RFA-DD-15-001 Amendment 1.pdf

Centers for Disease Control and Prevention

National Center on Birth Defects and Developmental Disabilities Extramural Research Program Office

Public Health Research on Modifiable Risk Factors for Spina Bifida

RFA-DD-15-001

Application Due Date: 02/24/2015

Public Health Research on Modifiable Risk Factors for Spina Bifida

RFA-DD-15-001

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 on Birth Defects and Developmental Disabilities Extramural Research Program Office

(NCBDDD ERPO)

National Center on Birth Defects and Developmental Disabilities (NCBDDD) Funding Opportunity Announcement (FOA) Title Public Health Research on Modifiable Risk Factors for Spina Bifida Activity Code AMENDMENT 1 made on February 3, 2015.

Appendix A "Questions from Potential Applicants and CDC Responses" added to Section VIII. Other Information.

Attachment 1 "Selected Public Health Priorities for the Identification and Confirmation of Spina Bifida Risk Factors Based on Recent CDC-Funded Studies” added to Section VIII. Other Information.

U01

Funding Opportunity Announcement Type New Funding Opportunity Announcement Number

RFA-DD-15-001

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.073 Category of Funding Activity:

Health FOA Purpose This FOA solicits applications in the form of cooperative agreements to investigate potentially modifiable risk factors for spina bifida in the presence of adequate folate (i.e. where there is established mandatory folic acid fortification or among populations for which there is individual-level data on periconceptional folic acid use), including identification of novel risk factors, identification of factors that may alter the impact of established risk factors (e.g. physical activity and obesity), and replication of previously observed associations from population-based epidemiological studies (e.g. National Birth Defects Prevention Study).

Key Dates Publication Date: To receive notification of any changes to RFA-DD-15-001, 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: 01/23/2015

Application Due Date: 02/24/2015

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: 04/01/2015

Secondary Review: 06/01/2015

Estimated Start Date: 09/01/2015

Expiration Date: 02/21/2015 Due Dates for E.O. 12372: Executive Order 12372 does not apply to this program.

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 solicits applications in the form of cooperative agreements to investigate potentially modifiable risk factors for spina bifida in the presence of adequate folate (i.e.

where there is established mandatory folic acid fortification or among populations for which there is individual-level data on periconceptional folic acid use), including identification of novel risk factors, identification of factors that may alter the impact of established risk factors (e.g. physical activity and obesity), and replication of previously observed associations from population-based epidemiological studies (e.g. National Birth Defects Prevention Study).

Mechanism of Support. Cooperative agreement Funds Available and Anticipated Number of Awards. We anticipate up to 2 awards being made under this FOA and total available funding of approximately $1,800,000 over the entire project period. Awards issued under this FOA are contingent upon availability 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 each award may also vary. The total amount awarded and the number of awards will depend upon the number, quality, duration, and cost of the applications received.

Budget and Project Period. The estimated total funding (direct and indirect) for the first year (12 month budget period) is $600,000 ($300,000 per applicant with up to 2 applicants awarded) and the estimated total funding (direct and indirect) for the entire project period is $1,800,000. The budget period is anticipated to be 09/01/2015 to 08/31/2016 and the estimated project period will run from 09/01/2015 to 08/31/2018.

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

http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIV http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIII1A

Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply. Institutions that are funded under FOA #DD13-003(Birth Defects Study to Evaluate Pregnancy exposureS, BD-STEPS) may not propose analysis of NBDPS data under this FOA #DD15-001 due to funding overlap.

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. Applications may contain more than one PI; however, the first PI listed will be the “contact PI” for all correspondence.

Number of Applications. Eligible applicant institutions may submit no more than one application.

Application Type. New Special Date(s). Not applicable 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

Section 301 and 317C of the Public Health Service Act [42 U.S.C. 241, and 247b-4 as amended].

1. Background and Purpose

Spina bifida is a condition that affects the spine and is usually apparent at birth. It is a type of neural tube defect (NTD). Although the prevalence of spina bifida has declined significantly in the United States since the implementation of mandatory fortification of enriched cereal grain products with folic acid (from 6.4 to 4.1 per 10,000 live births)[1], spina bifida still affects almost 1,500 pregnancies in the United States annually.[2] Worldwide, the March of Dimes estimates that there are over 200,000 spina bifida-affected pregnancies.[2, 3] Children born with spina bifida are at increased risk for infant mortality; although improved medical treatment has improved survival in some areas, those affected by spina bifida are at high risk for severe, lifelong disabilities, including paralysis, hydrocephalus, tethered cord, and neurological deficits.[4] Both folic acid research and the development and implementation of prevention strategies remain essential components in CDC’s public health response to spina bifida. CDC’s folic acid research and the development and implementation of strategies to prevent spina bifida build upon other CDC efforts, such as programs that monitor the birth prevalence of spina bifida and other birth defects, an activity critical to monitoring trends and identifying disparities. CDC has identified priority areas for public health research to address current gaps in knowledge for spina bifida. The purpose of this funding announcement is to address some of those gaps by investigating potentially modifiable risk factors for spina bifida in the presence of adequate folate (i.e. where there is established mandatory folic acid fortification or among populations for which there is individual-level data on periconceptional folic acid use), including identification of novel modifiable risk factors, http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIV http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIII1A http://grants.nih.gov/grants/guide/pa-files/PAR-11-022.html#SectionIV1 file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-001%20Spina%20Bifida/FOA%20DD15-001-spina%20bifida-Stuart-clean%20version-10%2030%2014.docx file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-001%20Spina%20Bifida/FOA%20DD15-001-spina%20bifida-Stuart-clean%20version-10%2030%2014.docx file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-001%20Spina%20Bifida/FOA%20DD15-001-spina%20bifida-Stuart-clean%20version-10%2030%2014.docx file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-001%20Spina%20Bifida/FOA%20DD15-001-spina%20bifida-Stuart-clean%20version-10%2030%2014.docx file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-001%20Spina%20Bifida/FOA%20DD15-001-spina%20bifida-Stuart-clean%20version-10%2030%2014.docx periconceptional folic acid use), including identification of novel modifiable risk factors, identification of factors that may alter the impact of established risk factors (e.g. physical activity and obesity), and replication of previously observed associations from population-based studies (e.g.

National Birth Defects Prevention Study).

Healthy People 2020 and other National Strategic Priorities

The National Center on Birth Defects and Developmental Disabilities (NCBDDD) of CDC within HHS is committed to achieving the health promotion and disease prevention objectives of “Healthy People 2020”. This RFA addresses “Healthy People 2020” priority area of Maternal, Infant, and Child Health, and specifically Objective MICH-28.1, “Reduce the occurrence of spina bifida”.

Public Health Impact

Each year spina bifida affects pregnancies of more than a thousand families in the U.S., and hundreds of thousands of families worldwide. Children born with spina bifida are at increased risk of death and disability, including paralysis and neurological deficits, with large lifetime medical costs.There is no known cure for spina bifida, making prevention of this defect of paramount importance.Although periconceptional folic acid use is one proven preventive strategy for spina bifida, not all cases are preventable with sufficient folic acid. Cases continue to occur in the presence of adequate folic acid intake, and therefore other risk factors remain to be identified. The results of this FOAwill aid in the development of new prevention strategies, ultimately allowing women and their healthcare providers to take action toward preventing more cases of spina bifida and maximizing the opportunity for healthy pregnancies and healthy babies.

Relevant Work

Public Health Research on Spina Bifida – A previous cooperative agreement (FOA# DD10-002) between CDC and investigators at Boston University focused on analysis of existing data to examine modifiable risk factors for spina bifida among women who did and did not have the recommended periconceptional folic acid intake for NTD prevention. This project was productive, with research published on a wide variety of topics including: periconceptional opioid analgesic use;[5] periconceptional tea consumption;[6] maternal diabetes and obesity;[7] and maternal periconceptional use of cigarettes, alcohol, and coffee.[8] National Birth Defects Prevention Study (NBDPS) The NBDPS is the largest population-based case-control study of birth defects in the U.S. Mothers of more than 30,000 babies with birth defects, including over 2,200 with spina bifida, and 10,000 babies without birth defects took part in the study. Over 150 scientific papers have been published using data from NBDPS including 65 papers that have assessed spina bifida, and although interviewing of mothers for NBDPS stopped in March 2013, analysis of the NBDPS data will continue to identify risk factors for birth defects. Web site: http://www.cdc.gov/ncbddd/birthdefects /nbdps.html.

Birth Defect Study to Evaluate Pregnancy exposureS (BD-STEPS)

BD-STEPS (FOA# DD13-003) builds upon the foundation of birth defects research from NBDPS and further examines findings and follows up on leads from NBDPS research to understand more about what causes birth defects and how to prevent them. BD-STEPS began collecting data on children born on or after January 1, 2014. Web site: http://www.cdc.gov/ncbddd/birthdefects/bd-steps file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-002%20Spina%20Bifida/FOA%20DD15-001%20DRAFT%20Research%20FOA%20_2014Oct3.docx file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-002%20Spina%20Bifida/FOA%20DD15-001%20DRAFT%20Research%20FOA%20_2014Oct3.docx file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-002%20Spina%20Bifida/FOA%20DD15-001%20DRAFT%20Research%20FOA%20_2014Oct3.docx file://cdc.gov/private/L103/ndh6/@ERPOS/SPO%20FY%202015%20PROJECTS/DD15-002%20Spina%20Bifida/FOA%20DD15-001%20DRAFT%20Research%20FOA%20_2014Oct3.docx http://www.cdc.gov/ncbddd/birthdefects/nbdps.html http://www.cdc.gov/ncbddd/birthdefects/nbdps.html http://www.cdc.gov/ncbddd/birthdefects/bd-steps.html children born on or after January 1, 2014. Web site: http://www.cdc.gov/ncbddd/birthdefects/bd-steps .html.

Treating for Two Initiative CDC’s Treating for Two: Safer Medication Use in Pregnancy Initiative aims to improve the availability and quality of data to help inform clinical decision-making for women who are pregnant or who could become pregnant. An important part of this initiative is to expand research, including both examination of medications that have not previously been studied for their use during pregnancy, and digging deeper into associations that have been observed, focusing on details of medication-taking such as dose, indication, and concomitant medication use. Web site: http://www .cdc.gov/pregnancy/meds/treatingfortwo/index.html .

This announcement is for research activities supported by CDC. For the definition of research, please see the CDC Web site at the following Internet address: http://www.cdc.gov/od/science/regs /hrpp/researchDefinition.htm

2. Approach

Awardees should utilize pre-existing surveillance data (or population-based registry data) or build on the infrastructure of an existing case-control study to assess risk factors for spina bifida in populations exposed to mandatory folic acid fortification, or populations for which there is complete information available on individual-level use of periconceptional use of folic acid. Awardees should design and conduct an analysis in which a population of pregnancies affected by spina bifida is identified and compared to a reference group of pregnancies not affected by spina bifida. This comparison population must be selected from the same source population as the spina bifida cases.

The comparison group should be a representative sample of the source population and not a convenience sample. Inclusion of pregnancies affected by spina bifida that ended in elective termination and stillbirth, in addition to live birth, is strongly encouraged.

Research should focus on 1) identification of novel risk factors; 2) identification of factors that may alter the impact of established risk factors; and/or 3) replication of previously observed associations from population-based epidemiological studies. Research on novel risk factors must focus on potentially modifiable factors which have not previously been assessed for their association with spina bifida, or for which there are few data and/or inconsistent results, but for which biological plausibility for an association exists. Confirmation of well-established risk factors for spina bifida, such as obesity, Hispanic ethnicity, low acculturation, anti-epileptic medication use, and pre-gestational diabetes, is not an acceptable aim of the proposed research. However, a more refined assessment of these risk factors, or other previously reported risk factors, is strongly encouraged.

Examples of such investigations include: 1) assessing the potential modifying effect of physical activity on the association between diabetes and/or prepregnancy obesity and spina bifida, and 2) assessing whether specific medications within a medication class (e.g. opioids) or certain doses of medication are more or less associated with spina bifida risk. Associations reported from large, population-based research studies, such as the National Birth Defects Prevention Study (NBDPS), require confirmation from other data sources. NBDPS has reported on many exposures and their association with spina bifida risk, including specific medications and occupational exposures (some selected examples are provided in Attachment 1).

Sites that are receiving funding under FOA #DD13-003 for the Birth Defects Study to Evaluate Pregnancy exposureS (BD-STEPS) are already receiving funding for analyses of http://www.cdc.gov/ncbddd/birthdefects/bd-steps.html http://www.cdc.gov/ncbddd/birthdefects/bd-steps.html http://www.cdc.gov/pregnancy/meds/treatingfortwo/index.html http://www.cdc.gov/pregnancy/meds/treatingfortwo/index.html http://www.cdc.gov/od/science/regs/hrpp/researchDefinition.htm http://www.cdc.gov/od/science/regs/hrpp/researchDefinition.htm previously-collected NBDPS data and thus may not propose analysis of NBDPS data under this FOA #DD15-001. Sites previously funded for the National Birth Defects Prevention Study (NBDPS) that are not funded under FOA #DD13-003 may propose analyses of NBDPS data under this FOA; however, they must augment this plan by either identifying other sources of data with which to replicate NBDPS findings or justify the importance of using NBDPS data for an original replication of results from other population-based studies of spina bifida risk factors.

While the FOA intent is, among other goals, to develop an assessment of policy interventions designed to reduce the incidence of diabetes, awardees, in providing an assessment, must comply with the provisions in Administrative Requirement 12, Lobbying Restrictions, which prohibits the use of federal funds “related to any activity designed to influence the enactment of legislation, appropriations, regulation, administrative action, or Executive order proposed or pending before the Congress or any state government, state legislature or local legislature or legislative body.” More information can be found in Section VI Award Administration Information regarding Administrative Requirement 12.

Objectives/Outcomes

1. Design and develop a plan for analyzing existing data A research design should be developed that includes a detailed methodology addressing 1) identification of the target population; 2) identification of data source(s); 3) identification of potentially modifiable risk factors and modifying factors of established risk factors to be assessed;

and 4) discussion of sample size with power calculations to demonstrate adequate statistical power for the proposed objectives. Analyses should include consideration of demographic factors, such as maternal age, race-ethnicity, education, and family socioeconomic status.

2. Analyze existing data A plan for analyzing the data from the identified data sources should address the type of data or information to be utilized, and include variables such as: case and control status, including some detailed clinical information; demographic factors, e.g. maternal age, race-ethnicity, education, and family socioeconomic status; maternal health information; pregnancy information, e.g., maternal diet, illnesses and medications used during pregnancy; occupational information; environmental and residential information.

3. Disseminate results of analysis A plan for disseminating study findings should be developed. The plan should include production and publication of peer-reviewed scientific manuscripts. A confidential abstract draft should be provided to CDC for each manuscript developed that was supported in part or whole by this cooperative agreement; at least 5 published peer-reviewed manuscripts at the end of the 3 year project period on risk factors for spina bifida or other papers furthering the field of spina bifida research are expected.

Target Population

The target population are women with pregnancies affected by spina bifida (cases) and pregnancies not affected by spina bifida (controls) for which information about periconceptional folic acid use can be estimated, either because the population is exposed to mandatory folic acid fortification or from individual-level data on folic acid intake those included in the study.

Collaboration/Partnerships

Collaborations across institutions are encouraged where it can strengthen the ability of the applicant to achieve the purpose of the FOA.

Evaluation/Performance Measurement

The grantees will monitor their progress toward completing their proposed activities.

Translation Plan

It is anticipated that study results will be presented at national scientific conferences and published in the peer-reviewed literature for dissemination to key stakeholders in order to facilitate translation into prevention messages. A confidential abstract draft should be provided to CDC for each manuscript developed that was supported in part or whole by this cooperative agreement; the draft should be submitted to CDC at the time the manuscript is accepted for publication. The awardees are expected to produce at least 5 published peer-reviewed manuscripts at the end of the 3 year project period on risk factors for spina bifida or other papers furthering the field of spina bifida research.

References

1. Centers for Disease Control and Prevention, Spina bifida and anencephaly before and after folic acid mandate--United States, 1995-1996 and 1999-2000. MMWR Morb Mortal Wkly Rep, 2004. 53(17):

p. 362-5.

2. Parker, S.E., et al., Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol, 2010. 88(12): p. 1008-16.

3. March of Dimes, Global Report on Birth Defects. The hidden toll of dying and disabled children.

2006, March of Dimes Birth Defects Foundation: White Plains, New York.

4. Botto, L.D., et al., Neural-tube defects. N Engl J Med, 1999. 341(20): p. 1509-19.

5. Yazdy, M.M., et al., Periconceptional use of opioids and the risk of neural tube defects. Obstet Gynecol, 2013. 122(4): p. 838-44.

6. Yazdy, M.M., et al., Maternal tea consumption during early pregnancy and the risk of spina bifida.

Birth Defects Res A Clin Mol Teratol, 2012. 94(10): p. 756-61.

7. Parker, S.E., et al., The impact of folic acid intake on the association among diabetes mellitus, obesity, and spina bifida. Am J Obstet Gynecol, 2013. 209(3): p. 239 e1-8.

8. Benedum, C.M., et al., Risk of spina bifida and maternal cigarette, alcohol, and coffee use during the first month of pregnancy. Int J Environ Res Public Health, 2013. 10(8): p. 3263-81.

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: $1,800,000

NCBDDD intends to commit up to $600,000 (including both direct and indirect costs) to fund up to 2 awards for the first 12 month budget period. We anticipate the average award to be approximately $300,000.

An applicant may request a project period of up to three (3) years. The funding amount is estimated to be $300,000 per applicant (including both direct and indirect costs) each year for the 2 nd and 3rd years of the project.

The estimated total funding (direct and indirect costs) for the entire 3 year project period is $1,800,000. An applicant may request a project period of up to 3 years.

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

Anticipated Number of Awards: 2

Applications with budget requests greater than the ceiling will be considered non-responsive and will not be reviewed.

Applications with budget requests less than the floor amount will be considered non-responsive and will not be reviewed.

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 Project Period Award Floor: $125,000 Per Project 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 http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf

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)

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)

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 Foreign Organizations: a Foreign Organization is a public or private organization, whether non-profit or for-profit, located in a country other than the United States (U.S.) and its territories that is subject to the laws of the country in which it is located, irrespective of the citizenship of project staff or place of performance. Delete when Foreign Organizations are not allowed to apply Bona Fide Agents: a Bona Fide Agent is an agency/organization identified by

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

Applicants must:

Document their ability to access data from the proposed existing data source(s) for the purposes of the proposed analyses and anticipated/expected publications.

1.

Institutions that are funded under FOA #DD13-003 (BD-STEPS) may not propose analysis of NBDPS data under this FOA #DD15-001 due to funding overlap

2.

4. Justification for Less than Maximum Competition

Not applicable

5. Responsiveness

Evidence for these criteria must be presented in Appendix A of the application, and include the following:

1) Provide either of the following:

a) Statement that the applicant institution owns the data or;

b) Letter from an authorized representative of the owner of the data stating that the applicant has access to the data for the purposes of the activities proposed in this application.

2) Statement of applicant showing they are/are not a currently funded grantee under FOA DD13-003 “Cost-Benefit of Incentive-based Smoking Cessation for Pregnant Women”

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

Incomplete applications, applications submitted after 5:00 PM on the listed application due date or non-responsive applications with budgets that exceed the ceiling or with budgets that are below the floor amount of the award will not be entered into the review process.

6. Required Registrations

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 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 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 https://www.sam.gov/index.html

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.

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, 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: 01/23/2015

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

Name of the Applicant 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 http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf

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:

Natalie J. Darling, MPH Scientific Program Official National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) and National Center on Birth Defects and Developmental Disabilities (NCBDDD) Extramural Research Program Operations and Services Centers for Disease Control and Prevention 4770 Buford Highway, NE M/S F-80 Atlanta, GA 30341 Telephone: (770) 488-5740 Email: ndarling@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:

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) mailto:ndarling@cdc.gov

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.

Research Plan The applicant’s research plan should address activities that will be conducted over the entire 3 year project period and should include the following items:

Data

- A description of the existing data that will be used in the project, including: the study methods used to collect the data; the start and end dates of data collection; and variables available in the data that will be used in analyses for this project. To the extent possible, available data should include case and control status, including some detailed clinical information; demographic factors, such as maternal age, race-ethnicity, and family socioeconomic status; maternal health information;

pregnancy information; occupational information; and environmental and residential information.

- The applicant should provide documentation of their authority to access and analyze the data.

- The applicant should demonstrate that the data were collected in areas with established mandatory folic acid, including the date when folic acid fortification began relative to their data collection dates, or that individual-level folic acid intake data are available for the study population.

Use of data exclusively or predominantly from the pre-folic acid era (i.e. prior to 1992) is not acceptable.

- A description of the population-base from which spina bifida cases were ascertained. If the study relied only on clinic- or hospital-based selection of cases, evidence must be presented that the approach resulted in a study population representative of the population of children with NTDs with respect to race-ethnicity, socioeconomic status, etc. in that geographic region.

respect to race-ethnicity, socioeconomic status, etc. in that geographic region.

- A description of how the proposed research utilizes data from existing population-based birth defects surveillance programs of children with NTDs (ICD-9 CM codes 740.0-742.0), with verification of the specific diagnoses from medical record review, autopsy, and cytogenic studies;

not based solely on codes.

- The applicant should specify whether they were able to include pregnancies affected by spina bifida that ended in elective termination and stillbirth, in addition to live birth. If stillbirths and elective terminations were not included, the applicant should describe the potential impact of this limitation on the proposed analyses.

- A description of the referent group of pregnancies not affected by spina bifida, including how it is representative of the source population and not a convenience sample.

- If proposing analysis of NBDPS data, applicant must confirm that they are not receiving funding under FOA# DD13-003 (BD-STEPS).

Analyses

- A detailed description of the proposed research methods. Describe how the proposed methods will improve comparability with other studies, and maximize the contribution the project makes to the understanding of modifiable risk and protective factors for folate-resistant NTDs. Specify exposures that will be investigated and describe how they include 1) potentially modifiable factors that have not previously been assessed for their association with spina bifida risk; 2) more refined investigation of previously-identified modifiable risk factors for spina bifida; and/or 3) replication of previously observed associations from population-based studies.

- Description of the available sample size and power calculations to demonstrate adequate statistical power for the proposed analyses.

- A description of how the proposed analyses will incorporate consideration of demographic factors, such as maternal age, race-ethnicity, education, and family socioeconomic status.

- Discuss how the data will be analyzed and by whom.

- A description of how the applicant will publish at least 5 peer-reviewed manuscripts by the end of the 3-year project period on risk factors for spina bifida or other papers furthering the field of spina bifida research.

Management

- A timeline for obtaining IRB approval for the proposed research.

- A proposed timeline of activities over the three year project period. The timeline should detail objectives, measurable steps for project implementation, completion, publications, and presentations and dates by which those objectives will be met.

- Letters of support from potential partners describing commitment of the organization to the project, any specified limits to collaboration, and if applicable, terms of access to data.

- A description of the research team’s experience with similar research projects. Evidence of such experience should be provided in the form of publications and/or reports within the last five years.

- A description of how a collaboration with scientific collaborators at CDC will be established.

6. Appendix

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 30 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.