It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) announces a limited competition opportunity to support the Genomics and Informatics Center (GIC) for the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). The GIC will provide the overall coordination, data management, biorepository management, regulatory, statistical/analytical, and operational support for the program. The GIC also will be responsible for oversight and maintenance of SPIROMICS data and biospecimens, as well as coordination of ongoing and future SPIROMICS-related projects and ancillary studies. The GIC will ensure that SPIROMICS participants are regularly contacted to collect endpoints data and maintain cohort retention.

COPD affects 12-24 million people in the U.S. and is a major cause of disability. Mortality due to COPD has risen sharply over the past several decades despite a major decline in smoking prevalence since the 1960 s. COPD is now the third leading cause of death among adults in the U.S., with an annual mortality of approximately 125,000 persons. There is no cure, and treatments are only moderately effective at relieving symptoms. Novel approaches for prevention and treatment of COPD are urgently needed. While airflow obstruction is the defining characteristic of COPD, there are many other manifestations of COPD, including cough, sputum production, emphysema, exercise impairment, dyspnea, and exacerbations of symptoms. Individual patients often show some characteristics of the disease severely while being relatively normal with respect to others, and within the COPD population there is only poor correlation among the various indicators of disease severity. This heterogeneity suggests that a number of different pathogenetic processes may contribute variably to the development and progression of COPD. From a practical standpoint, heterogeneity imposes a major barrier to progress in clinical research. It requires the study of large numbers of subjects to sample the diverse population, and it weakens the value of any single clinical parameter as a measure of outcome. Despite the fact that recent progress in pathogenetic research has suggested rational pathways and targets for intervention, few clinical trials are being performed. This is mainly due to the large sample sizes and long follow-up times that are required even for seeking proof of concept for a putative therapy. Therapeutic trials in COPD would be greatly accelerated by: 1) a means of selecting pathogenetically homogeneous subpopulations, and 2) the identification of intermediate outcome measures that detect disease progression or treatment response within a time frame of one year or less.

SPIROMICS is an NHLBI-funded program for the collection and analysis of phenotypic, biomarker, genetic, genomic, and clinical data from subjects with COPD for the purpose of identifying subpopulations and intermediate outcome measures. Secondary aims are to clarify the natural history of COPD; to develop bioinformatics resources that will enable the utilization and sharing of data in studies of COPD and related diseases; to create a collection of clinical, biomarker, radiographic, and genetic data that can be used by external investigators for other studies of COPD; and to serve as a platform for ancillary studies. There have been 2,981 participants enrolled in SPIROMICS, and they have been phenotyped and followed at multiple Clinical Sites. Data, including clinical, imaging, and molecular measurements, have been collected longitudinally on these participants, and biospecimens including blood, urine, sputum, and lung samples have been collected from all or a subset.

The SPIROMICS GIC is the organizational center for the SPIROMICS program. The GIC has primary responsibility for developing a plan for achieving study aims; analyzing data; operating a repository of biospecimens; data management; providing overall management and oversight of the study; and disseminating study results. Information about SPIROMICS, including policies and protocols, can be found at http://www2.cscc.unc.edu/spiromics/.

The original SPIROMICS program was funded through contracts between NHLBI and six Clinical Centers, a Radiology Center, and a GIC. Each of these components has representation on the SPIROMICS Steering Committee (SC), which acts as the governing body for the study. The work supported through the SPIROMICS contracts has been completed, but NHLBI continues to support the maintenance of biospecimens collected under these contracts through a contract supporting the GIC. Future research using the SPIROMICS cohort may involve continued longitudinal follow-up of these study participants, possibly including the collection of additional biospecimens, as well as ancillary studies using SPIROMICS biospecimens and/or participant involvement.

This FOA seeks to support, under the direction of NHLBI, a continuation for certain activities of the SPIROMICS GIC such that the study data and biospecimens are maintained and distributed as appropriate, study participants continue to be contacted for endpoints assessment and retention purposes, ancillary and associated studies are managed and coordinated, and SPIROMICS and NHLBI policies, including regulatory policies, continue to be enforced. Apart from roles of the GIC that would depend upon other future funding for research involving the SPIROMICS cohort, activities supported by this FOA will include obligations to:

• Obtain and maintain necessary IRB approval(s).
• Assist the Clinical Sites and ancillary study PD/PIs with electronic submission of SPIROMICS data and the correction of entry errors.
• Manage the study Clinical Sites.
• Provide data quality control and assurance and error correction.
• Monitor study progress. Prepare interim summaries of study activities and outcomes for review by the Observational Study Monitoring Board (OSMB).
• Manage continued longitudinal follow-up of SPIROMICS participants. Ensure that participants are contacted on a quarterly basis.
• Report adverse events and unanticipated problems in accordance with NHLBI/NIH policies.
• Participate with SPIROMICS investigators in the preparation of presentations and manuscripts.
• Participate in discussions of scientific goals of the study.
• Maintain a repository of study biospecimens collected under the SPIROMICS contracts and assist the Clinical Sites with shipments of new biological specimens obtained during future clinical visits as they become available. Oversee shipment of biospecimens for approved analyses. Manage the transfer of data to the GIC, including the results from biospecimen analyses.
• Oversee SPIROMICS policies and procedures, including the SPIROMICS Publications and Ancillary Studies Policies. Ensure that use of SPIROMICS data and biospecimens is consistent with consent restrictions and has obtained appropriate approval from the SC and NIH, as needed.
• Ensure that new data is incorporated into the limited access dataset.

This Cooperative Agreement will support the storage of the SPIROMICS biorepository. Biospecimens collected with funding from the SPIROMICS contracts are and will remain property of NHLBI and the US Government. Possession of these SPIROMICS biospecimens during the period of the award through bailment will not give the GIC any claim of ownership over them. Any use or transfer of these SPIROMICS biospecimens to a third party for analysis will require prior approval by NHLBI. NHLBI may take exclusive custody and control of these SPIROMICS biospecimens at its reasonable discretion upon termination or expiration of this cooperative agreement.

SPIROMICS data and biospecimens will continue to be shared with the scientific community, including investigators not associated with SPIROMICS, according to NHLBI and SPIROMICS policies. New data collected with the SPIROMICS cohort under funding from other grants and/or additional funding sources will be included in the SPIROMICS dataset according to the NHLBI Data Sharing Policy (https://www.nhlbi.nih.gov/research/funding/human-subjects/data-sharing). The GIC will update the limited access SPIROMICS dataset on a semi-annual basis. SPIROMICS biospecimens will continue to be made available to the scientific community according to the SPIROMICS Ancillary Studies Policy (http://www2.cscc.unc.edu/spiromics/as_home). Award is dependent upon a signed Materials Transfer Agreement with NHLBI.

NHLBI Program staff and Office of Grants Management staff are responsible for the overall management of the Cooperative Agreement. In addition to regular grant stewardship, the NHLBI Project Scientist will be involved substantially with the awardee as a partner, consistent with the Cooperative Agreement mechanism.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Eligibility is limited to the current Genomics and Informatics Center (GIC) of the SPIROMICS program.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
National Institutes of Health
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: 301-435-0270
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy:

The Research Strategy must discuss the overall approach to coordinate and administer the SPIROMICS program. Plans for study management, dissemination of results, administration, oversight of regulatory responsibilities, and maintenance of SPIROMICS data and biospecimen repositories should be described. Applicants must specifically address:

• Regulatory oversight: Describe how human subjects oversight will be implemented, including IRB approvals and OSMB management and reporting of adverse events and unanticipated problems in accordance with NHLBI/NIH policies.
• Data management: Describe how data from SPIROMICS-related activities will be managed, including quality control measures. Describe how data management and quality control procedures will ensure the safety of participants. Applicants should explain how data management systems will be flexible enough to accommodate the changing needs of the program over time. Description should include a plan for the transfer of study data collected using biospecimens, from ancillary studies or other activities, to the SPIROMICS dataset.
• Study management: Describe how management will be conducted, including organizing and conducting telephone conference calls, management of Working Groups and Sub-Committees, recording of study progress, and enforcement of study policies. Applications should address how the proposed GIC will address the needs of SPIROMICS, and how the scope of activities proposed will meet those needs.
• Continued contact with participants: Describe how continued longitudinal follow-up of SPIROMICS participants will be managed, in particular ensuring that participants are contacted on a quarterly basis.
• Biorepository maintenance: Describe how a biorepository of study biospecimens collected under the SPIROMICS contracts will be maintained. Applicants should describe biorepository facilities, and plans for maintenance and organization of existing and future SPIROMICS biospecimens. Opportunities to leverage institutional resources should be detailed.
• Previous experience of proposed team: Applications should demonstrate the experience the proposed team has coordinating collaborative clinical research, and in particular with project coordination, administration, data management and quality control, acquisition and storage of biospecimens, statistical/analytical support, monitoring safety, regulatory support, and fiscal management. Applications should also address team experience with COPD pathobiology. Applicants should demonstrate synergistic knowledge of current best practices related to the SPIROMICS study, in particular in the areas of biorepository and database maintenance and study management. Past experience of the proposed team with the coordination of the collection, tracking, storage, and retrieval of high quality biospecimens should be described.

Letters of Support:

Letters of institutional and departmental support for participation in SPIROMICS are required. In addition, a letter of support from the SPIROMICS Steering Committee is required.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Applicants are expected to describe procedures for sharing SPIROMICS biospecimens and data with scientific investigators, and plans for adding new data to the limited access SPIROMICS dataset on a semi-annual basis, as appropriate and consistent with achieving the goals of the program. Descriptions should include plans for advertising these resources to the wider scientific community.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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 only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact 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 review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific 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.

Does the proposed Center address the needs of the research program that it will coordinate? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research project?

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing COPD research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this FOA:

How strong is the application in demonstrating that the PDs/PIs and Key Personnel have the experience and capabilities in multidisciplinary GIC functions, including project coordination, administration, data management and quality control, acquisition and storage of biospecimens, statistical/analytic support, monitoring safety, regulatory support, and fiscal management? What experience does the GIC possess in COPD pathobiology to facilitate study goals?

Does the application propose novel management strategies in coordinating the research program the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of management strategies proposed?

Specific to this FOA:

Where appropriate, does the proposed GIC utilize current best practices to improve the knowledge and/or skills of the study, in particular in the areas of biorepository and database maintenance and study management? Does the applicant propose innovative approaches to leverage institutional resources to augment the capabilities and mission of the SPIROMICS study, particularly in terms of biospecimen storage?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research program the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the program is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the program? Is an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Specific to this FOA:

What are the strengths and weakness of the GIC s approaches to study management, dissemination of results, administration, oversight of regulatory responsibilities, and maintenance of data and biospecimen repositories as described in this FOA?

Are the data management and quality control procedures adequate to ensure the safety of participants in multi-institutional clinical studies? How strong is the evidence for the ability of the GIC to coordinate the collection, tracking, storage, and retrieval of high quality biospecimens for use by SPIROMICS and non-SPIROMICS investigators? How effective will plans be for continued longitudinal follow-up of SPIROMICS participants, in particular for ensuring that participants are contacted on a quarterly basis?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Has the applicant proposed adequate plans to support the NHLBI-appointed OSMB?

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research program it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Specific to this FOA:

Are data management systems flexible enough to accommodate the changing needs of the program over time? What facilities does the applicant have for biorepository maintenance, and how will they enable stable storage and organization of existing and future SPIROMICS biospecimens?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

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. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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).

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; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Heart, Lung, and Blood Institute in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Heart, Lung, and Blood Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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 eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following 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 75 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.

The PD(s)/PI(s) will have the primary responsibility for:

The GIC PDs/PIs play an important role in all aspects of SPIROMICS, including monitoring retention of study participants, assuring the quality of study participant protocol adherence, assuring the accurate and timely transmission of data, analyzing and interpreting data, preparing publications, maintaining a biorepository, implementing SPIROMICS policies, and working with the Clinical Sites and the NHLBI to disseminate research findings in a timely manner. Awardees must agree to the governance of the study through a Steering Committee.

Awardee responsibilities will include maintaining a repository of study biospecimens collected under SPIROMICS contracts and assisting the Clinical Sites with shipments of new biological specimens obtained during future clinical visits as they become available. The repository must have adequate safeguards to ensure the maintenance of biospecimens without degradation, even in events such as power outage. Biospecimens collected with funding from the SPIROMICS contracts will remain property of NHLBI. Possession of these SPIROMICS biospecimens during the period of the award through bailment does not give the awardee any claim of ownership over them. Any use or transfer of these biospecimens to a third party for analysis will require compliance with SPIROMICS and NHLBI policies, and prior approval by NHLBI staff. Awardees will be responsible for ensuring that the use of biospecimens is consistent with participant consent as well as IRB and OSMB approvals. NHLBI may take exclusive custody and control of SPIROMICS biospecimens collected under the original contracts at its reasonable discretion upon phase-out or expiration of this Cooperative Agreement.

Study PDs/PIs are encouraged to publish and disseminate results and other products of the study in accordance with study protocols and governance. Awardees will retain custody of and have primary rights to the data and software developed under this award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. All collected study data are expected to be made publicly available consistent with the study protocol and according to NHLBI Policy (http://www.nhlbi.nih.gov/research/funding/human-subjects/data-sharing). Data available to individuals who are not study investigators must be updated on an ongoing semi-annual basis.

Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. Participation by the third party; involvement of study resources, citing the name of the study or NHLBI support, or special access to study results, data, findings or resources requires notification and concurrence by NHLBI. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

NHLBI staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NHLBI will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, and will monitor participant retention and study progress, ensure disclosure of conflicts of interest, and ensure adherence to NHLBI policies. In addition to the NHLBI Project Scientist, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement, and will be identified in the Notice of Award. However, NHLBI may elect to have a dual-role approach where a single individual may act as the NHLBI Project Scientist and Project Officer. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. Because it is anticipated that the Project Scientist/Program Official will participate in activities that rise to a level of involvement that results in conflicts of interest, for example, co-publication, other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award.

The NHLBI reserves the right to phase-out or curtail the award in the event of: (a) failure to develop or implement mutually agreeable collaborative protocols; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c) major breach of the protocols or substantive changes in the agreed-upon protocols with which NHLBI cannot concur; (d) attaining of a major study endpoint before schedule with persuasive statistical significance; or (e) human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility Include:

Awardee(s) agree to the governance of the study through a Steering Committee. The Steering Committee will have primary responsibility for identification of priority areas for research, the conduct of protocols, data analysis, and the preparation of publications and dissemination products. The Steering Committee will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of SPIROMICS activities and operations.

The Genomics and Informatics Center (GIC) will have representation on the SPIROMICS Steering Committee. All major scientific decisions will be determined by majority vote of the Steering Committee.

In-person meetings of the Steering Committee will ordinarily be held in Bethesda, MD, up to two times a year, and by telephone conference call monthly. Steering Committee members must make every effort to attend Steering Committee meetings and participate in conference calls. Should the PD/PI find it impossible to attend a Steering Committee meeting or conference call, he/she is required to notify the NHLBI Program Officer and/or Steering Committee Chair of the expected absence and ensure attendance by their designated alternate.

The Steering Committee and the GIC will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of Network activities and operations.

An independent Observational and Safety Monitoring Board (OSMB) will be appointed by the Director, NHLBI to provide overall monitoring of interim data and safety issues. Meetings of the OSMB will ordinarily be held in Bethesda, MD. An NHLBI scientist other than the NHLBI Program Official or Project Scientist will serve as Executive Secretary to the Board. Because the OSMB serves as an independent group advisory to the NHLBI, study investigators shall not communicate with OSMB members regarding study issues, except as authorized by the Board's Executive Secretary.

Dispute Resolution:

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 Dispute Resolution. A Dispute Resolution 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 dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Lisa Postow, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0202
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]

Anthony Agresti
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0166
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 Part 75.