is currently in progress and will determine whether inhibition of the IL-1 inflammatory pathway can delay the decline of C-peptide in new onset T1D patients. This is a double-blinded, placebo controlled trial with the primary outcome at 1 year (expected in May, 2012). Samples that potential collaborators may apply for include serum, plasma, PBMC and whole blood RNA. Check the TrialNet website for specific information about the available collection, and for instructions on how to apply for access.
DPT-1: The Diabetes Prevention Type 1 (DPT-1) trial was a multi-center randomized clinical trial to determine if treatment with a common beta-cell auto-antigen (insulin) can delay the onset of Type 1 Diabetes Mellitus (Type 1 DM) in relatives of persons with type 1 diabetes. The protocol for high risk subjects used daily subcutaneous insulin injections and an annual course of intravenous insulin treatment (N. Engl. J. Med, 2002 May 30;346(22):1685-91), while the protocol for intermediate risk subjects used daily doses of insulin or placebo administered orally (Diabetes Care, 2005 May;28(5):1068-76.) There were over 100,000 relatives of persons with type 1 diabetes screened, and 711 subjects entered either the parenteral or oral arm of the study. Serum samples were collected and will be available from subjects who enrolled in the trial(s), some of whom later developed type 1 diabetes. Samples from a selection of subjects (over 10,000) who were autoantibody negative at screening are also available. A data set is available and applicants are urged to obtain and review the data to assist in their preparation of the application. Information for obtaining data and a samples availability report from this study is available on the NIDDK Repository Website: https://www.niddkrepository.org/niddk/home.do.
The Diabetes Control and Complications Trial (DCCT) recruited 1,441 type 1 diabetic participants who were randomly assigned to 2 treatment groups, intensive and conventional, for an average of 6.5 years of randomized treatment time. The DCCT ended in 1993 after demonstrating conclusively that intensive treatment reduced the development and progression of diabetic retinopathy, nephropathy and neuropathy, compared to conventional treatment. Subsequently, the Epidemiology of Diabetes Interventions and Complications Study (EDIC) recruited 96 percent of the living participants from DCCT for regular observational follow-up of metabolic and complications status, using similar methods as in the DCCT. The former intensive treatment group continues to exhibit the same reduction in the risks of diabetic complications, starting from a new baseline. This carry-over effect of prior glycemic exposure on the later course of complications (superimposed on the effect of concurrent glycemic exposure) has been called “metabolic memory.” Serum, plasma and urine samples have been obtained annually since the DCCT baseline and stored frozen at −70°C. Samples collected through 2001 are available through the NIDDK Repository and may be applied for under this FOA. A data set is available and applicants are urged to obtain and review the data to assist in their preparation of the application. Information for obtaining data and a samples availability report from this study is available on the NIDDK Repository Website: https://www.niddkrepository.org/niddk/home.do.
The ongoing DCCT/EDIC research group also welcomes proposals for collaborative studies from any investigator who believes he/she has a research idea that could utilize some of the stored sample collection (serum, plasma and urine) and clinical phenotypic data in an ancillary study. Any proposal would receive initial review by the relevant DCCT/EDIC committees, and would have to abide by the policies and procedures for data sharing and publications described here: http://www.niddk.nih.gov/patient/EDIC/edic.htm.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-350.html.
PILOT AND FEASIBILITY CLINICAL RESEARCH GRANTS IN KIDNEY OR UROLOGIC DISEASES (R21): PAR-11-352
Components of Participating Organizations
National Institute of Diabetes and Digestive and Kidney Diseases
Application Receipt/Submission Date(s): Multiple dates, see announcement.
The Division of Kidney, Urologic, and Hematologic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has a longstanding and substantial interest in clinical research concerning the prevention and treatment of kidney diseases and urologic disorders. This funding opportunity announcement (FOA) specifically encourages the submission of applications for small scale or pilot and feasibility clinical and translational research studies, including epidemiological studies or clinical trials related to kidney or urologic disease research that address important clinical and translational questions. It is anticipated that some applications for pilot and feasibility studies may lead to full-scale clinical studies including evaluation of diagnostic strategies, epidemiologic studies, or trials in the diagnosis, prevention, or treatment of kidney or urologic diseases.
These grants may be used to plan, evaluate the feasibility, or implement clinical trials that assess pharmacological, dietary, surgical, or behavioral interventions for the prevention or treatment of kidney or urologic disease.
It is anticipated that applications submitted in response to this FOA will focus on kidney or urologic clinical studies. Basic laboratory research, studies of laboratory animals, studies that do not involve human subjects or are not human studies should be submitted via the Parent R21 (PA-11-261: http://grants.nih.gov/grants/guide/pa-files/PA-11-261.html).
Recent estimates of chronic kidney disease (CKD) in the US population, obtained through analysis of the Third National Health and Nutrition Examination Survey (NHANES III), indicate that it is a common medical problem, affecting over 26 million people in the US, and that its prevalence in the US has increased significantly over the last decade. Most cases of CKD observed in the US occur in the setting of diabetes, hypertension, glomerular disease and polycystic kidney disease.
With the increase in CKD, the incidence of end-stage renal disease (ESRD) has also been steadily increasing in the adult US population. The substantial morbidity and mortality experienced by ESRD patients and persons with earlier stages of CKD remains unabated. The increasing rate of ESRD has also markedly increased waiting time for cadaveric transplantation such that the rate of kidney transplants per patient year on dialysis has steadily declined by 47%, from 5.7 per 100 dialysis patients in 1990 to 4.0 in 2008.
Acute kidney injury (AKI) in hospitalized patients is also a significant and increasing problem in the US. Medical management of acute kidney injury has traditionally consisted of supportive care, with renal replacement therapy implemented for the most severe cases. Despite such interventions in AKI, however, mortality rates in affected patients remain very high (>50% in some series).
In view of these observations suggesting a high prevalence of CKD, and increasing ESRD and AKI in the US population, NIDDK has sponsored a number of large, multi-center studies of specific kidney disorders. These studies include prospective investigations in chronic kidney disease, dialysis access, polycystic kidney disease, focal and segmental glomerulosclerosis, and acute kidney injury. In planning and performing these studies, however, it has been apparent that the process for identifying appropriate interventions for both single and multi-center trials in kidney disease must be improved. This is particularly evident in the current small number of clinical studies related to kidney disease that could ultimately be expanded to large-scale clinical trials.
Urological diseases and disorders inflict a significant impact on the health care burden of the United States. The NIDDK funded Urologic Diseases in America Project (UDA) has published data on 16 of the most important urological diseases. Some urologic conditions are common in the US population, such as urinary tract infection, which afflicts 13 percent of adult females and 2 percent of adult males each year at a cost to the US health care system of over $3 billion. Urinary incontinence is very common in the elderly (60 and over) with 38 percent of females and 17 percent of males reporting some level of incontinence. Although the direct medical costs of incontinence are not great, the morbidity associated with incontinence and the indirect costs to persons with this condition are significant. Similarly, benign prostatic hypertrophy (BPH) associated with lower urinary tract symptoms (LUTS) is very common in older adult males, with almost one-quarter of men over age 50 reporting symptoms of some kind. As with incontinence, BPH does not result in large direct medical care costs but does result in considerable morbidity and substantially reduced quality of life. Urolithiasis, or kidney stones, is both common and a source of considerable pain and health care costs. Five percent of Americans will have a symptomatic stone at some time in their life and the annual health care costs are over $2 billion.
Information on the burden of other non-malignant urological diseases and disorders such as erectile dysfunction, the chronic pelvic pain syndromes such as chronic prostatitis and interstitial cystitis, and the many congenital and acquired pediatric urological disorders is not as complete but available studies suggest that these conditions are common and increasing, burdensome and costly.
The morbidity of many of these non-malignant urological disorders is often exacerbated by other common co-morbid conditions such as diabetes and obesity. Advancement in accurate diagnosis, prevention and treatment of these diseases is hampered by many factors including a lack of well-validated methods to access disease progression, by a lack of insight into the genetics of the disorders, absence of well formulated and tested definitions of the disease and its possible clinical subcategories, by a lack of rigorous epidemiological data and by an incomplete understanding of the pathophysiology of many of these diseases and disorders. In addition, in many cases the armamentarium of available diagnostic approaches has not been applied to these diseases.
The goal of this FOA is to provide flexibility for initiating preliminary, short-term studies, thus allowing new ideas to be investigated in a more expeditious manner without stringent requirements for preliminary data. Such support is needed to encourage new and experienced investigators to pursue new approaches, underdeveloped topics, or high risk research. If successful, these awards should lead to significant scientific advances in the treatment of kidney and urologic diseases.
As the kidney and urological diseases occur in a variety of clinical settings, and are associated with a number of co-morbid conditions, it is anticipated that applications submitted in response to this FOA could address a number of different aspects concerning the prevention, diagnosis, or treatment of patients with kidney and urological diseases.
Relevant topics of study evaluating kidney disease in adults or children could include (but are not limited to):
Diagnosis, epidemiology, disease progression, prevention or therapy of patients with, or at risk for, the following conditions:
Chronic kidney disease, including studies of diabetic nephropathy, hypertensive nephrosclerosis, polycystic kidney disease, or chronic renal allograft dysfunction
Glomerular disease, either idiopathic or secondary glomerular involvement in a systemic process
Acute kidney injury (excluding acute renal allograft rejection)
Co-morbid conditions associated with reduced kidney function
Studies assessing dialysis therapy, dialysis access, anemia of renal disease, nutritional or cardiovascular aspects of ESRD and other co-morbid conditions associated with ESRD
Relevant topics for study of the non-malignant urological diseases in adults or children could include (but are not limited to):
Diagnostic tools and instruments which can assess extent of disease, physiological parameters of disease and evaluate disease progression or response to therapy
Improved diagnostic criteria for diseases and disease sub categories
Accurate epidemiological data on diseases in various ethnic and racial groups
Validated strategies to access early detection of disease, for disease progression and for response to therapy
Novel approaches to preventing the onset of disease or preventing the progression of established disease
Studies of the effect of the treatment of co-morbid disorders on the symptoms, progression and morbidity of urological diseases
Environmental and modifiable risk factors which affect the development and/or progression of symptoms of non-malignant urological disorders
Exploration of urologic and other disorders which occur in early childhood which may affect development of urinary symptoms later in life
Validity of newly established or current diagnostic methods to predict response to treatment
The evolution and vitality of the biomedical sciences require a constant infusion of new ideas, techniques, and points of view. These may differ substantially from current thinking or practice and may not yet be supported by substantial preliminary data. By using the R21 mechanism, the NIH seeks to foster the introduction of novel scientific ideas, tools, agents, targets, and technologies that have the potential to substantially advance biomedical research.
The R21 mechanism is intended to encourage new exploratory and developmental research projects. For example, such projects could assess the feasibility of a novel area of investigation that has the potential to enhance health-related research. Another example could include the unique and innovative use of an existing methodology to explore a new scientific area. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, or applications that could have a major impact on a field of clinical research.
Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. For example, long-term projects, or projects designed to increase knowledge in a well-established area, will not be considered for R21 awards. Applications submitted under this mechanism should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or applications.
Eligible institutions and organizations include: public or state controlled institutions of higher education; private institutions of higher education; Hispanic-serving institutions; Historically Black Colleges and Universities; Tribally Controlled Colleges and Universities; Alaska native- and native Hawaiian- serving institutions; nonprofit organizations with 501(c)(3) IRS status (other than institutions of higher education); nonprofit organizations without 501(c)(3) IRS status (other than institutions of higher education); small businesses; for-profit organizations (other than small businesses); state governments; county governments; city or township governments; special district governments; Indian/Native American tribal governments (federally recognized); Indian/Native American tribal governments (other than federally recognized); eligible agencies of the Federal Government; U.S. territories or possessions; Independent School Districts; public housing authorities/Indian housing authorities; Native American tribal organizations (other than federally recognized tribal governments); faith-based or community-based organizations, and regional organizations. Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
Central Contractor Registration (CCR) – must maintain an active registration, to be renewed at least annually
Grants.gov
eRA Commons
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4–6 weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.
Complete details available at: http://grants.nih.gov/grants/guide/pa-files/PAR-11-352.html.