rfa-eh15-002 amend 1.pdf

Centers for Disease Control and Prevention

National Center for Environmental Health Extramural Research Program Office

Development and validation of laboratory procedures using next generation sequencing technologies to assess genes causing severe combined immune deficiency (SCID) in state newborn screening laboratories.

RFA-EH-15-002

Application Due Date: 04/06/2015

Development and validation of laboratory procedures using next generation sequencing technologies to assess genes causing severe combined immune deficiency (SCID) in state newborn screening laboratories.

RFA-EH-15-002

TABLE OF CONTENTS

Part 1. Overview Information

Key Dates Required Application Instructions Executive Summary

Part 2. Full Text

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 1. Overview Information Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations National Center for Environmental Health Extramural Research Program Office (NCEH ERPO) National Center for Environmental Health (NCEH) Funding Opportunity Announcement (FOA) Title Development and validation of laboratory procedures using next generation sequencing technologies to assess genes causing severe combined immune deficiency (SCID) in state newborn screening laboratories.

Activity Code

Funding Opportunity Announcement Type New Funding Opportunity Announcement Number

RFA-EH-15-002

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.070 Category of Funding Activity:

Health FOA Purpose This FOA is to develop, improve, and implement laboratory techniques to assess babies born with severe combined immunodeficiency (SCID) and other primary immunodeficiencies using next generation sequencing technologies as a second tier test in state newborn screening laboratories. CDC seeks to evaluate the potential of using next generation sequencing technologies in the state newborn screening laboratory setting. Results of this activity will be used to inform other state newborn screening laboratories about the feasibility of using next generation sequencing technologies in the state newborn screening laboratory setting to evaluate babies that screen positive for SCID and other primary immunodeficiencies. The ultimate goal is to improve treatment outcomes for babies with SCID or other primary immunodeficiencies.

The purpose of this FOA is to provide additional clarifying information based on questions received from potential applicants during the Pre-Application Conference Call or as a result of direct communication with the Scientific Program Official. A summary of the "questions and answers" begins on page 29.

Key Dates Publication Date: To receive notification of any changes to RFA-EH-15-002, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link. An email address is needed for this service.

Letter of Intent Due Date: 03/11/2015

Application Due Date: 04/06/2015

On-time submission requires that electronic applications be error-free and made available to CDC for http://www.grants.gov

On-time submission requires that electronic applications be error-free and made available to CDC for processing from eRA Commons on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov/eRA Commons no later than 5:00 PM U.S. Eastern Time. Note:

HHS/CDC grant submission procedures do not provide a period of time beyond the application due date to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review: 07/07/2015 This is an approximate date; actual date will be in July 2015.

Secondary Review: 07/22/2015 This is an approximate date; actual date will be in July 2015.

Estimated Start Date: 09/30/2015 This is an approximate date; actual date will be in September 2015.

Expiration Date: 04/07/2015 Due Dates for E.O. 12372: Due no later than 60 days after the application receipt date.

Required Application Instructions It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise in this FOA. 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.

Note: The Research Strategy component of the Research Plan is limited to 25 pages.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary Purpose. This FOA seeks research to develop, improve, and implement laboratory techniques to assess babies born with severe combined immunodeficiency (SCID) and other primary immunodeficiencies using next generation sequencing technologies as a second tier test in state newborn screening laboratories.

Mechanism of Support. Cooperative Agreement.

Funds Available and Anticipated Number of Awards. NCEH intends to commit approximately $350,000 in FY 2015 to fund one application. The maximum amount of the award for the first 12-month budget period is $350,000 (direct and indirect costs). The actual amount awarded will depend upon the availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed research will vary from application to application, it is also anticipated that the size and duration of the award may also vary.

Budget and Project Period. The estimated total funding (direct and indirect costs) for the first 12-month budget period is expected to be $350,000 (direct and indirect costs) and the estimated total funding for the entire 3-year project period is expected to be $1,050,000 (direct and indirect costs). The project period will run from 09/30/2015 to 09/29/2018.

Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. Application and Submission Information of this announcement.

Eligible Institutions/Organizations. Institutions/organizations listed in Section III.1 are eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. NOTE: CDC does not make awards to individuals directly. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply.

Number of PDs/PIs. Co-principal investigators from different state newborn screening programs are encouraged for this FOA; their names must appear on the face page of the application. However, one principal investigator must be designated as the contact PI. For institutions/organizations/state programs 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 SF 424 (R&R) Application Guide.

Number of Applications. Eligible applicant institutions may submit more than one application, provided that each application is scientifically distinct. However, applicant institutions can submit only one grant application with the same principal investigator.

Application Type. New.

Special Date(s).

Letter of intent, if it is submitted, is due 30 days after publication.

A pre-application teleconference call will conducted on February 25, 2015, from 2:00 – 3:30 pm Eastern Time to address prospective applicants’ questions regarding FOA EH15-002, Development and validation of laboratory procedures using next generation sequencing technologies to assess genes causing severe combined immune deficiency (SCID) in state newborn screening laboratories.

PARTICIPANT ACCESS INFORMATION

CALL DATE: February 25, 2015 CALL TIME: 2:00 Eastern Time CALL DURATION: 1 hour 30 minutes CALL LEADER: Susan Neurath Toll-Free Number: (855)-644-0229 Passcode: 8636049 #

Application Materials. See Section IV.1 for application materials.

Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (770) 488-2783.

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority

Awards are made under the authorization of Sections of the Public Health Service Act as amended and under the Code Federal Regulations. Awards are made under the authorization of Section 301 of the Public Health Service Act [42 U.S.C. Section 241], as amended.

1. Background and Purpose

Background

Newborn screening programs help promote health and prevent death by testing newborns for diseases that require immediate medical treatment but are not apparent at birth. Within days of birth, more than 98% of the 4 million babies born in the United States each year have blood drawn and collected on specific filter paper cards. These dried blood spots are immediately transported to state public health newborn screening laboratories for analysis of specific biomarkers that help identify life-threatening diseases requiring early intervention.

Routine primary newborn screening tests favor the identification of as many affected newborns as possible while trying to limit the number of false positive tests. False positive test results add to newborn screening program costs and cause unnecessary stress and anxiety to families. One approach to achieve the best algorithm for screening involves combining primary, or first-tier, screening tests with second-tier tests to improve screening performance and provide additional information that would be helpful to health care professionals.

Since 1978, CDC has supported the state newborn screening laboratories through the Newborn Screening Quality Assurance Program. The Newborn Screening Quality Assurance Program helps state newborn screening laboratories ensure that both first-tier and second-tier testing accurately detects the biomarkers associated with newborn screening disorders. For over 30 years, the CDC’s Newborn Screening Quality Assurance Program has performed this essential public health service, supporting the quality and accuracy of screening tests for millions of babies worldwide. The Program has grown from supporting 1 disorder in 1978 for 31 laboratory participants to more than 50 disorders for more than 600 laboratory participants in 2014.

Babies born with severe combined immunodeficiency (SCID) and other primary immunodeficiencies typically appear normal at birth and often have no family history of immunodeficiency. SCID and other primary immunodeficiencies alter the ability of the immune system to function properly, which makes babies susceptible to repeated infections and other health problems. Prior to the availability of newborn screening, most babies born with SCID and other primary immunodeficiencies were not identified until development of life-threatening infections that caused death before one year of age. In addition, babies with SCID are vulnerable to complications from the recommended course of pediatric vaccinations, especially the live rotavirus vaccine [1]. A 2002 study showed that babies with SCID who received a bone marrow transplant prior to three months of age had a greater than 95% chance of being cured of SCID [2]. A 2014 study showed survival for children with SCID receiving transplants before 3.5 months of age was significantly better than that for children with SCID receiving transplants after 3.5 months of age [3]. Evidence from this and other studies indicate that early detection via newborn screening is an essential factor in decreasing infant mortality from this disorder. Based on newborn screening data from 11 state newborn screening programs over the past six years, SCID affects 1 in 58,000 births (95% CI, 1/46,000-1/80,000) [4]. The early detection of these babies via newborn screening can prevent unnecessary morbidity and mortality.

In 2010 the Secretary’s Advisory Committee on Heritable Disorders in Newborn Screening and Children, recommended the addition of SCID as the 30th core condition to the recommended uniform screening panel (RUSP). Later that same year, the United States Secretary of Health and Human Services approved the addition of SCID to the RUSP. As of January 2015, 27 states and the District of Columbia include SCID as part of their statewide newborn screening panel. In 2015, CDC will initiate a new funding opportunity announcement to award up to $600,000 through cooperative agreements to state or territorial public health newborn screening programs that do not currently conduct statewide SCID newborn screening.

Current newborn screening for SCID involves the detection of the presence or absence of a biomarker called T-cell receptor excision circles (TRECs). TRECs are composed of a fragment of DNA excised from T-cell receptor genes in the human genome during the differentiation of T-cells in the thymus. This extra-chromosomal non-replicating DNA fragment circularizes and the newly formed junction of these two ends is a unique sequence providing a surrogate marker for T-cell maturation. TRECs can be amplified and quantitated using quantitative polymerase chain reaction (PCR). Babies with SCID have low or no TRECs.

There are many genes associated with T-cell maturation, and mutations in these genes can result in SCID.

Once a baby has screened positive for SCID using the first tier assay to detect TRECs, knowledge of the mutation or mutations in genes that cause SCID can be assessed by second-tier genetic testing. This genetic testing is conducted on the original blood spot and may provide additional information about the baby to inform treatment options. Many different genetic mutations—both known and unknown—can cause SCID.

To efficiently analyze the many genes that can be causative of SCID, high-throughput, or next generation, To efficiently analyze the many genes that can be causative of SCID, high-throughput, or next generation, sequencing methods are required. These methods are capable of evaluating the sequence for multiple mutations on multiple genes at the same time, as would be required for an appropriate second-tier test. To be effective for state newborn screening programs, this test would need to be able to provide robust information from a small amount of DNA extracted from the dried blood spot and be flexible enough to add new target genes as they are identified. Second-tier genetic screening for SCID performed in the public health laboratory would ensure equitable access to this knowledge.

Purpose

This FOA is to develop, improve, and implement laboratory techniques to assess babies born with severe combined immune deficiency (SCID) and other primary immunodeficiencies using next generation sequencing technologies as a second tier test in state newborn screening laboratories. CDC seeks to evaluate the potential of using next generation sequencing technologies in the state newborn screening laboratory setting. Results of this activity will be used to inform other state newborn screening laboratories about the feasibility of using next generation sequencing technologies in the state newborn screening laboratory setting to evaluate babies that screen positive for SCID and other primary immunodeficiencies. The ultimate goal is to improve treatment outcomes for babies with SCID or other primary immunodeficiencies.

The purpose of this FOA is to provide additional clarifying information based on questions received from potential applicants during the Pre-Application Conference Call or as a result of direct communication with the Scientific Program Official. A summary of the "questions and answers" begins on page 29.

References

1.Centers for Disease Control and Prevention (CDC). Addition of severe combined immunodeficiency as a contraindication for administration of rotavirus vaccine. MMWR Morb Mortal Wkly Rep. 2010 Jun 11;59(22):687-8. PubMed PMID: 20535093.

2.Myers LA, Patel DD, Puck JM, Buckley RH. Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood.

2002 Feb 1;99(3):872-8. PubMed PMID: 11806989.

3. Pai SY, Logan BR, Griffith LM, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014 Jul 31;371(5):434-46. doi: 10.1056/NEJMoa1401177. PubMed PMID:

25075835; PubMed Central PMCID: PMC4183064.

4.Kwan A, Abraham RS, Currier R, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014 Aug 20;312(7):729-38. doi: 10.1001/jama.2014.9132.

PubMed PMID: 25138334.

Healthy People 2020 and other National Strategic Priorities

This FOA directly addresses Healthy People 2020 priority area Maternal, Infant, and Child Health (MICH)-32: Increase appropriate newborn blood-spot screening and follow-up testing. Funding for states or territories to implement newborn screening for SCID will result in more newborns screened, identified, and referred for treatment. For more information, see www.healthypeople.gov.

Additionally, this research is consistent with the Secretary of Health and Human Services’ adoption of SCID as a core condition on the Recommended Uniform Screening Panel (http://www.hrsa.gov/advisorycommitt ees/mchbadvisory/heritabledisorders/recommendedpanel/index.html).

http://www.healthypeople.gov/ http://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/recommendedpanel/index.html

Public Health Impact

SCID is a deadly disease that affects one in 40,000-100,000 live births. However, SCID is treatable if detected early in life. This activity seeks to improve newborn screening techniques for SCID and primary immunodeficiencies in state newborn screening laboratories which may improve treatment outcomes. Lessons learned will be shared with other state newborn screening laboratories.

Relevant Work

CDC’s research and programs work to improve the effectiveness and availability of infant blood tests included in the state newborn screening systems.

In 2008, CDC awarded research funding via RFA-EH-08-002 to Wisconsin and Massachusetts to demonstrate the feasibility of statewide newborn screening for SCID. In 2011, CDC supported research in Michigan and Minnesota through RFA-EH-11-001 to implement SCID newborn screening programs in their states. In 2013, CDC provided non-research funds via RFA-EH-13-1303 to Georgia, Oklahoma, and Virginia to build capacity and implement SCID programs.

This FOA seeks research that builds on the previous successful research and non-research CDC-funded projects to implement newborn screening for SCID in state or territorial newborn screening laboratories.

2. Approach

Objectives/Outcomes

This research project seeks to utilize current next generation sequencing technologies to develop second-tier methods to identify mutations in genes that cause SCID and other primary immunodeficiencies in the high-throughput newborn screening laboratory setting. The immediate goal is to expand state newborn screening laboratory capacity to develop and implement targeted next generation sequencing approaches for genes associated with SCID and other primary immunodeficiencies. The ultimate goal is to improve treatment outcomes for babies born with SCID and other primary immunodeficiencies.

Research activities will address all of the following:

1. Develop and validate robust next generation sequencing methods for accurate and timely delivery of results consistent with the high throughput needs of state newborn screening programs. The proposed method should be inclusive of genes known to cause SCID and other primary immunodeficiencies, with appropriate coverage, and be scalable for the addition of new genes, as appropriate.

2. Ensure consistent high quality performance characteristics of the new method.

3. Partner with the CDC newborn screening laboratories to create and evaluate suitable quality assurance materials.

4. Partner with medical specialists to assure appropriate correlation for diagnosis and treatment.

5. Provide education and training for laboratory scientists, healthcare providers, state newborn screening program officials, and primary care physicians about state newborn screen tests for mutations in SCID genes.

6. Conduct a retrospective evaluation of screened positive SCID samples either within-state or in collaboration with partner state programs to validate the method and evaluate mutations in genes that may cause SCID and other primary immunodeficiencies.

Target Population

The target population of this research focuses on infants born in any type of US hospital, but will also be relevant to the infants’ parents and health care providers.

Collaboration/Partnerships

In order to conduct this critical research, applicants are expected to represent or have a well-developed, established collaboration with an active state newborn screening program capable of testing for SCID and other primary immunodeficiencies. The primary research team should include investigators experienced with medical care for newborns with SCID and other primary immunodeficiencies and investigators experienced with next generation sequencing technologies. Documentation of the collaboration is illustrated by letters of support, memorandum of understanding or agreement, or an interagency plan that details the nature and extent of the involvement from the performing organization and outside entities. Documentation of the collaboration must be included in the appendix of the application. Applications without documentation of collaboration with an active state newborn screening program capable of testing for SCID and other primary immunodeficiencies will be considered nonresponsive and will not be submitted for review.

Evaluation/Performance Measurement

Applicants are expected to provide measures of effectiveness that will demonstrate the accomplishment of the proposed project objectives. Applicants are expected to develop and conduct a retrospective evaluation of screened positive SCID samples to validate the sequencing method and evaluate mutations in genes that may cause SCID and other primary immunodeficiencies.

Translation Plan

Research findings should be disseminated through publications, including articles in peer reviewed journals and “Research Briefs” for diverse audiences, as well as presentations at professional conferences and other venues. Relevant research findings should be disseminated through education and training for laboratory scientists, healthcare providers, newborn screening program officials, and primary care physicians. An explanation for how the scientific findings will be translated into public health programs, policies or practice should be included.

Section II. Award Information

Funding Instrument Type: 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 - An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round.

Estimated Total Funding: $350,000

NCEH intends to commit approximately $350,000 in FY 2015 to fund one application. The estimated total funding for the first 12-month budget period is expected to be $350,000 (direct and indirect costs) and the estimated total funding for the entire 3-year project period is expected to be $1,050,000 (direct and indirect costs). The project period will run from 09/30/2015 to 09/29/2018.

Anticipated Number of Awards: 1

Awards issued under this FOA are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Award Ceiling: $350,000 Per Budget Period Award Floor: $350,000 Per Budget Period Total Project Period Length: 3 year(s) Throughout the project period, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (http://www.hhs.gov/ asfr/ogapa/aboutog/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category: State governments

County governments City or township governments Special district governments Independent school districts Public and State controlled institutions of higher education Native American tribal governments (Federally recognized) Public housing authorities/Indian housing authorities Native American tribal organizations (other than Federally recognized tribal governments) Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Nonprofits without 501(c)(3) status with the IRS, other than institutions of higher education Private institutions of higher education For profit organizations other than small businesses Small businesses Others (see text field entitled "Additional Information on Eligibility" for clarification) Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility"

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

Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education:

Nonprofits (Other than Institutions of Higher Education) http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf

Governments:

Eligible Agencies of the Federal Government U.S. Territory or Possession

Other:

Native American tribal organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Regional Organizations Bona Fide Agents: a Bona Fide Agent is an agency/organization identified by the state as eligible to submit an application under the state eligibility in lieu of a state application. If applying as a bona fide agent of a state or local government, a legal, binding agreement from the state or local government as documentation of the status is required. Attach with "Other Attachment Forms" when submitting via www.grants.gov.

2. Foreign Organizations Foreign Organizations are not eligible to apply.

Foreign components of U.S. Organizations are not eligible to apply.

For this announcement, applicants may include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Special Eligibility Requirements

This FOA seeks research to develop, improve, and implement laboratory techniques to assess babies born with severe combined immune deficiency (SCID) and other primary immunodeficiencies using next generation sequencing technologies as a second tier test in state newborn screening laboratories. Applicants must represent or be part of a coordinated partnership with an established state or territorial newborn screening program and research activities must occur within the high-throughput state newborn screening setting to ensure implementation of research findings. Documentation of collaborations includes letters of support, memoranda of understanding or agreement, or interagency plans. The documentation must describe the nature and extent of the relationship and be included in the appendix. Applications without documentation of established collaborations with a state or territorial newborn screening program will be considered nonresponsive and will not be submitted for review.

The purpose of this FOA is to provide additional clarifying information based on questions received from potential applicants during the Pre-Application Conference Call or as a result of direct communication with the Scientific Program Official. A summary of the "questions and answers" begins on page 29.

4. Justification for Less than Maximum Competition

N/A

5. Responsiveness

Applicants must represent or clearly describe the relationship with the participating state or territorial newborn screening program.

Proposed research activities must occur in the state public health newborn screening laboratory.

If the applicant is collaborating with the participating state or territorial newborn screening program, documentation of the collaboration must be included in the appendix.

Application must include documentation of all collaborations described in the proposal.

Documentation of the collaboration is illustrated by letters of support, memoranda of understanding or agreement, or an interagency plan that details the nature and extent of the involvement from the performing organization and outside entities. These items need to be clearly described in the proposal and included in the appendix.

Applications may not exceed any referenced page limits.

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) 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.

(Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https://eportal.nspa.nato. int/AC135Public/Docs/US%20Instructions%2 0for%20NSPA%20NCAGE.pdf System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, https://www.sam.gov/portal/SAM/#1.

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes.

The “one-time” registration process will take three to five days to complete. However, it is best to start the registration process at least two weeks prior to application submission.

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 successfully completed and active before 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.

7. Universal Identifier Requirements and System for Award Management (SAM) All applicant organizations must obtain a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements.

The DUNS number is a nine-digit number assigned by Dun and Bradstreet Information Services. An AOR should be consulted to determine the appropriate number. If the organization does not have a DUNS number, an AOR should complete the US D&B D-U-N-S Number Request Web Form or contact Dun and Bradstreet by telephone directly at 1-866-705-5711 (toll-free) to obtain one. A DUNS number will be provided immediately by telephone at no charge. Note this is an organizational number. Individual Program Directors/Principal Investigators do not need to register for a DUNS number.

Additionally, all applicant organizations must register in the System for Award Management (SAM).

Organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later. SAM is the primary registrant database for the https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://www.sam.gov/portal/SAM/%231 http://www.Grants.gov https://public.era.nih.gov/commons/public/login.do?TYPE=33554433&REALMOID=06-1edb031f-46c7-44b3-b803-60b537de74d2&GUID=&SMAUTHREASON=0&METHOD=GET&SMAGENTNAME=-SM-938PYmoLVb4VrDeXo04LZUDVDvc%2b3899ByInEAjuSUvWNIGfB2zRpWiCivYGCogG&TARGET=-SM-http%3a%2f%2fpublic%2eera%2enih%2egov%2fcommons http://www.Grants.gov http://fedgov.dnb.com/webform

Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient. Additional information about registration procedures may be found at the SAM internet site at https://www.sam.gov/index.html.

If an award is granted, the grantee organization must notify potential sub-recipients that no organization may receive a subaward under the grant unless the organization has provided its DUNS number to the grantee organization.

8. Eligible Individuals (Project Director/Principal Investigator) in Organizations/Institutions Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project 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 HHS/CDC support.

9. Cost Sharing This FOA does not require cost sharing as defined in the HHS Grants Policy Statement (http:// www.hhs.gov/ asfr/ ogapa/ aboutog/ hhsgps107.pdf).

10. Number of Applications As defined in the HHS Grants Policy Statement, (http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf), applications received in response to the same funding opportunity announcement generally are scored individually and then ranked with other applications under peer review in their order of relative programmatic, technical, or scientific merit. HHS/CDC 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.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct. However, applicant institutions can submit only one grant application with the same principal investigator.

Section IV. Application and Submission Information

1. Address to Request Application Package Applicants must download the SF424 (R&R) application package associated with this funding opportunity from www.Grants.gov.

If access to the Internet is not available or if the applicant encounters difficulty accessing the forms on-line, contact the HHS/CDC Procurement and Grants Office Technical Information Management Section (PGO TIMS) staff at (770) 488-2700 or pgotim@cdc.gov for further instructions. Hours: Monday - Friday, 7am – 4:30pm U.S. Eastern Standard Time. CDC Telecommunications for the hearing impaired or disabled is available at: TTY 1-888-232-6348.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/ 424/SF424_RR_Guide_General_VerC.pdf), 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.

The forms package associated with this FOA includes all applicable components, mandatory and optional.

Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow the instructions in the SF 424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, https://www.sam.gov/index.html http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.Grants.gov mailto:pgotim@cdc.gov additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, additional data required by the agency for a complete application. While these are not identical to the PHS398 application form pages, the PHS398 reference is used to distinguish these additional data requirements from the data collected in the SF424 (R&R) components. A complete application to CDC will include SF424 (R&R) and PHS398 components.

3. Letter of Intent Due Date for Letter of Intent: 03/11/2015

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 CIO staff to estimate the potential review workload and plan the review.

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

Name of the Applicant 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:

Jane Suen, DrPH

Scientific Research Official for the National Center for Environmental Health, ATSDR, and NCIPC

Centers for Disease Control and Prevention (CDC)

4770 Buford Hwy, NE Mailstop F-63

Atlanta, GA 30341 Telephone: 770-488-4281 Email: JXS8@cdc.gov

4. Required and Optional Components A complete application has many components, both required and optional. The forms package associated with this FOA in Grants.gov includes all applicable components for this FOA, required and optional.

5. PHS 398 Research Plan Component The SF424 (R&R) Application Guide includes instructions for applicants to complete a PHS 398 Research Plan that consists of 16 components. Not all 16 components of the Research Plan apply to all Funding Opportunity Announcements (FOAs). Specifically, some of the following 16 components are for Resubmissions or Revisions only. See Part I, Section 5.5 of the SF 424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf) for additional information. Please attach applicable sections of the following Research Plan components as directed in Part 2, Section 1 (Funding Opportunity Announcement Description).

Follow the page limits stated in the SF 424 unless otherwise specified in the FOA. As applicable to and specified in the FOA, the application should include the bolded headers in this section and should address activities to be conducted over the course of the entire project, including but not limited to:

mailto:SFN8@cdc.gov

1. Introduction to Application (for Resubmission and Revision ONLY) - provide a clear description about the purpose of the proposed research and how it addresses the specific requirements of the FOA.

2. Specific Aims – state the problem the proposed research addresses and how it will result in public health impact and improvements in population health.

3. Research Strategy – the research strategy should be organized under 3 headings: Significance, Innovation and Approach. Describe the proposed research plan, including staffing and timeline.

4. Inclusion Enrollment Report (Renewal and Revision applications ONLY)

5. Progress Report Publication List (for Continuation ONLY)

Human Subjects Section

6. Protection of Human Subjects

7. Inclusion of Women and Minorities

8. Targeted/Planned Enrollment Table (for New Application ONLY)

9. Inclusion of Children

Other Research Plan Sections

10. Vertebrate Animals

11. Select Agent Research

12. Multiple PD/PI Leadership Plan.

13. Consortium/Contractual Arrangements

14. Letters of Support

15. Resource Sharing Plan(s)

16. Appendix

Component 4 (Inclusion Enrollment Report) applies only to Renewal and Revision applications for clinical research. Clinical research is that which is conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, and (d) development of new technologies). Follow the page limits in the SF 424 unless otherwise specified in the FOA.

All instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf) must be followed along with any additional instructions provided in the FOA.

6. Appendix Do not use the appendix to circumvent page limits. A maximum of 10 PDF documents are allowed in the appendix. Additionally, up to 3 publications may be included that are not publically available. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

7. Page Limitations All page limitations described in this individual FOA must be followed. For this specific FOA, the Research Strategy component of the Research Plan narrative is limited to 25 pages. Supporting materials for the Research Plan narrative included as appendices may not exceed 10 PDF files with a maximum of 60 pages for all appendices.

8. Format for Attachments Designed to maximize system-conducted validations, multiple separate attachments are required for a complete application. When the application is received by the agency, all submitted forms and all separate attachments are combined into a single document that is used by peer reviewers and agency staff. Applicants should ensure that all attachments are uploaded to the system.

CDC requires all text attachments to the Adobe application forms be submitted as PDFs and that all text attachments conform to the agency-specific formatting requirements noted in the SF424 (R&R) Application Guide (Part I, Section 2) (http://grants.nih.gov/ grants/funding/424/ SF424_RR_Guide_General_VerC.pdf).

9. Submission Dates & Times Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov (http://www.grants.gov), the online portal to find and apply for grants across all Federal agencies. The eRA Commons systems retrieve the application from Grants.gov and check the application against CDC business rules. If no errors are found, the application will be assembled in the eRA Commons for viewing by the applicant before moving on for further CDC processing.

If errors are found, the applicant will be notified in the eRA Commons. They must make required changes to the local copy of their application and submit again through Grants.gov.

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

Once you can see your application in the Commons, be sure to review it carefully as this is what the reviewer will see. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons (http:// grants.nih. gov/grants /guide/url_redirect .htm? id=11123).

Information on the submission process is provided in the SF424 (R&R) Application Guide.

Note: HHS/CDC grant submission procedures do not provide a period of time beyond the grant application due date to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e. error correction window).

The application package is not complete until it has passed the Grants.gov/eRA Commons validation process. This process and email notifications of receipt, validation or rejection may take two (2) business days.

Applicants are strongly encouraged to allocate additional time prior to the submission deadline to submit their applications and to correct errors identified in the validation process. Applicants are encouraged also to check the status of their application submission to determine if the application packages are complete and error-free. Applicants who encounter system errors when submitting their applications must attempt to resolve them by contacting the Grants.gov Contact Center (1-800-518-4726; support@grants.gov). If the system errors cannot be resolved, applicants must contact CDC PGO TIMS at 770-488-2700; www.pgotim@cdc.gov for guidance at least 3 calendar days before the deadline date.

After submission of your application package, applicants will receive a “submission receipt” email generated by Grants.gov. Grants.gov will then generate a second e-mail message to applicants which will either validate or reject their submitted application package. This validation process may take as http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf http://grants.nih.gov/grants/guide/url_redirect.htm?id=11128 http://www.grants.gov/ http://grants.nih.gov/grants/guide/url_redirect.htm?id=11123 mailto:support@grants.gov mailto:www.pgotim@cdc.gov will either validate or reject their submitted application package. This validation process may take as long as two (2) business days. A third and final e-mail message is generated once the applicant’s application package has passed validation and the grantor has confirmed receipt of the application.

Unsuccessful Submissions:

If an application submission was unsuccessful, the applicant must:

1. Track his/her submission and verify the submission status (tracking should be done initially regardless of rejection or success).

a. If the status states “rejected,” do #2a or #2b.

2. Check his/her emails from both Grants.gov and eRA Commons for rejection notices.

a. If the deadline has passed, he/she should email the Grant Management Specialist listed in the FOA (pgotim@cdc.gov) explaining why the submission failed.

b. If there is time before the deadline, he/she should correct the problem(s) and resubmit as soon as possible.

Due Date for Applications: 04/06/2015

Electronically submitted applications must be submitted no later than 5:00 p.m., ET, on the listed application due date.

10. Intergovernmental Review (E.O. 12372)

Your application is subject to Intergovernmental Review of Federal Programs, as governed by Executive Order 12372 (http://www.archives.gov/federal-register/codification/executive-order/12372.html). This order sets up a system for state and local review of proposed federal assistance applications. You should contact your state single point of contact (SPOC) as early as possible to alert the SPOC to prospective applications, and to receive instructions on your state’s process. Click on the following link to get the current SPOC list:

http://www.whitehouse.gov/omb/grants_spoc/.

11. Funding Restrictions All HHS/CDC awards are subject to the terms and conditions, cost principles, and other requirements described in the HHS Grants Policy Statement. Pre-award costs may be allowable as an expanded authority, but only if authorized by CDC.

For more information on expanded authority and pre-award costs, go to: http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf.

12. Other Submission Requirements and Information

Application Submission Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

Applicants must complete all required registrations before the application due date. Section III.6 "Required Registrations" contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically (http://grants.nih.gov/grants/guide /url_ redirect.htm? id=11144).

Important reminders:

All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to http://www.archives.gov/federal-register/codification/executive-order/12372.html http://www.whitehouse.gov/omb/grants_spoc/ http://grants.nih.gov/grants/guide/url_redirect.htm?id=11144

Profile Component of the SF 424(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 CDC.

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…