Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title

Phase II Clinical Trials of Novel Therapies for Lung Diseases (UM1)

Activity Code

UM1 Multi-Comp Research Project Cooperative Agreements

Announcement Type

Reissue of RFA-HL-10-003

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HL-12-022

Companion FOA

None

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct. Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.838

FOA Purpose

This Funding Opportunity Announcement (FOA) issued by the National Heart, Lung, and Blood Institute, National Institutes of Health, solicits grant applications from institutions/organizations to conduct proof-of- concept Phase II clinical trials that test a novel intervention for a lung disease or a cardiopulmonary disorder from sleep that has the potential to significantly change clinical management.  In addition, each application must include at least one basic research ancillary study tightly related to the clinical question.  

Key Dates
Posted Date
Letter of Intent Due Date

May 16, 2011, January 16, 2012, August 13, 2012

Application Due Date(s)

June 15, 2011, February 15, 2012, September 13, 2012

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

September/October 2011,  June/July 2012, February/March 2012

Advisory Council Review

January 2012, October 2012, May 2013

Earliest Start Date(s)

April 2012, December 2012, July 2013

Expiration Date

September 14, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of 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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this FOA is to solicit research applications to conduct Phase II clinical therapeutic trials that have the potential to advance development of novel therapies for a lung disease or a cardiopulmonary disorder of sleep.  Each application will propose one Phase II interventional trial that will most likely use physiological or biochemical rather than clinical endpoints along with at least one smaller basic ancillary research study that is tightly related to the clinical question.  Although definitive Phase III trials will not be supported, the proposed studies must provide proof of concept for a novel intervention that has high potential for modifying current treatments and could be disease modifying.

Background

Acute and chronic lung diseases are a significant cause of mortality and morbidity in the United States, greatly affecting quality of life, as well as longevity.  Many lung diseases are managed by controlling symptoms, but lack proven pharmacologic or immuno-modulating treatments.  Current treatments are often based on reducing inflammation or preventing cell proliferation with cytotoxic agents that have modest therapeutic efficacy and in most cases have substantial toxicities. Similarly, insufficient sleep and sleep disorders may contribute to cardiopulmonary diseases.

Novel and innovative treatments need testing in lung diseases and sleep disorders.  Basic research studies in cells, tissues, and animal models, investigations of biomarkers and functional genomics have led to a better understanding of the pathogenesis of several of these diseases and suggest new ideas for treatment targets. Mechanistic insights into lung disorders suggest that already approved agents effective in other diseases (e.g., rheumatoid arthritis, diabetes, systemic lupus erythematosus) could be appropriate for treating lung diseases.  Combinations of common drugs with low toxicities could be tested.  Studies supported by this FOA are unlikely to be conducted by industry because of relatively small market shares, or changed or competing company priorities.

Despite the substantial progress made on identifying molecular mechanisms underlying lung diseases, there is little research supported by NHLBI for proof-of-concept, mechanistically-driven small clinical trials.  These are important as they are key to translating basic research advances into clinical research, provide the foundation for larger efficacy trials, and can assist in the understanding of disease processes and perhaps disease sub-groups.

Research objectives

This program enhances opportunities for translational research with the central emphasis on clinical studies.  Research conducted would provide high quality data that could lead to efficacy or Phase III trials in networks or investigator-initiated trials.  Furthermore, this research will provide important pathogenetic understanding of responses to treatments.  Close interaction between clinical and basic researchers required in this program should promote translation of basic science ideas into the clinical setting and expand on ideas from clinical observations that can be pursued in the basic laboratory. 

Each application must propose one Phase II clinical treatment trial.  In this context, Phase II trials are proof of concept studies that will most likely employ (surrogate) physiological (which can include imaging methods) or biochemical endpoints rather than mortality or major clinical endpoints.  The trials should include data collection on well-characterized subjects.  Novel clinical trial designs are encouraged.

Each application must also include at least one but no more than two tightly-related ancillary studies that will provide mechanistic understanding of the clinical question.  The basic ancillary study can be bench-to-bedside or bedside-to-bench and will have budget restrictions (see Section II 2: Funds Available).  The application must be led by the Principal Investigator of the clinical study.    Each ancillary study must be led by a separate individual who may be either a Co-Investigator or a member of a multiple PD/PI team on the the application for the phase II clinical trial network.  This individual should have demonstrated expertise in the proposed field of basic science.   Multiple PD/PIs  are encouraged in order to maximize the interaction and idea exchange.  The ancillary study may be conducted by an investigator at a separate institution through a consortium agreement.

Each project within an application will be scored separately, and separate funding decisions will be made based on the score of the clinical project.  If one or all of the basic ancillary projects do not receive a meritorious score, the clinical trial may still be funded if it is among the most meritorious clinical projects proposed for this FOA.  Consortia with other sites that will assist with patient recruitment are highly recommended. 

Research topics

Clinical studies must include trials of novel drugs, devices, biologics, or management practices for treatment of lung diseases that will provide proof of concept or early testing for efficacy that have the potential to change clinical practice and modify disease.  Where possible, the clinical trial will be a double-blinded placebo-controlled design.

Given the scope of this FOA, it is most likely that appropriate physiological or biochemical endpoints rather than clinical endpoints will be used.  Some examples that may be feasible include but are not limited to those listed below:

Examples of ancillary studies:

Research that would NOT be responsive to this FOA:

This FOA is intended to stimulate novel clinical research that has the potential to significantly change clinical management of lung diseases and sleep disorders.  Applications that propose Phase I (safety) or dose-response studies will be considered not responsive.  Large Scale Phase III efficacy studies will be considered not responsive.   Applications may not propose work that has significant overlap with currently funded programs.  Applications may not compare two agents within a same class of currently used drugs.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New
Resubmission

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The NHLBI intends to commit the following amounts between FY 2012 and FY 2015:

NHLBI, $40,260,000, 8 awards (3 in FY 2012 and 5 in FY 2013)

Award Budget

The total project period for an application submitted in response to this funding opportunity may not exceed 3 years. Direct costs in the first year of funding may be up to $650,000 and up to $1,350,000 per year in years 2 and 3. The amounts will vary depending on the nature of work proposed, but must include at least one basic science ancillary study. 

The clinical study budget is expected to be a majority of the budget. An ancillary study may not exceed $150,000 direct costs/year and the sum of two ancillary studies cannot exceed $250,000 direct costs/year. 

Although the financial plan of NHLBI provides support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.  There will be a rigorous administrative evaluation of recruitment and scientific progress before non-competing renewals are awarded.  The metrics for success and continued funding will be based on achievement of research milestones.  Completion of the proposed clinical trial, new insights into disease mechanism or treatment efficacy, and progression to Phase III efficacy will constitute ultimate success of this program.  

Award Project Period

Scope of the proposed project should determine the project period. The maximum period is 3 years.

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.

Section III. Eligibility Information

1. Eligible Applicants
 
Eligible Organizations

Higher Education Institutions:

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) 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 PHS398 Application Guide.

 The PD/PI of the application must be the leader of the clinical trial.  This individual should have demonstrated experience in design and recruiting into clinical studies or trials.  Each ancillary study must be led by a separate individual who may be either a Co-Investigator or a member of a multiple PD/PI team.  This individual should have demonstrated expertise in the proposed field of basic science. Multiple PD/PIs are encouraged 

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the PHS398 Application Guide.   

Section IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS398 Application Guide, 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.

Letter of Intent

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 research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
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
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express mail zip code: 20817)
Telephone: 301-435-0270
FAX: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the appendix files must be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express mail zip code: 20817)
Telephone: 301-435-0270
FAX: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov 

Page Limitations

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

1.   Description of program and relationship between clinical and ancillary study(ies) - one page.

2.  The research strategy for the clinical trial is limited to a maximum of 12 pages and includes the following subsections:  Background, Preliminary Data, Approach (power, statistics, endpoints).

3.  The research strategy for each ancillary study is limited to a maximum of 6 pages and will include a background indicating relationship to clinical study, specific aims, preliminary studies, research design. 

There will be separate budget pages for the clinical study and the ancillary study(ies).  Budget pages are not included in the page limitation.-

Applications received that exceed these page limitations will not be reviewed.

Research Plan

All instructions in the PHS398 Application Guide must be followed MODFIED ONLY AS DESCRIBED ABOVE IN PAGE LIMITATION SECTION.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the PHS398 Application Guide.

Appendix

Each application should include the complete protocol.

Each Application should include the sample consent form(s).

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

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 only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NHLBI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Additional requirements for submitting an application:

Qualifications and Experience.  The PD/PI must have the necessary experience and expertise to conduct clinical studies in patients.  Previous participation in clinical trials for lung diseases or sleep disorders should be detailed including name of study, role in study and number of patients recruited; participation in studies where recruitment was unsuccessful should also be included. The leader of the ancillary studies should have demonstrated expertise and publications in the field of study. The ancillary study can be conducted through a consortium arrangement with a collaborating institution.

An appropriate time commitment is expected from the principal investigators and co-investigators.  The Principal investigator(s) must commit at least 2.4 person months effort to the clinical project and management of the program; investigators that lead the ancillary studies must devote at least 1.2 person months.  A plan to ensure interaction among all investigators and the communication of ideas and results should be described. Multiple PDs/PIs are strongly encouraged.

Study Population.  Applicants should demonstrate access to a sufficient number of patients to accomplish the protocol by providing specific, objective sources of data on the size of the available population.  This can include documentation of participation in previous clinical trials of similar patients.

Patient access may be accomplished by establishing links with other groups in addition to the applicant’s institution. It is strongly recommended that at least two recruiting centers with a demonstrated record of successful subject recruitment and retention be included in each trial.   If links with other groups are anticipated, the application should include a plan with appropriate letters of support that describes (1) how the applicant will link to and operate with the other groups and (2) how the PD/PI will monitor the quality of the other group’s performance (recruitment and data quality). 

Links with NIH Clinical and Translational Science Award (CTSA) Centers. Applications from institutions that have a CTSA funded by the NIH should identify the resources that would be available to support the proposed research.  Examples of resources include cost sharing, “in-kind” support of personnel or facilities, assay performance, statistical or regulatory support, etc.  A description of the CTSA and how the applicant proposes interacting with it should be included, as well as letter of agreement from either the CTSA Program Director or participating PD/PI.    Applications from institutions without CTSAs will not be disadvantaged.

Research Plan Format. Applicants should submit a research plan with the following subsections: Overview, Clinical Research Protocol Plan and Budget, Basic Science Ancillary study research project(s) and Budget.

Overview (limited to one page): The overview will describe the significance and rationale of the proposed clinical intervention study and describe the relationship of the ancillary study(s) to the clinical project.  The potential for substantially changing clinical management must be addressed.

Clinical Protocol (Specific Aims, 1 page; Research Strategy 12 pages):  The clinical study plan should follow the instructions in the PHS 398 application form and should include research aims, a rationale (i.e., scientific and clinical practice justification for the proposed research), outcome measures (indicating appropriate objective and patient-centered measures for primary and secondary outcomes), study design (including a sound statistical plan, including power analysis, interim reviews, and stopping rules, and timetable). It is expected that all protocols will be performed in a manner consistent with NIH clinical research policies and the United States Food and Drug Administration (FDA) guidelines. Evidence of FDA approval, or a plan for obtaining FDA approval should be provided and will be required at the time of award. 

Basic Science Ancillary Study(ies) (Specific Aims, 1 page; Research Strategy 6 pages each):   At least one but not more than two mechanistic studies that elucidate the biology or mechanism of the intervention must be included in the application.  This proposal should generally follow the instructions in PHS 398 and include research aims, rationale, including relationship to main clinical trial, methods, and expected results.

A budget for each study (clinical and ancillary study(ies) should be presented separately, using the PHS 398 budget page forms; the budget pages are not included in the page limit.  The clinical budget should include a per patient cost (capitation). 

The Protection of Human Subjects Section should include a detailed data and safety monitoring (DSM) plan (as described in the 398 instructions) that will include the roles and responsibilities of a Data and Safety Monitoring Board.  NHBLI will make the final decision whether the DSMB will be institutional or NHLBI operated, depending on the level of risk and other factors.   The DSM should describe the background of potential DSMB members that would be recruited if NHLBI decides that the DSMB should be institutional.  They do not necessarily need to be named in the application.  The budget for the clinical trial should include costs associated with preparation and logistic for DSMB meetings.

This FOA solicits translational research programs that include a clinical trial and at least one but no more than two related ancillary studies.  An ancillary study cannot exceed $150,000 in direct costs; and, if two are proposed, the total requested for the ancillaries cannot exceed $250,000 in direct costs.  Each project will receive a separate merit score.  The clinical trial must be meritorious to receive funding.

Feasibility is an important aspect of these applications. Applicants must demonstrate the ability to enroll the required numbers of patients.  Patient availability and a record of successful subject recruitment and retention at consortia proposed to assist with enrollment must also be documented.  Additional recruiting site(s) are highly recommended.

If an IDE or IND is required, applicants will be required to provide evidence of FDA approval at the time of award.   Evidence of FDA approval or communication will be considered a plus.

A detailed time line for milestones in the study must be provided. This time line must account for IRB and DSMB approval, realistic goals for patient recruitment and follow up, and data analysis and preparation.  Progress will be administratively assessed annually before non-competing awards are made. It is expected that no more than six months from the funding date will be required before patient recruitment begins.

Communication: Communication in this translational program is essential.  Applicants must propose a plan to describe how communication and interactions will be maintained between clinical sites and basic project leaders and study personnel.  If projects or recruitment sites reside at separate institution, any costs for meetings and teleconferences should be included in the budget.

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

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

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.

For this particular announcement, note the following:  The clinical trial and ancillary study(s) will each be evaluated separately and provided separate impact/priority scores.  The scores will not be averaged.  The clinical project impact/priority score will determine the funding priority.  If the ancillary study is not found to be meritorious, it will not be funded.

Overall Impact - Overall

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the trial 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 trial proposed).

Scored Review Criteria - Overall

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 trial that by its nature is not innovative may be essential to advance a field.

Significance

Does the trial/study address an important problem or a critical barrier to progress in the field? If the aims of the trial/study 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 affect clinical practice or progress to a phase III testing?  Does the ancillary study relate closely to the clinical study? Does the clinical project answer an important question that could potentially change clinical practice or lead to testing in larger trials? 

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the trial/study? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, 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?  Does the PDPI of the clinical trial have experience to oversee the study?  Is the PD/PI of the ancillary study a subject expert?  What is the quality of the plan for inclusion of personnel to prepare confidential reports of interim data reports and safety monitoring?  Does the PD/PI of the clinical project identify a Research Coordinator? 

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? 

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the projects? 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? For the clinical study, is the statistical plan sound, including power analysis, interim reviews, and stopping rules?  Is the primary endpoint meaningful?  Is there a realistic plan to recruit the required number of patients?  For the ancillary study: Does the ancillary study complement the clinical study?  

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? 

Additional Review Criteria - Overall

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/priority score, 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. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not applicable

Revisions

Not applicable.

Additional Review Considerations - Overall

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/priority score.

Applications from Foreign Organizations

Not applicable.

Select Agent 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; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHLBI  (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

As part of the scientific peer review, all applications:

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and 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 NHLBI national Advisory Council. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

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.

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

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

 An NHLBI 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 the NIH Project Scientist.

The project scientist (PS) may be a voting member of the Steering Committee and Subcommittees.

Progress will be administratively reviewed prior to issuance of non-competing award.  NHLBI reserves the right to phase out or curtail an individual award in the event of (1) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (3) major breach of a protocol or substantive changes in the agreed-upon protocol with which NHLBI cannot concur; (4) attaining of a major study endpoint before schedule with persuasive statistical significance; or (5) human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility include:

Awardees agree to the governance of the study through a Steering Committee (SC).  All Principal Investigators and a Chairperson, to be appointed by the NHLBI, will comprise the SC.  All major scientific decisions will be determined by majority vote of the SC.  Each Clinical Center, the GIC, and the NHLBI PO will have one vote; the Chair will have one vote in case of a tie.  If a Clinical Center has two principal investigators, each Clinical Center still has one vote.  Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.  

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 regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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.

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. 

Section VII. Agency Contacts

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

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Andrea L Harabin, Ph.D
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10174
Bethesda, MD 20892(Express mail zip code: 20817I)
Telephone: 301-435-0222
Fax: 301-480-3557
Email:harabina@nhlbi.nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892 (Express mail zip code: 20817
Telephone: 301-435-0270
Fax: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Dianna Jessee
Grants Management Specialist
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7170
Bethesda, MD 20892 (Express mail zip code: 20817)
Telephone: 301-435-0166
Fax: 301-451-5462
Email:jesseed@mailnih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.


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