Research on the Role of Nutrition and Diet in the Causation, Prevention, and Treatment of Cardiomyopathies and Heart Failure (R21)

Research on the Role of Nutrition and Diet in the Causation, Prevention, and Treatment of Cardiomyopathies and Heart Failure (R21) is sponsored by National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA), and Office of Dietary Supplements (ODS), NIH. This initiative renews a Funding Opportunity Announcement (FOA) to encourage exploratory or developmental research applications on the role of nutrition and diet in the causation, prevention, and treatment of cardiomyopathies and heart failure.

Expired PA-06-136: Nutrition and Diet in the Causation, Prevention, and Management of Heart Failure (R21) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Participating Organizations National Institutes of Health (NIH) ( http://www.

nih. gov ) Components of Participating Organizations National Heart, Lung, and Blood Institute (NHLBI) (http://www. nhlbi.

nih. gov ) National Institute on Aging (NIA), ( http://www. nia.

nih. gov/ ) National Institute of Nursing Research (NINR), ( http://www. ninr.

nih. gov/ ) Office of Dietary Supplements (ODS), ( http://dietary-supplements. info.

nih. gov/ ) Title: Nutrition and Diet in the Causation, Prevention, and Management of Heart Failure (R21) This is a reissue of PA-05-089 , which was previously released April 15, 2005. Update: The following update relating to this announcement has been issued: March 17, 2011 - This PA has been reissued as PA-11-166.

October 10, 2007 - Expiration Date adjusted to accommodate recent changes to standing submission deadlines, per NOT-OD-07-093. NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants. gov ( http://www.

grants. gov ) using the SF424 Research and Related (R&R) forms and SF424 (R&R) Application Guide. APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines provided with this announcement in Grants. gov Apply for Grants (hereafter called Grants. gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section Two steps are required for on time submission: 1) The application must be submitted to Grants. gov by 5:00 p.

m. local time (of the applicant institution/organization) on the 2) Applicants must complete a verification step in the (2) business days of notification from NIH.

Note: Since email can be unreliable, it is the responsibility of the applicant to periodically check on their application Program Announcement (PA) Number: Catalog of Federal Domestic Assistance Number(s) Release/Posted Date: March 3, 2006 Opening Date: May 2, 2006 (Earliest date an application may be submitted Letters of Intent Receipt Date(s): Not applicable Application Submission Date(s): http://grants1. nih.

gov/grants/funding/submissionschedule. htm Peer Review Date(s): http://grants1. nih.

gov/grants/funding/submissionschedule. htm#reviewandaward . Council Review Date(s): http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Earliest Anticipated Start Date(s): http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward .

Additional Information To Be Available Date (Url Activation Date): Not applicable Expiration Date: March 2, 2009 (now May 8, 2009 per NOT-OD-07-093 ) Additional Overview Content The purpose of this Funding Opportunity Announcement (FOA) is to encourage submission of investigator-initiated research applications on the role of nutrition and diet in the causation, prevention, and treatment of cardiomyopathies and heart failure.

Basic, translational, and applied interdisciplinary research applications with rigorous hypothesis-testing designs for projects in animals or humans are of interest.

The overall goal is to develop a satisfactory science base for preventive approaches in high-risk individuals and for rational nutritional management of patients in various This funding opportunity will utilize the Exploratory/Developmental (R21) grant mechanism, but will be run in parallel with a program announcement of identical scientific scope that will utilize the traditional research project grant (R01).

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications The total project period for an application submitted in response to this funding opportunity may not exceed two years.

Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year. Competing renewal applications will not be accepted.

Eligible organizations: Domestic, foreign, for profit and non-profit, public and private institutions such as universities, colleges, hospitals, laboratories, faith-based or community-based organizations, units of State Tribal government; units of Local Tribal government, and eligible agencies of the federal government.

Eligible Project Directors/Principal Investigators (PD/PIs): Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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 programs.

Applicants may submit more than one application, provided they are scientifically See Section IV. 1 for application materials. The SF424 (R&R) Application Guide for this FOA is located at these Web sites: http://grants.

nih. gov/grants/funding/424/SF424_RR_Guide_General_Ver2. doc http://grants.

nih. gov/grants/funding/424/SF424_RR_Guide_General_Ver2. pdf For general information on SF424 (R&R) Application and Electronic Submission, SF424 (R&R) Application and Electronic Submission Information: http://grants.

nih. gov/grants/funding/424/index. htm General information on Electronic Submission of Grant Applications: http://era.

nih. gov/ElectronicReceipt/ Telecommunications for the hearing impaired is available at: TTY 301-451-5936 Part I Overview Information Part II Full Text of Announcement Section I. Funding Opportunity Section II.

Award Information Section III. Eligibility Information 2. Cost Sharing or Matching 3.

Other - Special Eligibility Criteria Section IV. Application and Submission 1. Request Application Information 2.

Content and Form of Application Submission 3. Submission Dates and Times A. Submission, Review and Anticipated B.

Sending an Application to the C. Application Processing 4. Intergovernmental Review 6.

Other Submission Requirements Section V. Application Review 2. Review and Selection Process A.

Additional Review Criteria B. Additional Review Considerations D. Sharing Research Resources 3.

Anticipated Announcement and Award Dates Section VI. Award Administration 2. Administrative and National Policy Requirements Section VII.

Agency Contact(s) 1. Scientific/Research Contact(s) 2. Peer Review Contact(s) 3.

Financial/ Grants Management Contact(s) Section VIII. Other Information - Required Federal Citations Part II - Full Text of Announcement Section I. Funding Opportunity Description The purpose of this funding opportunity announcement (FOA) is to encourage submission of investigator-initiated research applications on the role of nutrition and diet in the causation, prevention, and treatment of cardiomyopathies and heart failure.

Basic, translational, and applied interdisciplinary research applications with rigorous hypothesis-testing study designs using animals or humans are of interest.

The overall goal is to develop a satisfactory science base for preventive approaches in high-risk individuals and for rational nutritional management of patients in various stages of heart Heart failure (HF) syndromes are frequently fatal illnesses in which the heart loses its ability to pump effectively in response to the body's needs.

HF is typically a chronic disease, with progressive deterioration of ventricular function occurring over a period of years or even decades. Patients may become incapable of performing even the simplest activities of daily living and are at very high risk of medical complications Congestive heart failure (CHF), the most severe clinical manifestation of HF, poses an enormous national public health burden. 4.

9 million Americans live with CHF. 550,000 new cases are diagnosed yearly, and the average duration of disease is ~9 years. In 2002 CHF accounted for 56,000 deaths, $15 billion in hospital costs, and $28 billion in total costs attributable to health care expenditures and lost productivity.

Elderly individuals are at particularly high risk of developing CHF; indeed, CHF is the leading hospital discharge diagnosis from medical wards among this age group. Systolic HF is the most common form found in the elderly. Diastolic HF also occurs frequently in the aged, presenting with dyspnea and decreased exercise tolerance Elderly women are the individuals who are most at risk of developing diastolic HF.

The influence of nutrition on HF phenotypes is poorly understood, although epidemiologic and mechanistic evidence is emerging that dietary factors and alterations in myocardial nutrient metabolism may play a critical role in the development and progression of the disease. This implies that dietary modifications might reduce risk of developing HF or might delay progression to more severe forms.

In addition, patients with advanced cardiomyopathies or CHF, including those treated by mechanical assist devices or cardiac transplantation, typically suffer from severe nutritional debilitation. Little guidance is available at present regarding optimal nutritional approaches for advanced cases, but dietary management represents a potentially cost-effective means of improving clinical outcomes for these patients.

Nutrition as a causal factor Nutritional factors have long been etiologically implicated in the development of cardiomyopathies, particularly in animals; the veterinary and agricultural literature provides a thorough documentation of multiple types of nutritional cardiomyopathies in species as diverse as swine, cats, dogs, foxes, rodents, and herbivores.

These primarily reflect dietary deficiencies or excesses of micronutrients such as vitamins or trace elements, sometimes in the context of dietary stress from protein restriction or high polyunsaturated fatty acid intake. Relatively little is known about the external factors that influence the development and severity of HF in humans.

In unusual situations, nutritional deficiencies may contribute to the development of human cardiomyopathy; one example is that seen in the interaction of coxsackie virus and selenium/vitamin E deficiency in fostering the development of Keshan disease.

Some cases of HF are attributable to agents that directly promote myocardial toxicity, such as excessive intake of alcohol, use of cocaine, or treatment with certain cancer chemotherapeutic agents. Most cases of HF, however, are linked to well-known risk factors for coronary artery disease.

The most striking of these is pre-existing hypertension, which appears to be both indirectly and directly linked to HF, as it is a risk factor for coronary artery disease and also is considered to result directly in the development of diastolic HF.

For relatively weak contributors such as diet or nutrition, the best way to obtain unbiased estimates of long-term risk is through the use of prospective cohort studies that enroll groups of healthy individuals and then track the development of disease over time.

In fact, recent evidence from large, long-term follow-up studies has suggested that dietary and nutritional factors can act as effect modifiers for risk factors such as hypertension, but also may have independent and possible causal effects on HF risk. The role of alcohol is not well understood, with relatively modest intakes appearing protective, but the mechanisms for such an effect are not defined.

The strongest evidence to date implicates elevated body mass index, high sodium intake, and elevated homocysteine levels as causal or facilitative in raising risk Mechanistic research reinforces the likelihood that the observed epidemiologic findings reflect causal relationships rather than chance associations or confounding.

For example, deleterious effects on myocardial function and metabolism, and even myocardial structure, have been observed under controlled conditions for animals and/or humans with varying degrees of obesity, insulin resistance, diabetes, and energy deficiency states such as starvation and anorexia nervosa.

Conversely, poor myocardial function can lead to distortions of energy balance as seen in cardiac cachexia or growth failure in children with congenital heart defects. Dietary lipid alterations may have direct myocardial effects, as seen in cholesterol cardiomyopathy of rabbits and long-chain fatty acid accumulation in humans.

Also, certain micronutrient imbalances, particularly of electrolyte minerals and trace elements, have been found to adversely affect myocardial function. For most vitamins, however, the role in cardiac function is not well defined, with the exception of thiamine.

Non-nutritive dietary compounds (such as coenzyme Q, taurine, and carnitine) that are found in food but also are ingested as dietary supplements have been studied with mixed results; the effects of these compounds on myocardial function are poorly understood. Nutrition in the management Compared with nutrition guidelines for other cardiovascular conditions, those for HF are minimal.

Patients and care providers alike seek well-integrated, robust nutritional guidance that accounts for specific therapeutic needs at various stages of disease, but also places them in a complete dietary context. Thus more information is needed in various HF patient populations regarding dietary macronutrient composition, overall dietary patterns (such as the DASH diet), and the appropriate usage of dietary supplements.

Information particularly is needed regarding appropriate weight loss modalities for HF patients who are obese or overweight. Also, given recent recommendations that most HF patients should engage in therapeutic exercise regimens, a better understanding is needed of the role of nutrition in improving exercise tolerance.

For example, glycogen-sparing diets may be able to enhance exercise capacity in HF, but have not been tested widely in different patient subgroups, such as those with concurrent diabetes. Advanced-stage HF patients treated with surgical approaches have unique nutritional problems that to date have been only minimally addressed.

Nutritional concerns among patients receiving left ventricular assist devices include impaired gastrointestinal function and high risk of nutrient depletion. Similarly, the optimal nutritional management of cardiac transplant patients is not well developed; problems include pre-transplant debilitation and post-transplant drug-nutrient interactions, obesity, hyperhomocysteinemia, and hyperlipidemia.

Better approaches are needed for characterizing nutritional status and managing nutritional support in such patients. Although dietary guidance often is a component of multi-disciplinary team management of HF patients, it usually is difficult to identify the specific benefits and cost effectiveness of nutrition services compared with other treatment modalities.

This is particularly important for HF patients, given that many hospitalizations are ascribed to deviations from diet and medication. Outpatients and hospitalized patients with HF need to be studied in terms of how to achieve good adherence and how to separate adherence vs. efficacy effects for dietary modifications.

Research also is needed on behavioral, psychosocial, family support, and other factors that affect the ability of HF patients to achieve adherence to dietary recommendations. Summary of research needs Hypothesis-testing research is needed to identify plausible biological mechanisms and to clarify the roles of specific foods, nutrients, and dietary patterns in the development and progression of HF.

Information is needed regarding applicability of veterinary, farm, and other animal models of nutrition-related HF to the human situation. Data are particularly needed in relation to the basic etiology and pathophysiology of cardiomyopathies and HF. There is a dearth of both observational and mechanistic studies related to nutrition in adult and pediatric HF patients at all stages of the disease.

Regardless of the original cause of the disease, patients with advanced cardiomyopathies or HF typically suffer from severe nutritional debilitation, but little guidance is available regarding optimal dietary management of such patients. Furthermore, rational dietary management of patients with relatively mild HF has not been fully explored, especially as an adjunct to pharmacologic therapy.

Appropriate investigations into delivery of nutrition-related health services also are needed. These would have real potential to generate data that can help in decisions related to design of health care systems, effectiveness of behavioral interventions, and cost effectiveness of various treatment paradigms.

Other topics of interest include studies of cardiac lipotoxicity (especially in association with obesity), cardiac cachexia and other problems of energy balance and metabolism, and nutrient metabolism in HF. There is a need for a more precise definition of cardiac cachexia (based on objective endpoints), as well as research to evaluate its effects on whole body metabolism and cardiac function, and on its treatment.

The role of dietary supplements in the management of HF patients needs to be better defined. Evaluations also are needed regarding the potential utility of dietary regimens and nutritional modifications for improving clinical outcomes in patients with HF, cardiomyopathy, heart transplants, or implantable devices.

A diverse array of investigator-initiated projects, solicited through this FOA, could effectively broaden the knowledge base on nutrition and HF. Most trials to date have been short-term and underpowered; the results have been hard to interpret, especially in the context of concurrent pharmacologic therapy; and the cardiac and nutritional endpoints often have been inadequate, preventing robust conclusions.

The greatest impact is expected to derive from small, focused, mechanistic studies that can provide a high-caliber evidence base for rational nutritional management of patients in various stages of HF. Such studies should be designed by multidisciplinary teams of investigators including cardiologists, nurses, and nutritionists.

Appropriate designs for studies in humans would address: statistical power; effect size of the intervention; appropriate homogeneity or heterogeneity of patient populations for testing the hypotheses of interest; potential confounding factors; time course of treatment; drop-out rates; dietary intake and nutritional status assessment; treatment compliance methodology; and intermediate measurements and surrogate endpoints relevant to HF research, including biological, clinical, and behavioral responses to specific interventions.

Epidemiology studies focused on the interaction between nutritional status and cardiac function/HF also are needed. Population studies also could be useful in assessing diet-disease risk relationships in population subsets such as patients with obesity, diabetes mellitus, and the metabolic syndrome.

Use of established cohorts or existing data sets could provide an efficient research approach, i.e., taking advantage of longitudinal or cross-sectional studies in which nutritional status, dietary, and cardiac function/structure endpoints were measured Existing data sets also could be a valuable resource for hypothesis-generating analyses and could provide descriptive data that might be the basis for power calculations for Suitable topics for research include, but are not limited to, the following: Studies to characterize novel and existing veterinary, agricultural, and laboratory small and large animal models of HF, across the range from fundamental mechanisms to whole organism function.

Studies using innovative genetic engineering approaches to evaluate the role of alterations in nutrient metabolism on cardiac function. Transcriptional profiling and proteomic approaches may be considered as appropriate. Studies in basic and clinical models to evaluate the potential association between myocardial lipid content, myocardial lipid metabolism, and cardiac dysfunction.

Research is encouraged that uses new approaches for accurate measurements of serum and myocardial lipid levels (such as in vivo scanning via MRI or PET and lipid fingerprinting of serum or tissue samples via Studies on the role of altered energy balance and other aspects of nutritional status in relation to the onset and long-term progression of HF in humans.

These could include studies of cachexic states; studies of patients with advanced disease treated with medical, surgical, or mechanical assistance approaches; and studies on the role of specific cytokines and other biological Studies on gastrointestinal function and nutrient malabsorption in HF.

Studies on the role of dietary modifications in the development or progression of HF, including alterations in proportions, composition, or intake levels of macronutrients, micronutrients, or other food constituents including non-nutritive dietary compounds. Studies to evaluate efficacy and effectiveness of various dietary regimens in the treatment of HF patients.

These could include studies examining effects of intake of sodium, potassium, and other nutrients; studies examining how the dietary treatment of hypertension (with or without concomitant pharmacologic treatment) affects risk or clinical status indices for diastolic and systolic HF; studies of specific dietary patterns; and studies assessing interactions of diet and exercise in HF patients.

Population-based studies on the interactions between diet, nutritional status and cardiac function, and assessing subgroups with various HF risk factor profiles, such as obesity and diabetes mellitus. Studies of cost-effectiveness and efficacy of nutrition-related health services, using study designs that can identify dietary protocol effects when many other services are provided simultaneously.

Studies on factors affecting adherence to dietary guidance, including best-practice approaches to implementation of dietary recommendations by patients and See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement. Section II. Award Information This funding opportunity will use the National Institutes of Health (NIH) Exploratory/Development Research Grant (R21) award mechanism.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. The R21 awards are to demonstrate feasibility and to obtain preliminary data testing innovative ideas that represent clear departure from ongoing research interests.

These grants are intended to: 1) provide initial support for new investigators; 2) allow exploration of possible innovative new directions for established investigators; and 3) stimulate investigators from other areas to lend their expertise to research within the scope of this solicitation. This funding opportunity uses just-in-time concepts.

It also uses the modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement: http://grants. nih. gov/grants/policy/policy.

htm#gps ). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium F&A costs), use the Modular Budget Component provided in the SF424 (R&R) Application Package and Instructions Guide (See specifically Section 5. 4).

The R21 grant support is for new projects only, and will not be renewed. Continuation of projects developed under this program will be through the regular research grant (R01) program. Two resubmissions (formerly called revisions) of a previously reviewed R21 grant application may be submitted as defined in the NIH policy at http://grants.

nih. gov/grants/policy/amendedapps. htm .

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Direct costs are limited to $275,000 over the two years of the R21 award, with no more than $200,000 in direct costs allowed in any single year. For example, you may request $100,000 in the first year and $175,000 in the second year.

Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this Program Announcement funding opportunity.

Facilities and administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004 . Section III. Eligibility Information 1.

A. Eligible Institutions You may submit (an) application(s) if your organization has any of the following characteristics: Public or private institutions, such as universities, colleges, hospitals, Units of State government Units of local government Eligible agencies of the Federal government Faith-based or community-based organizations Units of State Tribal government Units of Local Tribal government 1. B.

Eligible Individuals Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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 programs 2.

Cost Sharing or Matching This program does not require cost sharing as defined the current NIH Grants Policy Statement . 3. Other-Special Eligibility Criteria Section IV.

Application and Submission Registration and Instructions for Submission via Grants. gov To download an Application Package and Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www. grants.

gov/Apply/ and follow the directions provided on that Web site. A one-time registration is required for institutions/organizations at both: Grants. gov ( http://www.

grants. gov/GetStarted ) NIH eRA Commons ( http://era. nih.

gov/ElectronicReceipt/preparing. htm ) PD/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons . Several additional separate actions are required before an applicant institution/organization can submit an electronic application, 1) Organization/Institutional Registration in Grants.

gov/Get Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants. gov registration process. If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time.

A valid TIN or EIN is necessary for CCR registration. The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business Direct questions regarding Grants. gov registration to: Grants.

gov Customer Support Business Hours: M-F 7:00 a. m. - 9:00 p.

m. Eastern Time 2) Organization/Institutional Registration in the eRA Commons To find out if an organization is already Commons-registered, see the " List of Grantee Organizations Registered in NIH eRA Commons. Direct questions regarding the Commons registration Phone: 301-402-7469 or 866-504-9552 (Toll Free) Business hours M-F 7:00 a.

m. 8:00 p. m.

Eastern Time 3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users The individual designated as the PD/PI on the application must also be registered in the NIH eRA Commons. It is not necessary for PDs/PIs to register with Grants. gov. The PD/PI must hold a PD/PI account in the Commons and must be affiliated with the applicant organization.

This account cannot have any other role attached to it other than the PD/PI. This registration/affiliation must be done by the Signing Official (SO) or their designee who is already registered in the Commons. Both the PD/PI and SO need separate accounts in the NIH eRA Commons since both are required to verify the application.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization.

Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their institution is already registered in both Grants. gov and the Commons .

The NIH will accept electronic applications only from organizations that have completed all necessary registrations. 1. Request Application Information Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.

gov/Apply. Note: Only the forms package directly attached to a specific FOA can be used. Applicants will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the Attachment files may be useable for more than one FOA.

For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected] . Telecommunications for the hearing impaired: TTY 301-451-5936. 2.

Content and Form of Application Submission Prepare all applications using the SF424 (R&R) application forms and the SF424 (R&R) Application Guide ( MS The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH.

There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH ( e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID ). Agency-specific instructions for such fields are clearly identified in the Application Guide.

For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications . The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional.

The forms package associated with this FOA in Grants. gov/APPLY will include all applicable components, required and optional.

A completed application in response to this FOA will include the following components: SF424 (R&R) (Cover component) Research & Related Project/Performance Site Locations Research & Related Other Project Information Research & Related Senior/Key Person PHS398 Cover Page Supplement R&R Subaward Budget Attachment(s) Form Several special provisions apply to applications submitted by foreign organizations: Charge back of customs and import fees is not allowed.

Format: Every effort should be made to comply with the format specifications which are based upon a standard U.S. paper size of 8. 5 x 11 within each PDF. Funds for up to 8% administrative costs (excluding equipment) may be requested.

See NOT-OD-01-028 , Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards. Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.

2. , Administrative and National Security Requirements. Proposed research should provide a unique research opportunity not available in the United States.

3. Submission Dates and Times 3. A.

Submission, Review, and Opening Date: May 2, 2006 (Earliest date an application may be submitted to Grants. gov) Letter of Intent Receipt Date(s): Not applicable Application Submission Date(s): Standard dates apply. See http://grants1.

nih. gov/grants/funding/submissionschedule. htm Peer Review Date(s): Standard dates apply.

Please see http://grants. nih. gov/grants/funding/submissionschedule.

htm#reviewandaward Council Review Date(s): Standard dates apply. Please see http://grants. nih.

gov/grants/funding/submissionschedule. htm#reviewandaward Earliest Anticipated Start Date: Standard dates apply. Please see http://grants.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward A letter of intent is not required for the funding 3.

B. Sending an Application to the NIH To submit an application in response to this FOA, applicants should access this FOA via http://www. grants.

gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3. C. Application Processing Applications may be submitted to Grants.

gov on or after the opening date and must be submitted no later than 5:00 p. m. local time (of the applicant institution/organization) on the application submission date(s).

(See Section IV. 3. A.

for all dates.) If an application is not submitted by the submission date(s) and time, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be transferred from Grants.

gov to the NIH Electronic Research Administration process for validation. Both the PD/PI and the Signing Official for the organization must verify the submission via Commons within 2 business days of notification of the NIH validation. Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH.

Incomplete applications will not be reviewed. The 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. The NIH will not accept any application that is essentially the same as one already reviewed.

This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note such an application is considered a "resubmission" There will be an acknowledgement of receipt of applications from Grants. gov and the Commons .

Information related to the assignment of an application to the Scientific Review Group is also in This initiative is not subject to intergovernmental All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Pre-Award Costs are allowable.

A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH