Part I Overview Information


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)

Title: Reducing Cardiovascular Disease Risk Through Treatment of Obstructive Sleep Apnea (U34)

Announcement Type
New

Request for Applications (RFA) Number: RFA-HL-10-023

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 the SF424 (R&R) Application Guide.

Electronic application submission is required for this FoA.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included 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 (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)
93.837, 93.233, 93.838

Key Dates
Release/Posted Date: November 27, 2009
Opening Date: December 21, 2009 (Earliest date an application may be submitted to Grants.gov
Letters of Intent Receipt Date(s): December 21, 2009
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): January 21, 2010
Peer Review Date(s): June-July 2010
Council Review Date(s): August 2010
Earliest Anticipated Start Date(s): September 2010
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: January 22, 2010

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) solicits three-year Clinical Trials Planning Grant Cooperative Agreement (U34) applications from institutions or organizations for pilot studies evaluating the treatment of obstructive sleep apnea (OSA) using positive airway pressure (PAP). The purposes of these studies are twofold. First, the studies should be designed to provide information regarding feasibility of long-term (12 to 18 months) PAP treatment of OSA in patients at risk of CVD. Second, the studies should provide data regarding the effects of PAP on surrogate markers of cardiovascular risk. Outcomes relevant for this FOA are broad and include a range of feasibility metrics (recruitment, retention, randomization, dose of PAP treatment, and design of control groups) and adherence outcomes (measures of patient acceptance of, satisfaction with, and adherence to PAP treatment); sympathetic nervous system hyperactivity; vascular dysfunction; inflammatory markers; platelet aggregation; and neuroendocrine and metabolic function. Populations that are at high risk for cardiovascular disease with established OSA and no prior history of PAP treatment will be the central focus of this initiative. Specific goals are to establish feasibility of long-term PAP treatment in high-risk individuals, to evaluate the potential for such treatment to produce changes in cardiovascular disease risk profiles, and to identify feasibility of study design strategies for future event-driven Phase III clinical trials.

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives
1. Mechanism of Support

2. Funds Available

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contacts
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


1. Research Objectives

Purpose

This FOA solicits three-year Clinical Trials Planning Grant Cooperative Agreement (U34) applications from institutes and organizations for the purpose of conducting preliminary studies to obtain information necessary to guide the design of a Phase III clinical trial to test whether positive airway pressure (PAP) treatment of obstructive sleep apnea (OSA) reduces cardiovascular events. The goals of these studies are twofold. First, the studies should be designed to provide information regarding feasibility of long-term (12 to 18 months) PAP treatment of OSA in patients at risk of CVD. Second, the studies should provide data regarding the effects of PAP on surrogate or intermediate markers of cardiovascular risk and cardiovascular risk factors. Outcomes relevant for this FOA are broad and include a range of feasibility metrics (recruitment, retention, randomization, dose of PAP treatment, and design of control groups) and adherence outcomes (measures of patient acceptance of, satisfaction with, and adherence to PAP treatment); sympathetic nervous system hyperactivity; vascular dysfunction; inflammatory markers; platelet aggregation; and neuroendocrine and metabolic function. Populations that are at high risk for cardiovascular disease with established OSA and no prior history of PAP treatment will be the central focus of this initiative. Specific goals are to establish feasibility of long-term PAP treatment in high risk individuals, to evaluate the potential for such treatment to produce changes in cardiovascular disease risk profiles, and to identify feasibility of study design strategies for future event-driven Phase III clinical trials.

Background

Substantial unexplained variance exists in current models of cardiovascular disease risk after adjusting for known risk factors. Sleep-related breathing disorders are highly prevalent in patients at risk of and with established cardiovascular disease. In particular, obstructive sleep apnea (OSA) is emerging as a significant risk factor for incident myocardial infarction (MI), hypertension, sudden death, and stroke, and for exacerbating the progression of prevalent CVD. However, no population-based studies in the U.S. have assessed the efficacy of treatment of OSA on any CVD outcome or CVD risk factors.

Although figures vary according to the presence or absence of other risk factors, the prevalence of mild to moderate OSA in the general population is reported to be about 15%, with prevalence rates for severe OSA about 5%. Prevalence rates are substantially higher among diabetics (50-95%), obese and overweight adults (25-30%), smokers, men, and elderly men and women (25-30%). These prevalence data may be underestimates because the disorder is significantly under-diagnosed in the general adult population. Data regarding the neurobehavioral consequences of untreated OSA are striking. Debilitating daytime sleepiness, neurocognitive deficits, a 6-12 fold increased risk of motor vehicle accidents, impaired daily activities and function, increased utilization of health-care services, and a diminished quality of life are all associated with under-or untreated OSA. Untreated OSA in the U.S. is estimated to contribute $3 billion in additional medical costs with a total economic burden greater than $100 billion including loss of workplace productivity, occupational injury, and greater health care utilization.

In addition to decreased quality of life, there is increasing evidence that untreated or undertreated OSA significantly impacts cardiovascular health. Retrospective and prospective investigations have established an independent, increased rate of CVD morbidity and mortality in OSA patients, with more significant cardiovascular consequences occurring among patients with existing CVD. OSA patients exhibit an increased prevalence of ischemic heart disease, diabetes, congestive heart failure, acute coronary syndrome, and stroke. There is an increased likelihood of hypertension, and increased likelihood of hypertension-associated target organ damage such as left ventricular hypertrophy.

The pathophysiological pathways most relevant to the study of clinical risk and treatment-related CVD outcomes have not been well delineated. Typically, patients with moderate to severe OSA can experience hundreds of obstructive respiratory events during the night, and each event is associated with oxygen desaturation, hypercapnia, EEG arousal, decreased heart rate variability, and significant and rapid elevations in blood pressure, heart rate, blood pressure variability, vascular resistance. The frequent and acute physiological response to repetitive apneic events during sleep lead to chronic cardiovascular adaptations that persist during the daytime in the absence of hypoxia, including sustained elevation of sympathetic nervous system activity, vasoconstriction, and high blood pressure.

Hypoxia associated with OSA can result in vascular dysfunction, and chronically elevated markers of inflammation including interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and NK cell activity. OSA is also associated with elevated platelet aggregation and may reflect increased circulating catecholamines associated with the disorder. Sleep disturbance associated with untreated OSA is associated with abnormalities in neuroendocrine and metabolic function including cortisol, growth hormone, and decreased insulin sensitivity. The combined effects of OSA on hypoxia, metabolic dysregulation, sympathetic activation, and inflammation indicate a physiological pattern that could significantly contribute to the pathophysiological development of hypertension, stroke, congestive heart failure, and acceleration of the development of atherosclerosis.

Treatment Strategies

Positive airway pressure (PAP) reverses a wide range of airway obstruction conditions and incorporates technology that monitors adherence. PAP is a non-invasive device that supplies a pre-determined and regulated level of room air pressure through a mask or nasal interface. The level of air pressure required to prevent airway collapse is determined during diagnosis (PAP titration study) or can be dynamically adjusted by the device during treatment. Advantages include the availability of internal monitors to record the operating parameters, on/off events, and continually assess if the machine is delivering a therapeutic pressure. Additionally, devices and mask/nasal interfaces are interchangeable, allowing accommodation to meet individual needs based on craniofacial characteristics and comfort. Alternative OSA treatment options, including oral appliances, surgery, weight loss, and airway motor training, produce less complete reversal of airway obstruction and are appropriate for a relatively narrow range of obstruction conditions.

Adherence data regarding short-term treatment with PAP are promising, and individual acceptance of PAP treatment is enhanced with guidance in daily use, motivational interviewing, and follow-up care. However, adherence to long-term (>12 months) PAP use and information regarding optimal dosing of PAP have not been tested in clinical populations. Since PAP is widely recognized as a mainstay treatment approach over the widest range of sleep-related airway obstructions and severities, this initiative will require the use of PAP in studying the potential benefits of OSA treatment on CVD risk factors.

The effects of OSA treatment on cardiovascular events is a clinically important question because a positive finding would result in improved and more rigorous treatment practices for OSA patients at risk of CVD. However, prior to the conduct of a Phase III trial to directly address this question, preliminary information is necessary. This information includes data regarding the feasibility of recruitment, randomization, and retention to long-term PAP treatment among high risk patients with OSA; empirically-derived design decisions regarding selection of sham control groups; and patterns and levels of adherence to long-term OSA treatment, including identification of optimal dosing of PAP in this population.

Information regarding how specific patient characteristics might impact feasibility and adherence will be especially valuable in designing an event-driven trial. Because adherence to PAP can be problematic, the patterns of adherence associated with reductions in CVD risk indicators need to be established. If it can be determined that longer-term treatment studies in cardiac patients are feasible, particularly with regard to adherence to treatment in a high-risk population, and that treatment of OSA improves the pathophysiological markers of disease risk, this would provide compelling evidence to suggest that larger-scale trials examining CV events may be appropriate.

Objectives and Scope

The purpose of this program is to support two transdisciplinary randomized controlled pilot studies to fill critical gaps in our knowledge and provide an enabling foundation for future investigations. These pilot studies will provide scientifically important information even in the absence of a future larger-scale study. Specifically, these studies should be designed to determine:

This program capitalizes on mounting evidence that the pathophysiology associated with OSA increases the risk of CVD risk factors, incident events, and mortality suggesting new opportunities for intervention and the improvement of cardiovascular health. The feasibility and scientific importance of a future Phase III trial testing the impact of PAP treatment on cardiovascular events will be informed by the results of this program. This FOA will require the use of PAP because of its widespread use in OSA. If there is a high rate of adherence for long-term PAP therapy and if the results of this program show that PAP treatment changes biological markers of cardiovascular health, the feasibility and importance of a Phase III trial will be supported. Investigations should be adequately powered to enable an understanding of whether long-term PAP treatment of OSA changes one or more pathophysiological markers of disease risk.

This FOA will not support Phase III trials testing the effects of PAP treatment on cardiac events, but feasibility studies should be designed to incorporate biologic measures of cardiac disease risk. Although comprehensive dose-ranging is not a prime focus of this initiative, adherence data could enable the evaluation of dose in relation to outcomes proposed. This program is not intended to develop or validate new treatments or devices. Animal studies will not be considered responsive to this initiative.

Selected Research Examples

To be responsive, investigative teams must be transdisciplinary and include relevant expertise in cardiovascular disease, sleep medicine, behavioral medicine, clinical trials design, biostatistics, and others as appropriate to the goals of the proposal. Competitive applicants must demonstrate access to high throughput sleep centers that have a demonstrable track record in biomedical research and for achieving high levels of adherence to PAP treatment. Applicants are especially encouraged to work with sleep center resources within new or existing infrastructures such as the NIH Clinical and Translational Science Awards (CTSA) program, Practice-Based Research Networks, Clinical Research Networks, Research Centers in Minority Institutions, Institutional Development Award programs, or other collaborative entities with access to high throughput sleep centers, to leverage existing infrastructure and transdisciplinary expertise.

This initiative will serve as a pilot phase for a future, potential trial testing the effect of successful treatment of OSA on cardiovascular event outcomes. Given the short duration of these studies and the relatively small sample size, it is unlikely that adequate cardiovascular events will be identified. Instead, metrics for success of these pilot studies will be timely recruitment, identification of treatment adherence necessary to show changes in intermediate markers of risk, data regarding feasibility of long-term PAP treatment and design of appropriate control conditions, successful development of a transdisciplinary study team and implementation of the study protocol.

Examples of areas and topics of investigation include, but are not limited to, those described below.

Applicants should provide preliminary evidence of their ability to recruit, randomize, and retain participants, to provide appropriate oversight of participant health and safety, and to maintain high rates of participant follow-up throughout the intervention and follow-up. Studies should incorporate quality control procedures for measurements, data collection, and data management, as well as for assuring fidelity to intervention delivery.

The NHLBI Clinical Research Guide at http://www.nhlbi.nih.gov/crg/index.php, provides helpful information for preparation of clinical study applications.

Program Organization and Coordination

The pilot studies supported by this FOA will not be required to use a common study protocol or central data coordination center. However, after awards are made and whenever possible, research activities will be coordinated through a steering committee process in order to accomplish overall programmatic objectives. Specifically, investigators will be expected to collaborate on developing and reporting standardized measures of key common variables, such as population characteristics and entry criteria, PAP adherence, key protocol characteristics, and key biological outcomes, to facilitate comparison of study outcomes.

Investigators should clearly indicate their willingness and demonstrate their ability to collaborate on the development and use of standardized measurement protocols, identification of eligibility criteria, formative assessment methods, data analysis, and their willingness to collaborate with NHLBI scientists in all aspects of the study. The cooperative agreement mechanism will be used and a Steering Committee formed to facilitate collaboration (see Section VI.2.A, Cooperative Agreement Terms and Condition of Award).

Each awardee is responsible for refining and finalizing their protocols and for conducting the research. Awardees should oversee implementation of their interventions and adherence to their protocols, and assure appropriate quality control procedures are in place. Each awardee will be responsible for training and certification of their personnel.

Applicants should propose budgets which include funds for coordination, planning, attending, and logistics costs associated with DSMB and Steering Committee meetings. Funds to support personnel to prepare the summary reports, including masked analyses and other materials for the DSMB, should be included. Applicants should assume for budgeting purposes that the meetings will be in the Bethesda, MD metro area and will require the attendance of the Principal Investigator and one other person.

Logistics costs associated with meetings will be shared equally by the two awardees and should be included in proposed budgets, including personnel and direct costs associated with the following activities:

Coordination and preparation of scientific publications and dissemination of findings from the studies, as appropriate

The NHLBI - The NHLBI will be substantially involved with the awardees in a partnership. The NHLBI Program Scientist will monitor patient recruitment and study progress, ensure disclosure of conflicts of interest, and assure adherence to NHLBI policies. NHLBI will appoint a Data and Safety Monitoring Board (DSMB) and appoint a chairperson of the Steering Committee among Principal Investigators.

The Steering Committee - The Steering Committee will be an important body for this project. The Steering Committee is composed of the Principal Investigators of the RCTs and the NHLBI Program Scientists, each of whom will have one vote. Each PI will be required to attend Steering Committee meetings in which study plans, findings, and issues of common interests and concerns will be shared and discussed. The Steering Committee will meet in-person two times a year for the first year and once per year thereafter. The Committee will meet by teleconference on at least a monthly basis.

An Independent Data Safety and Monitoring Board (DSMB) - A Data Safety and Monitoring Board will be established by NHLBI to monitor data and oversee participant safety in all of the studies supported by this initiative. The DSMB will report to the Director of the NHLBI. At the first meeting, the DSMB will review the awardees’ protocols. Subsequently, the DSMB will monitor and review recruitment, adverse events, data quality, outcome data, and overall awardee performance. It has the responsibility to review interim data and final data, and recommend whether the protocol should be modified, and whether the study should be continued or should be terminated early. Thus, its ethical responsibilities to the participants, as well as to the integrity of the study, are of paramount importance to the NHLBI. For budgeting purposes, applicants should assume that the DSMB will consist of six individuals and will meet twice each year. One of the meetings each year will be in person.

Applicants should not appoint DSMB members in advance of the peer review, or even inquire about the interest of possible DSMB members, nor should they name potential DSMB members in their applications, because anyone so named or contacted would not be eligible to serve as a member of the peer review committee that will evaluate the applications for scientific merit.

Resources

Applications are sought from transdisciplinary research teams, networks or collaborative groups that have already been formed or will be formed to respond to this FOA. New or existing infrastructures such as the NIH CTSA, Practice-Based Research Networks, Clinical Research Networks, Research Centers in Minority Institutions, Institutional Development Award programs, or other collaborative entities that can form or that have the infrastructure to conduct high-quality, transdisciplinary research on cardiovascular diseases and sleep medicine are strongly encouraged to apply. If such a resource collaboration is proposed, applicants should include a letter of agreement with the application.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This FOA will use the NIH Clinical Trials Planning Grant Cooperative Agreement (U34) award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses “Just-in-Time” information concepts (see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) must use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component.

This funding opportunity will use an NIH cooperative agreement award mechanism. In the cooperative agreement mechanism, the PD(s)/PI(s) retain(s) the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the PD(s)/PI(s), as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

2. Funds Available

NHLBI intends to commit up to $1.5 million in FY10 to fund two applications in response to this FOA with a total of up to $4.5 million available from NHLBI over the three-year period of funding. Each applicant may request a project period of three years and a budget for direct costs of up to $1,500,000 over the three-year period, with a limit of $650,000 in direct costs in any single year. Applicants must adequately budget for personnel, travel and activities associated with coordination of cross-study activities, including identifying common measures, facilitating activities across the sites, coordination and conduct of meetings, and other collaborative activities noted in section 1 above.

Funds for two Steering Committee meetings in year one and one meeting per year thereafter in the Bethesda, MD area must be included in the application. Funds for two DSMB meetings per year, including at least one in-person meeting per year, must also be budgeted and include costs association with the preparation and coordination of meetings. Meeting room and other logistics costs associated with Steering Committee and DSMB meetings will be shared among the two sites.

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.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

NIH grants policies as described in the http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Due to the unique requirements of this FOA, applicants are strongly encouraged to consult with the NHLBI Program Staff as plans for an application are being developed. This early contact will provide an opportunity to clarify the applicant’s understanding of program goals and guidelines, including the scope of projects within the program and program requirements.

Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct and from different principal investigators.

Resubmissions. Resubmission applications are not permitted in response to this FOA.

Renewals. Renewal applications are not permitted in response to this FOA.

Section IV. Application and Submission Information


To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the “Apply for Grant Electronically” button in this FOA or 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:

PDs/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 can submit an electronic application, as follows:

1. Organizational/Institutional Registration in Grants.gov/Get Registered

2. Organizational/Institutional Registration in the eRA Commons

3. Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PDs/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

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 organization/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 the 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. You 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 301-435-0714; Email: GrantsInfo@nih.gov.

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 in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within the SF424 (R&R) application components, 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 “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required 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
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate required budget component.)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” (Section 14 of the Research Plan Component in the SF424 [R&R]), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: December 21, 2009 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): December 21, 2009
Application Due Date(s): January 21, 2010
Peer Review Date(s): June-July, 2010
Council Review Date(s): August 2010
Earliest Anticipated Start Date(s): September 2010

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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 by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: 301-435-0270
FAX: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp and follow Steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

In order to expedite the review, applicants are requested to notify the NHLBI Referral Office by email nhlbichiefreviewbranch@nhlbi.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday – Friday, excluding Federal holidays) to view the application image to determine if any further action is necessary.

Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the IC. Incomplete and non-responsive applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commonshttps://commons.era.nih.gov/commons/. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on the application status in the Commons.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an “Introduction” describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 or renewal award if such costs: (1) are necessary to conduct the project, and (2) 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 approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see the NIH Grants Policy Statement).

6. Other Submission Requirements

Awardees will be expected to coordinate and collaborate with each other on developing, utilizing, and reporting standardized measures of key common variables, criteria, and protocols to facilitate comparison of the study outcomes, and should indicate their willingness to, facilities for, and experience in doing so. The cooperative agreement mechanism will be used and a Steering Committee formed to facilitate collaboration (see Section VI.2.A , Cooperative Agreement Terms and Condition of Award). Applicants should propose budgets which include adequate funds for these purposes, as well as for costs associated with DSMB and Steering Committee meetings.

Additional information or answers to questions on submission requirements are at: http://www.nhlbi.nih.gov/funding/inits/faq-hl-10-023.htm

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information."

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD(s)/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

PHS398 Research Plan Component Sections

Page limitations of the PHS398 Research Plan component must be followed as outlined in the SF424 (R&R) Application Guide. The U34 application Research Plan component of the PHS398 may not exceed 25 pages, including tables, graphs, figures, diagrams, and charts. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not comply with the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Review Process

Applications that are complete and responsive to this FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by National Heart, Lung, and Blood Institute (NHLBI) and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance. Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? What is the potential of the clinical trial to provide meaningful data that would allow progress to Phase III testing? Will the study, as designed, provide important information and scientific knowledge regarding feasibility, adherence (including estimates of dosing), and biomarker information that can be effectively utilized in a subsequence phase III event-driven trial?

Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Is the investigative team transdisciplinary and does it include relevant expertise in cardiovascular disease, sleep disorders medicine, behavioral medicine, clinical trials design, biostatistics, as well as other relevant expertise?

Innovation. Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Will the study provide new scientific knowledge regarding the feasibility of long-term PAP treatment of OSA?

Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for (1) protection of human subjects from research risks, and (2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Is the statistical plan sound, including power analyses, interim reviews, and stopping rules? Are the outcomes meaningful? Is PAP treatment being employed? Is there a realistic recruitment, retention and adherence plan?

Environment. Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Has the applicant demonstrated access to high throughput sleep centers that have a demonstrable track record for treatment adherence to PAP for OSA? Are there collaborations in place that will leverage existing infrastructure and transdisciplinary expertise from CTSAs, Practice-Based Research Networks, Clinical Research Networks, Research Centers in Minority Institutions, Institutional Development Award programs, or other collaborative entities or other existing or newly developed infrastructure? Are there appropriate transdisciplinary skills represented in the research team?

In addition to the above review criteria, the following criteria will be addressed and considered in the determination of scientific merit and the rating.

Collaboration: Have the investigators stated their willingness to collaborate with NHLBI and NIH scientists and staff and with the other awardees supported by this initiative? Is there evidence that the applicant is willing to collaborate on the development and use of key common measures and measurement protocols and share/link data if relevant and applicable? Is there evidence that the applicant is willing to collaborate, where applicable, on identification of eligibility criteria, assessment methods, and to provide information and data for Steering Committee and DSMB reports? Does the applicant address the importance of coordination in order to enhance the value of the research program? Are the proposed approaches appropriate for facilitating coordination? Are appropriate coordinating and resource strategies proposed, and is the budget adequate to support these strategies? Is there evidence of institutional support? Does the applicant have prior experience in collaborative research? Is there availability of adequate data management, programmatic, and statistical support for collaboration?

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects. For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: (1) risk to subjects, (2) adequacy of protection against risks, (3) potential benefits to the subjects and others, (4) importance of the knowledge to be gained, and (5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: (1) the justification for the exemption, (2) human subjects involvement and characteristics, and (3) sources of materials.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: (1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; (2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; (3) adequacy of veterinary care; (4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and (5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Biohazards. Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Additional Review Considerations

As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impac /priority score.

Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agents Research. Reviewers will assess the information provided in this section of the application, including (1) the Select Agent(s) to be used in the proposed research, (2) the registration status of all entities where Select Agent(s) will be used, (3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and (4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Selection Process

Applications submitted in response to this FOA will compete for available funds with all other recommended applications submitted in response to this FOA. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

Not applicable

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., “Funding Restrictions.”

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2. A.1. Principal Investigator Rights and Responsibilities

The PD(s)/PI(s) will have the primary responsibility for all aspects of the study, 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.

Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and governance. Within three years of the end of the period of NHLBI support for the project, data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators, provided such release is consistent with the study protocol and governance and with paragraph 6. In addition, study investigators must establish a plan for making data sets and materials available to the scientific community and to the NHLBI immediately upon completion of the three year period following the end of the period of NHLBI support.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

2. A.2. NIH Responsibilities

An NIH Project Scientist [or “Project Coordinator,” or “Project Collaborator,” or “Intramural Scientist”] will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.
The NHLBI Project Scientist and other NIH scientists will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. The NHLBI scientists may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g., data selection and management, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and possible changes in protocol, observational study monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems.

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 study or data management, follow-up, data reporting, or quality control; (c) major breach of the protocol or substantive changes in the agreed-upon protocol with which NHLBI cannot concur; (d) attainment of a major study endpoint before schedule with persuasive statistical significance; or (e) human subject ethical issues that may dictate a premature termination.

Support or other involvement of industry or any other third party in the study -- 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, 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.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NIH Project Scientist.

2.A.3. Collaborative Responsibilities

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), the NIH Project Scientists, and the Chairperson. Meetings of the Steering Committee will ordinarily be held by telephone conference call or in the metropolitan Washington area.

A Data Safety and Monitoring Board will be appointed by the Director, NIH to provide overall monitoring of interim data and safety issues; the Steering Committee will nominate members for this Board. Meetings of the Data Safety and Monitoring Board will ordinarily be held in the Bethesda, MD, metro area. An NIH scientist other than the NIH Project Scientist shall serve as Executive Secretary to the Board. Because the Board serves as an independent group advisory to the NIH, study investigators will not communicate with Board members regarding study issues, except as authorized by the Board’s Executive Secretary.

The collaborative protocol and governance policies will call for the continued submission of measures or datasets that are common or linked to the coordinating unit for a collaborative database; the submission of copies of the collaborative datasets 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 NIH Project Scientists, on behalf of the NIH, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Catherine M. Stoney, Ph.D.
Division of Prevention and Population Sciences
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10018, MSC 7936
Bethesda, MD 20892
Telephone: (301) 435-6670
FAX: (301) 480-1773
Email: stoneyc@mail.nih.gov

2. Peer Review Contact(s):

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: 301-435-0270
FAX: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

3. Financial/Grants Management Contact(s):

Ms. Charmaine Parsad-RafulowitzStaff Contact Name
Division of Extramural Research ActivitiesDivision
Office of Grants Management Organization
Rockledge II Room 7138Building Number, Room Number
6701 Rockledge DriveStreet Address
Bethesda, MD 20892-NNNN
Telephone: (301) 435-0152-
Fax: 301 451-5462
Email: parsadrc@nhlbi.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, state and federal laws and regulations, including the Privacy Rule.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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 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 http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity 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 think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Inclusion of Women And Minorities in Clinical Research:
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 clinical research projects unless a clear and compelling justification is 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 clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: (a) all applications or proposals and/or protocols must 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) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. 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 (http://grants.nih.gov/grants/funding/children/children.htm).

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 applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information," the "Privacy Rule," on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

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 FOA 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.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the 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.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40-hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


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NIH Funding Opportunities and Notices


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