DATA COORDINATING CENTER FOR THE SLEEP HEART HEALTH STUDY Release Date: February 11, 1999 RFA: HL-99-014 P.T. National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: March 1, 1999 Application Receipt Date: March 25, 1999 PURPOSE The purpose of this initiative is to solicit applications for a new Data Coordinating Center (DCC) for the Sleep Heart Health Study (SHHS). The SHHS is a multi-center, epidemiological investigation to assess sleep apnea as an independent or contributing risk factor for the development of cardiovascular and cerebrovascular disease. The SHHS utilizes existing cardiovascular cohorts, to examine whether sleep-disordered breathing (SDB) is associated with an increased risk of incident coronary heart disease events, incident stroke, increase in blood pressure and increased risk of all cause mortality. The SHHS has completed home sleep studies on over 6,400 subjects and has begun to analyze these data in relationship to existing cardiovascular outcomes. The next competitive phase of the program will continue to address the primary hypothesis through repeat sleep studies and follow-up. A single DCC will support protocol development, sample size calculations, common questionnaires, complete data analysis, data management, standardization of procedures, quality control, development of analytical models, utilization of extensive longitudinal data from cardiovascular epidemiological cohorts, and overall study coordination required by the multi- center research program under the cooperative agreement mechanism (U01). This announcement is to invite applications for a DCC from all potential applicants. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Data Coordinating Center for the Sleep Heart Health Study, is related to the priority areas of heart disease and stroke, clinical prevention services, diabetes and chronic disabling diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). It may also be found at http://www.crisny.org/health/us/health7.html. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic organizations, for-profit and non-profit, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Foreign organizations may not apply as the coordinating center for this program should reside within the U.S. in order to provide the resources to the U.S. clinical centers as well as ready access and familiarity with existing longitudinal data from other cardiovascular disease populations and cohorts. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Applicant organizations should have experience functioning as a statistical coordinating center for multi-site clinical research of a medical and/or behavioral nature. The principal investigator of an existing SHHS clinical center may not apply for the DCC to ensure that data analysis is done independently of data acquisition. However, individuals other than the principal investigator of the SHHS center at the same institution may apply for the DCC award. Data coordinating centers currently involved with epidemiology cohort studies are eligible. MECHANISM OF SUPPORT This RFA will use the cooperative agreement (U01) administrative and funding mechanism of support. Under the cooperative agreement, the NIH assists, supports, and/or stimulates, and is substantially involved with recipients in conducting a study by facilitating performance of the effort in a "partner" role. Details of the responsibilities, relationships, and governance of a study funded under a cooperative agreement are discussed later in this document under the section entitled RESEARCH OBJECTIVES. The total project period for applications submitted in response to this RFA may not exceed 5 years. This RFA is a one-time solicitation. The anticipated start date is September 30, 1999. FUNDS AVAILABLE It is anticipated that one award for a DCC will be made. Applicants may request a project period of up to 5 years and a budget for total costs of $700,000 in the first year. Any sub-contract costs and F&A costs should be included in this total amount. Facilities and administrative costs (formally indirect costs) will be awarded based on the grantee's negotiated rate. Future year annual increments in direct costs are not to exceed three percent. 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 applications of outstanding scientific and technical merit. Designated funding levels are subject to change at any time prior to final award, due to unforeseen budgetary, administrative, or scientific developments. Funding of the DCC will be contingent upon successful competitive renewal and funding of the SHHS clinical centers. RESEARCH OBJECTIVES A. Background There has been accumulating evidence over the past several years that sleep apnea leads to alterations in the cardiovascular system, which may predispose to morbid cardiovascular events and even sudden death. Results from population-based studies suggest that sleep-disordered breathing, ranging from mild to moderate severity, is an independent risk factor for hypertension and elevated blood pressure during both wakefulness and sleep. Furthermore, the relative risks of ischemic heart disease, myocardial infarctions and cerebrovascular accidents range from 1.5 to 4 in snorers as compared to non- snorers. Hypertension is common in patients with sleep apnea; other studies suggest that up to 40% of hypertensive patients may have significant sleep apnea. Improvement in hypertension control has been reported to occur in patients with both conditions following treatment of their apnea. Cardiovascular mortality may be significantly higher among untreated or conservatively treated patients with sleep apnea compared to aggressively treated patients. Sleep apnea may be an independent cardiovascular disease risk factor, a concomitant of established cardiovascular or cerebrovascular diseases or other risk factors (such as obesity or hypertension), but this remains to be determined. Similarly, little is known regarding potential interactions between sleep apnea and other risk factors, or whether specific population subgroups may be particularly susceptible to adverse cardiovascular and cerebrovascular consequences potentially associated with sleep apnea. The profound physiological derangements (hypoxemia, severe hypertension, tachycardia, fragmentation of sleep, arrhythmias) that often occur in association with sleep-disordered breathing provide biologically plausible explanations for associations between sleep apnea and cardiovascular morbidity. Although the limited epidemiological studies are suggestive of sleep apnea as a potential risk factor for systemic hypertension, a direct etiologic link between the two disorders and the specific physiologic mechanisms has been difficult to demonstrate. The combination of the epidemiological evidence demonstrating more night time cardiovascular abnormal events in persons with mild asymptomatic sleep apnea, coupled with animal model data, implies that there is a causal relationship between sleep apnea and cardiovascular disease. The high prevalence of both disorders in the population suggest that sleep apnea may be a potential modifiable risk factor for the prevention of heart disease and stroke. Identification of factors that predispose to increased risk for sleep apnea is important for public health policy. It will allow specific high risk populations to be targeted and provide an improved understanding of disease pathogenesis that may include interactions among a number of risk factors. The SHHS has established a highly interactive, coordinated group of clinical centers working under a common protocol to investigate these relationships. The initial study was established in 1994 with six clinical centers and one data coordinating center. During the initial 5 year period, home sleep studies have been conducted on more than 6,400 subjects. Data analysis and publication of the initial cross sectional findings are underway. The clinical centers have submitted competitive renewal applications to continue to test the primary hypothesis through repeat sleep studies and longitudinal follow up. B. Objectives and Scope The overall objective of the SHHS is to utilize existing, well characterized, population-based epidemiologic cohorts (parent studies) to determine the degree to which sleep apnea is an independent or contributing risk factor for the development of cardiovascular and cerebrovascular disease. It is also aimed at examining possible associations between sleep apnea, hypertension and stroke within different age, gender and racial/ethnic groups. This program has five specific aims. o Determine the risk of cardiovascular disease (CVD) associated with sleep apnea and other sleep related breathing disorders independent of other cardiovascular disease risk factors; o Assess potential interactions between sleep apnea and other vascular disease risk factors, particularly obesity and hypertension, in relation to CVD risk; o Examine the contribution of sleep apnea to the development of other CVD risk factors, particularly hypertension; o Identify population subgroups at greatest risk for adverse clinical outcomes from sleep apnea including those defined by age, gender and race; o Estimate the extent of medical care utilization, health care costs, and measures of quality of life associated with sleep apnea. These aims are designed to test four primary hypotheses developed by the SHHS investigators. o Sleep-disordered breathing is associated with an increased risk of incident coronary heart disease events. o Sleep-disordered breathing is associated with an increased risk of incident stroke. o Sleep-disordered breathing is associated longitudinally with increased blood pressure. o Sleep-disordered breathing is associated with increased risk of all-cause mortality. Although these are the primary hypotheses to be tested by the SHHS, others may be appropriate and the program is not restricted to the primary hypotheses listed above. A number of secondary hypotheses will be tested either on the entire cohort or subsets where appropriate covariate data exist. Information about protocols, hypotheses, ancillary and substudies, the SHHS Manual of Operations, the Reading Center Manual of Operations and the characteristics of study datasets can be obtained by contacting the scientific project officer listed under INQUIRIES. Some of this information is also available from the SHHS home page at: http://140.142.220.29/shhs/ SHHS Design The SHHS cohort was established by recruiting a sample of snorers and non- snorers from existing NHLBI-supported cohorts, including the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Heart Study (CHS), the Strong Heart Study (SHS), the Framingham Heart Study (FHS), the Tucson Epidemiologic Study of Obstructive Airways Disease, the Tucson Health and Environment Cohort, and three New York cohorts. In total, 6,400 subjects from 10 clinical sites and six administrative entities were recruited and completed a baseline sleep study. Data previously collected by the existing parent studies provided baseline (prior to the sleep study) information on hypertension, obesity, and other cardiovascular risk factors, and prevalent cardio/cerebrovascular disease. Polysomnography variables, collected by unattended multi-channel sleep studies, were obtained on cohort members following a standardized home visit protocol. A reading center, located at Case Western University was responsible for evaluation and quality grading of all polysomnography (PSG) data. Key data not collected for any given cohort, and data that could vary over time and influence interpretation of the sleep study or the relationship of the sleep variables with cardiovascular outcomes, also were directly measured or assessed during the home visit. The comparability between cohorts and sites of all key predictor and outcome data obtained from the parent studies was assessed. Follow-up data, including cardiovascular outcomes, were assessed in 18 to 36 month follow-up visits and telephone calls. Sub-studies were performed to assess scoring reliability, night to night variability of sleep studies, and comparability of laboratory and home-based sleep studies; the relationship of measured urinary catecholamines and SDB; and the relationship of SDB with neuropsychological functions. A large amount of covariate and outcome data has been collected from the parent cohorts. The proposed plans for continuation of SHHS call for collection of additional follow-up data to provide statistical power to assess the relationship of SDB with incident cardiovascular diseases. Other objectives likely will include: follow-up sleep studies to describe the change in SDB over time, and the impact of change in SDB indices with incident cardiovascular disease; functional outcomes (sleepiness, general health and functional status); and assessment of pathophysiological processes that may mediate cardiovascular diseases associated with SDB, and identification of interactions between SDB and other risk factors in the development of CVD. Morbid outcomes may be defined with the use of several measures, such as evidence of left ventricular dysfunction, sustained hypertension, atherosclerosis, cognitive impairment, hospital admissions for treatment of ischemic heart disease, health care expenditures associated with CVD and cerebrovascular disease, measures of functional status, quality of life, and death. Data Coordinating Center Design Applications should present a plan for a data coordinating center which includes approaches to the following activities and any others that would complement the functions outlined below. All plans should be compatible with procedures and requirements outlined in the SHHS Manual of Operations. It is anticipated that the plans of the successful DCC application will be submitted to the SHHS steering committee for further consideration and that final plans will be developed once the cooperative agreement has been awarded. A decision to fund a particular DCC application will not commit the SHHS steering committee to conduct the specific plans outlined in that application. For any activities to be conducted through subcontracts, applicants should develop and describe such operational factors as access to subjects, organization of the facility, means of assuring quality control, data entry, plans for coordination, and a process for filing human subject assurances. 1) Data Coordination a. Assume responsibility for the common database currently in existence to which all SHHS clinical centers contribute demographic, clinical, physiological, and pathological information about subjects in a standard format. The DCC is expected to provide leadership with respect to the orderly, timely, accurate accumulation and transmission of these data. Plans should include, but are not limited to, designing efficient systems for collecting and managing data, operational and management structures providing lines of responsibility and staffing for DCC functions across the life of the study; tracking and implementation of established study protocols and proposed analyses as described in the SHHS Manual of Operations; calculations for operational costs for all DCC functions; data acquisition, transfer, and management; the tabulation of survey instruments such as the Sleep Habits Questionnaire; printing and distribution of study protocols; report preparation; data archiving and backups of study data; maintain and expand SHHS web site; and duplication for storage at each clinical site. b. Using the data collected before the sleep study will require state-of-the- art longitudinal data analysis techniques. Approaches will be needed to use previously collected information. For example, modeling approaches will be needed to address the natural history of sleep-disordered breathing and its relationship with CVD risk. Applicants should be familiar with approaches for analysis of longitudinal data on blood pressure and time-varying predictors of CVD occurrence. Also, expansion of the common database to use existing data from the parent cohorts or collect cohort-specific data for comparisons that could be important to the study objectives such as the identification of prevalent cardiovascular disease and hypertension, lung function abnormalities (spirometry), and potential confounders such as body weight, smoking, and medications. Expansion will entail surveying parent cohort database structures; proposing ways to facilitate and integrate common variables and index non-conforming variables in the common database; time lines for completion of data migration; establish a database to collect and maintain parent cohort endpoint data and develop procedures for adjudication of the major study endpoints; and working with the sleep reading center for quality control. Provide leadership in addressing complex analysis issues, including data comparability issues, and interactions between sleep variables and other risk factors in relation to CVD risk; longitudinal data analysis and model development; innovative uses of the extensive CVD data collected from various population-based studies; oversee quality control activities. c. Plans and time line for the orderly transfer of SHHS data, documentation and programs from the incumbent DCC to the new DCC. Also, transfer of data to the NHLBI or another DCC at the end of the funding period. d. Plans to facilitate DCC participation in further data sharing efforts and studies using the databases. e. Training programs to educate DCC and SHHS staff about operating procedures with the goal of maximizing efficiency and accuracy in data operations. Establish quality control procedures including those for field center technicians for protocol adherence and home data collection. f. Procedures to work with the Reading Center to assure data quality and confidentiality of subjects. g. Procedures to disseminate data available in the DCC. h. Provide administrative support and participate in steering committee and subcommittee activities, including maintaining a database to track proposed and active manuscripts and interact with parent studies for clearance of all publications. i. Provide statistical advice and consultation on study design to investigators involved in studies approved by the SHHS Steering Committee and to encourage maximum use of data collected by the DCC. Assume primary responsibility for all statistical analysis. 2) Interactions with Sleep Reading Center Coordination of all data collection and analyses integrally involve PSG data uniquely designed for SHHS. It is anticipated that because of the complexity of the PSG data, and procedures already developed for managing these data, and to minimize the need for the new DCC to learn all the details of the PSG data, the Reading Center will assume responsibility for the preliminary analysis, clean-up, storage, archiving and reporting polysomnography data for the main purpose of processing, tracking performance and PSG quality control. The Reading Center will transfer data to the DCC, which will be responsible for overall quality control procedures and primary statistical analyses as well as general study logistics (organization of subcommittees, meeting logistics, generation of forms, collation of data from parent cohorts, and collection of data from survey instruments/questionnaires). 3) Coordination of meetings and reports a. Administratively support the SHHS steering committee, which includes the principal investigator of the DCC; the principal investigator of individual clinical centers and the reading center; specialized external consultants; the Data Safety and Monitoring Board (DSMB), and NHLBI staff. The steering committee must be kept informed and approve of any changes in policy. b. Organize and provide administrative support including preparing the minutes for meetings and teleconferences called for by the SHHS steering committee or its sub committees to monitor operations; approve changes in procedures; and facilitate other coordination activities. c. Prepare regular reports as defined in SHHS Manual of Operations, or requested by the SHHS steering committee, sub committees, and NHLBI staff. SPECIAL REQUIREMENTS Terms and Conditions of Award The cooperative agreement is an award instrument establishing an "assistance" relationship (in contrast to an "acquisition" relationship) between NHLBI and a recipient, in which substantial NHLBI scientific and/or programmatic involvement with the recipient is anticipated during performance of the activity. The NHLBI purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise facilitating the activity in a "partner" role, but avoiding a dominant role, direction, or prime responsibility. The terms and conditions, 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 anticipated that these terms and conditions will enhance the relationship between the NHLBI staff and the principal investigator(s), and will facilitate the 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 their protocols, including any modification of 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; he/she or another NHLBI scientist may serve on other study committees, when appropriate. The NHLBI Project Scientist (and the other cited NHLBI scientists) may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g., recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment. 3. Awardee(s) agree to the governance of the study through a Steering Committee. Steering Committee voting membership shall consist of the principal investigators (i.e., cooperative agreement awardees) and the NHLBI Project Scientist. Meetings of the Steering Committee will ordinarily be held by telephone conference call or in the Washington DC Metropolitan Area. 4. A Data and Safety Monitoring Board will be appointed by the Director, NHLBI to provide overall monitoring of interim data and safety issues; the Steering Committee will nominate members for this Board. Meetings of the Data and Safety Monitoring Board will ordinarily be held in Bethesda, MD. The NHLBI Project Scientist shall serve as Executive Secretary to the Board.. 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 the continued submission of data centrally to the coordinating center for a collaborative database; the submittal of copies of the collaborative data sets to each principal investigator upon completion of the study; procedures for data analysis, reporting and publication; and procedures to protect and ensure the privacy of medical and genetic data and records of individuals. The NHLBI Project Scientist, on behalf of the NHLBI, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee. 6. Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of project resources or citing the name of the project or the NHLBI support; or special access to project results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI. 7. Awardees are encouraged to publish and to publicly release and 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 the 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. Upon completion of the project, the Data Coordinating Center is expected to put all study intervention materials and procedure manuals into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NHLBI, for the conduct of research at no charge other than the costs of reproduction and distribution. 9. The NHLBI reserves the right to terminate or curtail the study (or an individual award) 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 breach of the protocol, (c) substantive changes in the agreed-upon protocol with which NHLBI cannot concur, (d) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (e) human subject ethical issues that may dictate a premature termination. 10. Any disagreement that may arise in scientific/programmatic matters (within the scope of the award), between award recipients and the NHLBI may be brought to arbitration. An arbitration panel will be composed of three members--one selected by the Steering Committee (with the NHLBI member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by NHLBI, and the third member 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 statutes, regulations and terms of the award. 11. 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 subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided 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 follow the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513), and reprinted in the NIH Guide for Grants and Contracts of March 18, 1994, Volume 23, Number 11 and available on the web at: http://www.nih.gov/grants/guide/1994/94.03.18/notice-nih-guideline008.html. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the 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: http://www.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. LETTER OF INTENT Prospective applicants are asked to submit, by March 1, 1999 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 this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NHLBI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be faxed or sent to Dr. C. James Scheirer at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-710-0267, Email: GrantsInfo@nih.gov. The PHS 398 application kit is also available on the Internet at http://www.nih.gov/grants/forms.htm Additional Material to Include in the Application: It is envisioned that the Principal Investigator (PI) will be an established investigator in biostatistical, epidemiological, cardiovascular, pulmonary, or sleep disorders research with prior experience in complex, large-scale collaborative studies and the delivery of logistical support. It would be desirable for the PI and/or key investigators to have relevant expertise in cardiovascular disease risk factors, epidemiology, and/or sleep disorders medicine. It is not essential that this investigative team be from the same institution. However, if applications involve investigators from different institutions there must be well documented plans for adequate communication, interactions, and facilities to perform analytic and other activities required. The PI must commit a minimum of 20% effort to the DCC. Applicants must demonstrate familiarity with the structure and operations of the SHHS, and be able to interact effectively with Clinical Centers and the reading center using protocols for data exchange and quality control management outlined in the SHHS Manual of Operations. Additional technical information on the operational aspects of the current DCC and specific information for data transfer and documentation can be obtained by contacting the program official listed under INQUIRIES. Applicants should also state their willingness, and that of the institutions involved, to participate in a cooperative and interactive manner with the SHHS Clinical Centers and the NHLBI within the context of this collaborative research program. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. In such a case, a letter of agreement from either the GCRC Program Director or Principal Investigator should be included with the application. Data Coordinating Center applicants should discuss their perception of the DCC role in the SHHS, various aspects of study design, their familiarity with sleep disorders and cardiopulmonary risk factors and diseases, important considerations for making sample size and power calculations, interpretation of baseline and outcome measures, monitoring accuracy of data collection, quality control procedures including training and certification, proposed modifications to processes used by the incumbent DCC; and plans for statistical analysis of results. BUDGET PREPARATION Applications for DCC should present five budget periods of 12 months each using the instructions provided with the research grant application form (PHS 398, rev. 4/98). Applicants are expected to perform all DCC functions with the funding available through this RFA. Future year annual increments in direct costs are not to exceed three percent. Applicants should provide adequate justification for all applicable direct costs. Estimates of staffing needs, including the Principal Investigator, Co- Investigator, other professional and support staff must be included. The suggested level of commitment for the Principal Investigator and Co- Investigator should be 20 percent each. Other personnel such as data center coordinator, data technicians, consultants, and support staff should be carefully outlined and justified in the application. Travel costs should be budgeted for two people to attend 2-3 steering committee meetings in Bethesda each year. Funds should be requested to support up to two meetings of the DSMB each year in Bethesda, MD. Any major equipment items should be well justified. Collaborations or subcontracts that involve the transfer of funds from the grantee to other institutions require formal subcontract agreements with each collaborating institution. Budgets for subcontracts should be prepared using the same guidelines as for the main grant. The costs for the Sleep Reading Center should NOT be included as part of the DCC application. The Reading Center will submit a separate application. The award will be subject to administrative review annually. Applications not conforming to these guidelines will be considered unresponsive to this RFA and will be returned without further review. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. 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, to identify the application as a response to this RFA, check "YES" in item 2 of page 1 of the application and enter the title "Data Coordinating Center for the Sleep Heart Health Study, HL-99-014. Submit a signed, typewritten original of the application 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 must be sent to Dr. C. James Scheirer at the address listed under INQUIRIES. Applications must be received by March 25, 1999. If an application is received after this 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 an application already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and for responsiveness by NHLBI. Incomplete and/or nonresponsive applications will be returned to the applicant without further review. 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 Division of Extramural Affairs, NHLBI, in accordance with the review criteria stated below. The roster of the initial review group will be available via the NHLBI home page. As part of the initial merit review, all applications will receive a written critique and undergo a review 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. Applicants are expected to address issues identified under APPLICATION PROCEDURES. Applications will be judged primarily on the scientific quality and appropriateness of the application, facilities, approach to cost containment, the discussion of considerations relevant to this RFA, expertise of the investigators, their capability to perform the work proposed, and a demonstrated willingness to work as part of the collaborative group and with the NHLBI program official. 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. o 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? o 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? o Innovation: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? o 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 key personnel? o 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 Understanding of the scientific, statistical, logistical, and technical issues underlying multicenter studies, including taking a leadership role in the area of study design, statistics, logistics, data acquisition and management, quality control, data analysis, and overall coordination. o Adequacy of the proposed plans for acquisition, transfer, management, and analysis of data; interactions with the sleep reading center; quality control of data collection and monitoring, and overall coordination of Center activities. o The expertise, training, and experience of the investigators and staff, including the administrative abilities of the Principal Investigator and co-investigators, and the time they plan to devote to the program for effective coordination. o The administrative, supervisory, and collaborative arrangements for achieving the goals of the program, including willingness to cooperate with the participating Clinical Centers and the NHLBI. o Facilities, equipment, subcontracts, and organizational structure to effectively assist Clinical Centers in implementing the protocol and in data collection procedures and in overall coordination of study-wide activities. o Appropriateness of the budget for the work proposed. o The personnel category will be reviewed for appropriate staffing based on the requested percent effort. The direct costs budget request will be reviewed for consistency with the proposed methods and specific aims. Schedule Letter of Intent Receipt Date: March 1, 1999 Application Receipt Date: March 25, 1999 Review by NHLBI Advisory Council: September 16, 1999 Anticipated Award Date: September 30, 1999 AWARD CRITERIA Applications recommended by the National Heart, Lung, and Blood Advisory Council will be considered for award based upon (a) scientific and technical merit, (b) scientific-programmatic requirements, including in this instance, sufficient compatibility of features to make a successful collaborative program a reasonable likelihood, and (c) availability of funds. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: James P. Kiley, Ph.D. National Center on Sleep Disorders Research National Heart, Lung, Blood Institute 6701 Rockledge Drive, Suite 10038, MSC-7920 Bethesda, MD 20892-7920 Telephone: (301) 435-0199 FAX: (301) 480-3451 Email: KileyJ@nih.gov Direct inquiries regarding review matters, address the letter of intent and send two copies of the completed application to: C. James Scheirer, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7220, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3541 Email: jslloj@nih.gov Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Grants Operations Branch National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7154 Bethesda, MD 20892-7926 Telephone: (301) 435-0171 FAX: (301) 480-3310 Email: ZimmermR@gwgate.nhlbi.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.838. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or a Health Systems Agency Review. The PHS strongly encourages all grant and contract 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.
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files. |