INTERACTION OF GENES AND ENVIRONMENT IN SHAPING RISK FACTORS FOR HEART, LUNG, BLOOD, AND SLEEP DISORDERS Release Date: October 4, 2001 RFA: RFA-HL-02-010 (Notice of Limited Competition, see NOT-HL-06-123) National Heart, Lung, and Blood Institute (http://www.nhlbi.nih.gov) Letter of Intent Receipt Date: February 20, 2002 Application Receipt Date: March 22, 2002 PURPOSE Applications are being sought to identify novel genes which interact with specific environmental exposures to modify risk factors for heart, lung, blood, and sleep (HLBS) disorders. The genetic aspects of response to environmental change, and related biological mechanisms, will be studied using short term, focused interventions in families. The goal of this Request for Applications (RFA) is to identify subgroups based on genotype who are most likely to benefit from targeted environmental changes designed to reduce the development or progression of HLBS diseases. HEALTHY PEOPLE 2010 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Interaction of Genes and Environment in Shaping Risk Factors for Heart, Lung, and Blood Diseases, is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/ ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non- profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) cooperative agreement (U01) grant mechanism. Under the cooperative agreement, the NIH assists, supports and/or stimulates, and is substantially involved with recipients in conducting the study by facilitating performance of the effort in a partner role. Individually funded grants under this RFA are requested to collaborate in areas which have broad applicability across all funded studies, such as recruitment, informed consent, adherence, data analysis methodology and data sharing policies. Details of responsibilities, relationships, and governance of research funded through this cooperative agreement are discussed under SPECIAL REQUIREMENTS. The total project period for an application submitted in response to this RFA may not exceed four years. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. The anticipated award date is September 30, 2002. FUNDS AVAILABLE The NHLBI intends to commit approximately $9,000,000 in FY 2002 to fund 3 to 5 new grants in response to this RFA. Up to $36,000,000 (total cost) over the entire project period is available to support this initiative. Because the nature and scope of the research proposed may vary, it is anticipated that the size of each award will also vary. Although the financial plans of the NHLBI provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. At this time, there is no plan to reissue this RFA. RESEARCH OBJECTIVES Background Complex diseases, such as coronary heart disease, asthma, anemias, sleep disordered breathing, and their antecedent risk factors (e.g., dyslipidemia, bronchial reactivity, iron binding capacity, and obesity), are by definition influenced by multiple genes interacting with each other and with the environment. Deciphering the underlying genetics of such diseases and their risk factors can be extremely difficult when these complex interactions are not adequately assessed and not understood. To date the search for new genes affecting HLBS disease risk has produced many inconsistent results. One reason is that the influence of environmental factors on measured phenotypes can vary by genotype. Blood pressure response to a low sodium diet, for example, has been shown to vary by polymorphisms of renin-angiotensin system genes. In addition, LDL-cholesterol response to the National Cholesterol Education Program (NCEP) Step II diet has been shown to differ by variants in the ApoA1 gene. Failure to consider such interactions often results in the inability to detect or accurately quantify the underlying genetic contribution to phenotypic variability. Elucidation of the genetic architecture of complex HLBS diseases and their risk factors will require meticulous assessment of environmental exposures and consideration of their influences on gene expression. However, even well defined environmental exposures, such as smoking, have been difficult to accurately measure in observational studies. It is possible that substantial short-term modifications of the environment, such as dramatic changes in dietary composition or exposure to bronchoconstricting or dilating agents, may be needed to unmask variation in response to environmental factors. Such responses, and their relationships to genotypic variation, may not be detectable given the range of environmental variation normally seen in observational studies. Identifying genes that interact significantly with modifiable environmental factors will have significant public health and clinical implications. Genotypic characterization of individuals who respond favorably to a short- term intervention may enable targeted interventions to reduce risk factors and may help to identify the most effective treatments in clinical practice. For example, the identification of genotypes that predispose individuals to thrombosis (such as Factor V Leiden mutations) in physically inactive individuals might lead to the recommendation for individuals with that genotype to maintain a strict exercise program. From a public health standpoint, individuals with modifiable genetic risk of disease could be identified prior to disease development. Effective, appropriate interventions tailored to the unique genotypic characteristics of an individual could then be initiated to reduce the likelihood of developing the disease or modify its outcome. Identification of environmental modifiers of gene expression will permit direct application of human genome sequence information to improve the health of the public in the future. Advances in this area could significantly enhance the effectiveness of clinical care and particularly of risk factor modification. Research Plan This initiative will support several studies to examine genetic influences on response to short term, focused interventions or environmental modifications with, prior evidence of efficacy, in families at risk of HLBS diseases. Studies of genetic variation are increasingly being used in clinical trials and intervention studies to evaluate the impact of polymorphisms in known candidate genes on the response to intervention in unrelated individuals. However, intervention methodologies have not been widely applied to families. The primary advantage of studying families is the ability to localize novel genes related to response to environmental change, through genetic linkage methodologies, as well as testing candidate genes. In addition, identification of novel genes related to response to environmental change will be facilitated by studying them on a more homogeneous genetic and environmental background than is typical of clinical or population-based studies of individuals. Such "background" variation is reduced among families and in more discrete racial/ethnic groups. In addition, interventions adopted by family units may be more successful than when applied to individuals. For example, interventions involving allergen reduction, changes in diet, exercise, smoking cessation, or reduction in chronic sleep deprivation may have higher adherence when there is support from other family members who are also adopting healthy habits or changing the home environment. Examples of proposals responsive to this RFA include, but are not limited to: A) A proposal designed to localize novel genes contributing to change in lipid profile after exposure to NCEP Step II diet. B) A proposal to localize genes influencing change in blood pressure in response to short term mental stress. C) A proposal to search for genes influencing change in hemostasis in response to antithrombotic drugs, such as aspirin. D) A proposal to localize novel genes contributing to change in lung function in response to decreased exposure to allergens and/or viral triggers of asthma. E) A proposal to search for genes influencing weight loss and change in sleep disordered breathing (SDB) in response to exercise. 1. Recruitment and Ascertainment of families The group of families adopting a given intervention will ideally be ascertained from a single site and will all belong to the same racial/ethnic group to minimize environmental and genetic heterogeneity. However, recruitment of families may occur at several different geographic sites. Applicants proposing recruitment over several geographic sites must demonstrate adequate quality control and oversight of recruitment, examination and intervention phases of the study. Furthermore, the applicant may wish to subcontract with field centers or make collaborative agreements with field centers for recruitment, examination and intervention phases to ensure that all activities are encompassed within a single grant application. If appropriate for the intervention and scientific hypotheses, families recruited as part of a pre-existing study may be enrolled in the current intervention. The application must demonstrate the appropriateness of the existing families for the protocol and provide assurance that all additional recruitment will occur in a consistent manner. For all proposed study sites, applicants must demonstrate the ability to recruit families, implement examination and intervention procedures, and provide evidence of ability to maintain high rates of followup throughout the intervention. Families may be ascertained based on an index member whose risk profile is appropriate for the short-term intervention. For example, in a protocol designed to raise HDL-C in response to an intensive exercise regimen, the index family member would have a low to moderate HDL-C level. If a random ascertainment strategy is adopted, the applicant must justify the appropriateness of the sample in terms of variability of response to intervention and power to detect gene by environment interactions. Adequate representation of racial and ethnic minorities will be required for the program as a whole. 2. Sample Size and Power Calculations To ensure acceptable statistical power, the recruitment design should include an adequate number of families of sufficient size to detect gene - environment interactions. Families may be randomized into intervention and control groups. In addition, the intervention chosen must be of proven efficacy, and of sufficient magnitude and duration to produce a response in the quantitative risk factor of interest. Applicants must justify family size, ascertainment strategies, intervention protocol and their choice with respect to randomization. For example, if moderate to large nuclear families (family size of 6 or more) are ascertained, the total sample size for interventions in which a control group is required is estimated to be approximately 2,500 individuals (420 families randomized equally to intervention and control groups). 3. Clinical Examinations and Intervention Baseline measurements of multiple risk factors, medical and sleep history, environment, and lifestyle, as appropriate, will be made prior to intervention. Applicants should carefully assess risk factors and environmental exposures which may impact the outcome of the intervention. Although all such confounders can not be completely assessed, the applicant should demonstrate that the baseline risk profile and environmental exposures are measured to the best of their ability and are considered in the analysis of the resulting data. Interventions will be of short duration, and some could be given as a single challenge, the exact length will depend on the type of intervention. Multiple short-term interventions might be undertaken sequentially in identified families. The type of intervention should be one that is known to produce measurable outcomes over a short period of time and that is feasible to implement in families. Examples include exercise training and/or calorie restriction for changes in body composition or sleep disordered breathing, decreased salt intake for changes in blood pressure, or aspirin for changes in coagulation parameters. Interventions could also take the form of an environmental perturbation or challenge, such as a high-fat meal, mental stress, cold pressor test, or exposure to a bronchoconstricting or dilating agent. Outcome variables should be quantitative risk factors for HLBS diseases, such as serum LDL-C or blood pressure, or disease manifestations such as degree of bronchodilation. Families will be reassessed for the same phenotypes after the intervention as in the baseline exam. Applicants must demonstrate that the proposed intervention has a proven impact on the phenotypes of interest and is feasible to implement in families, including those members not affected by the disorder. Studies implementing interventions that impact multiple quantitative outcomes are encouraged. Applicants who choose to implement multiple interventions in the same families must demonstrate that the initial interventions will not impact the outcome of subsequent interventions. 4. Data Analyses Novel approaches to the identification of genes that influence response to specific interventions is encouraged. Data analyses can include, but are not restricted to gene localization using linkage based analyses, combined linkage and association analysis, polymorphism testing in candidate genes by family based association analyses and haplotype-based analyses. Applicants are encouraged to make full use of the longitudinal nature of the data and the family structure in their analytic plan. A program-wide committee will be formed to discuss and promote new analytic methods for the analysis of gene- environment interaction. Applications are limited to four years and each should consist of a single application demonstrating the capacity for recruiting families, performing clinical examinations, delivering the intervention(s), assessing the appropriate response variables, conducting the laboratory work, managing data and conducting the analysis. Subcontracts or collaborative agreements may be used for specialized services or recruitment off site. Each application must specify the research questions to be addressed, the interventions to be delivered, power calculations and the proposed genetic and statistical analyses to be conducted. The cost of recruiting families may be offset by utilizing existing cohort studies. This initiative proposes to fund 3-5 such applications, aiming for programmatic balance across cardiovascular and/or sleep disorders, blood disease, and lung disease. SPECIAL REQUIREMENTS To be responsive investigators must propose to localize and/or identify genes contributing to response to specific environmental perturbations using short term interventions in families. Applicants must justify the proposed study design and sample size and provide power calculations. Program Organization 1. Administrative Coordinating Center The Administrative Coordinating Center functions will be performed by one of the study centers. The Administrative Coordinating Center will coordinate activities across the three to five studies funded in this RFA and assist in the organization and monitoring of committees and issues that have broad applicability across all funded studies, such as recruitment, informed consent, analysis methodology and data sharing. The Administrative Coordinating Center will also be responsible for monitoring membership of Program wide committees, tracking and scheduling of committee meetings and conference calls, and planning DSMB meetings. Applicants who are interested in fulfilling the role of the Administrative Coordinating Center for this RFA should include a section in their application describing their anticipated activities as the Administrative Coordinating Center and a separate budget for these activities in their applications. Applicants should include costs of monthly Steering Committee conference calls and travel funds for 8-10 DSMB members to attend meetings in Bethesda twice a year. Travel funds should also be included for the Steering Committee Chairman to attend two annual meetings in Bethesda. 2. Internal Governance of Each Study Each study will establish an internal organization by which they govern and oversee various components of the study. This organization will oversee and approve all protocols and procedures involved in the performance of the research and publication of findings. Applicants should include a description of the organization, as well as a budget to cover monthly meetings and/or conference calls. 3. Steering Committee The Steering Committee, comprised of each PI, a Co-PI from each study, and NHLBI Scientific staff, will identify issues that have broad applicability across the program. Initial recommendations regarding program level organization, consistency across studies in areas which would benefit from a coordinated research effort will be made by the Steering Committee. Such recommendations might involve areas such as standardized aspects of informed consent, data analysis techniques, data sharing and publications policy, recruitment, protocol development and adherence. Applicants should budget for meetings to be held twice a year in Bethesda. 4. Data Safety and Monitoring Board An independent program - wide Data Safety and Monitoring Board will be appointed by the Director of NHLBI. Descriptions of the board membership, scheduling, responsibilities and authority are listed under "TERMS AND CONDITIONS OF AWARD". Each study should budget for the PI and one Co-PI to travel to Bethesda twice a year to attend DSMB meetings. Data Sharing Studies within the Program are expected to utilize a collaborative approach to data analysis and interpretation. It is expected that a program-wide Analysis Committee, consisting of at least one member from each study and at least one NHLBI Scientist, will explore methods for analyzing family based intervention data. The activities of the Analysis Committee will at the minimum involve identification of the best existing statistical methods for analysis and if needed, development of new statistical methodologies. If appropriate, the activities of the Analysis Committee may involve joint analysis and interpretation of unpublished results. Applicants should budget for an annual meeting in Bethesda. Each study must provide a policy for sharing data collected with funds from this RFA with the scientific community. Applicants should outline how collaboration with the scientific community will be facilitated, for example review policies for ancillary study or collaborative proposals that may arise from the scientific community, description of publicly available information and methods of dissemination. The adequacy of the applicant=s plan to share data with the outside community will be evaluated in the review of the application. Applicants should plan to provide a limited access data set to the NHLBI within three years following the close of this grant period (end of the fiscal year 2009). Limited access data refers to trial or study data, with certain deletions and recoding (to ensure participants= privacy and confidentiality), that are released to requesting institutions and investigators for specific purposes and with certain restrictions and conditions. Limited access data will be made available to the public in accordance with the NHLBI Policy for Distribution of Data (http://www.nhlbi.nih.gov/resources/deca/policy.htm). In brief, the limited access data sets are stripped of all obvious and inadvertent personal identifiers and the data may be grouped or modified slightly to prevent identification of individuals in the study. The limited access data would include baseline measures and outcome data, pedigrees and genotypes. Furthermore, stored samples should be made available upon request. Individuals requesting data must adhere to the requirements of a Distribution Agreement and submit an approval from their Institutional Review Board (IRB). TERMS AND CONDITIONS OF AWARD The cooperative agreement is an award instrument establishing an assistance relationship between NHLBI and a recipient, in which substantial NHLBI scientific and/or programmatic involvement with the recipient is anticipated during the performance of the activity. The NHLBI purpose is to support or stimulate the activity in a "partner" role, but avoiding a dominant role, direction or prime responsibility. The terms and conditions outlined below elaborate on these actions and responsibilities, and the awardee agrees to these collaborative actions with the NHLBI Project Scientist toward achieving the project objectives. It is expected that these terms and conditions will enhance the relationship between the NHLBI staff and the principal investigator(s), and will facilitate successful conduct and completion of the study. These agreements will be in addition to, and not in lieu of, the relevant NIH procedures for grants administration. The terms will be as follows: 1. The awardee(s) will have lead responsibilities in all aspects of the study, including study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee. 2. The NHLBI Project Scientist will serve on the Steering Committee, NHLBI scientist (s) may serve on other study committees, when appropriate. The NHLBI Project Scientist (and other cited NHLBI scientists) may work with awardees on issues before the Steering Committee, and as appropriate, other committees, for example: recruitment, intervention, quality control, data analysis and publication, and preparation and development of solutions to major problems such as insufficient participant enrollment. 3. Awardee(s) agree to governance of the program through a Steering Committee. Steering Committee voting membership shall consist of the principal investigators (i.e., the cooperative agreement awardees) and the NHLBI Project Scientist. Monthly meetings of the Steering Committee will ordinarily be held by telephone conference call. In person meetings should be held biannually in Bethesda. 4. A Program - wide Data Safety and Monitoring Board (DSMB), consisting of 8- 10 members, will be appointed by the Director, NHLBI to provide overall monitoring of interim data and safety issues for all studies awarded through this RFA. Biannual meetings of the Data Safety and Monitoring Board will ordinarily be held in Bethesda. An NHLBI Scientist will serve as Executive Secretary to the DSMB. 5. Awardees will retain custody of and have primary rights to their data developed under these awards, subject to government rights of access consistent with current HHS, PHS and NIH policies. The collaborative protocol and governance policies will call for procedures for data analysis, reporting and publication, and procedures to protect and ensure the privacy of individual medical records and genetic data. The NHLBI Project Scientist, on behalf of the NHLBI, will have the same access, privileges and responsibilities regarding the data as the other members of the Steering Committee. 6. Support or other involvement of industry or other third party in the study C- e.g., participation by the third party, involvement of study resources or citing the name of the study or NHLBI support, or special access to study results, data or resources B- may be advantageous or appropriate. However, except for licensing of patents or copyrights, support or involvement of a third party will occur only following notification of and concurrence by NHLBI. 7. Awardees are encouraged to publish and to publicly disseminate results, data and other products of the study, concordant with the study protocol and governance, and the approved plan for making data and materials available to the scientific community and NHLBI. However, during or within three years beyond the end date of the project period of NHLBI support, unpublished data, unpublished results, data sets not previously released, or other study materials or products are to be made available to any third party only with the approval of the Steering Committee and in accordance with paragraph 6. 8. The NHLBI reserves the right to terminate or curtail the study in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol, (b) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breech of protocol, (c) substantive changes in the protocol with which NHLBI can not concur, (d) human subject ethical issues that may dictate a premature termination. 9. Any disagreement that may arise in scientific/programmatic matters (within the scope of the award), between recipients and the NHLBI may be brought to arbitration. An arbitration panel will be composed of three membersBone selected by the Steering Committee (with the NHLBI member not voting), or by the awardee in the event of an individual disagreement, a second member selected by NHLBI, and a third selected by the two prior members. This special arbitration procedure in no way affects the awardee=s right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, subpart D and HHS regulation at 45 CFR part 16, or the rights of NHLBI under applicable statues, regulations and terms of the award. 10. These special terms of award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74, and other HHS, PHS and NIH grant administration policy statements. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a complete copy of the updated Guidelines are available at https://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The revisions relate to NIH defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable, and b) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the Inclusion of Children as Participants in Research Involving Human Subjects that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: https://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators also may obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. This policy announcement is found in the NIH Guide for Grants and Contracts Announcement dated June 5, 2000, at the following website: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. URLS IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at: https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm Applicants may wish to place data collected under this RFA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should address in their applications how they will structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. The letter of intent is to be sent to Dr. Deborah Beebe listed under Inquiries no later than February 20, 2002. APPLICATION PROCEDURES The PHS 398 research grant application instructions and forms (rev. 5/2001) at https://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in applying for these grants. This version of the PHS 398 is available in an interactive, searchable PDF format. Beginning January 10, 2002, the NIH will return applications that are not submitted on the 5/2001 version. For further assistance contact GrantsInfo, Telephone 301/710-0267, Email: GrantsInfo@nih.gov. The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: https://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application as well as all five collated sets of Appendix material must be sent to Dr. Deborah Beebe at the address listed under inquiries. Applications must be received by the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an Introduction addressing the previous critique. Principal investigators should not send supplementary material without first contacting the Scientific Review Administrator (SRA). The SRA will be identified in the letter sent to you indicating that your application has been received. If you have not yet received such a letter within three weeks after submitting the application, contact Dr. Deborah Beebe at the address listed under inquiries. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NHLBI. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NHLBI in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed, assigned a priority score, and receive a second level review by the National Heart, Lung, and Blood Advisory Council. Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. (1) Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation: Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research. o The adequacy of the proposed protection for humans, animals or the environment, to the extent they may be adversely affected by the project proposed in the application. o The adequacy of the proposed plan to share data. Schedule Letter of Intent Receipt Date: February 20, 2002 Application Receipt Date: March 22, 2002 Peer Review Date: June 2002 Council Review: September 2002 Earliest Anticipated Start Date: September 30, 2002 AWARD CRITERIA Award criteria that will be used to make award decisions include: o scientific merit (as determined by peer review) o availability of funds o programmatic priorities. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or answer questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Cashell E. Jaquish, Ph.D. Division of Epidemiology and Clinical Applications National Heart, Lung and Blood Institute Rockledge II, Room 8170 MSC 7934 6701 Rockledge Drive Bethesda, MD 20892-7934 Telephone: (301) 435-0447 FAX: (301) 480-1455 Email: jaquishc@nhlbi.nih.gov Mariana Gerschenson, Ph.D. Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute Rockledge II, Room 9180 MSC 7940 6701 Rockledge Drive Bethesda, MD 20892-7940 Phone: 301-435-0515 FAX: 301-480-1336 Email: gerschem@nhlbi.nih.gov Charles Peterson, M.D. Division of Blood Diseases Research National Heart, Lung, and Blood Institute Rockledge II, Room 10158 MSC 7950 6701 Rockledge Drive Bethesda, MD 20892-7950 Phone: 301-435-0050 FAX: 301-480-0868 Email: petersoc@nhlbi.nih.gov Susan Banks-Schlegel, Ph.D. Division of Lung Diseases National Heart, Lung, and Blood Institute Rockledge II, Room 10018 MSC 7952 6701 Rockledge Drive Bethesda, MD 20892-7952 Phone: 301-435-0202 FAX: 301-480-3557 Email: schleges@nhlbi.nih.gov Carl E. Hunt, M.D. National Center on Sleep Disorders Research National Heart, Lung, and Blood Institute Rockledge II, Suite 10138 MSC 6701 Rockledge Drive Bethesda, MD 20892- Phone: (301) 443-0199 Fax: (301) 480-3557 E-mail: huntc@nhlbi.nih.gov Direct inquiries regarding review issues and send letters of intent to: Deborah Beebe, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7178, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0270 FAX: (301) 480-3541 Email: beebed@nhlbi.nih.gov Direct inquiries regarding fiscal matters to: Leslie Boggs Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7142,MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0177 FAX: (301) 480-3310 Email: boggsl@nhlbi.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.839. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.
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NIH Funding Opportunities and Notices
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
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