rfa-dd-15-004amend1publication.pdf

Centers for Disease Control and Prevention

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

Stillbirth Risk Factor Pilot Project Centers for Birth Defects Research and Prevention (CBDRPs)

RFA-DD-15-004

Application Due Date: 03/20/2015

Stillbirth Risk Factor Pilot Project Centers for Birth Defects Research and Prevention (CBDRPs)

RFA-DD-15-004

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 Stillbirth Risk Factor Pilot Project Centers for Birth Defects Research and Prevention (CBDRPs) Activity Code Amendment 1 made on March 2, 2015.

Administrative Requirements (AR) and associated URLs added to Section VI. Award Administration Information, 2. CDC Administrative Requirements Appendix A "Questions from Potential Applicants and CDC Responses" added to Section VIII.

Other Information

U01

Funding Opportunity Announcement Type New Funding Opportunity Announcement Number

RFA-DD-15-004

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

Health FOA Purpose The purpose of this supplemental FOA is to use the infrastructure of the Centers for Birth Defects Research and Prevention (CBDRPs) birth defects research program to better understand the preventable causes of stillbirths with and without major birth defects.

Key Dates Publication Date: To receive notification of any changes to RFA-DD-15-004, 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: 02/20/2015

Application Due Date: 03/20/2015

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).

http://www.grants.gov

Scientific Merit Review: 05/01/2015

Secondary Review: 06/01/2015

Estimated Start Date: 09/01/2015

Expiration Date: 04/01/2015 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 N/A

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority

This program is authorized under Sections 301 and 317C of the Public Health Service Act [42 U.S.C. 241, and 247b-4 as amended].

1. Background and Purpose

Birth defects affect about 1 in 33 pregnancies and account for one in five infant deaths and contribute substantially to childhood morbidity and long-term disability. Currently, the causes of about two-thirds of all birth defects are unknown. Identifying risk factors for birth defects can provide valuable information to pregnant women and their healthcare providers to aid in making treatment decisions. Additionally, in the United States, there are about 26,000 stillbirths (pregnancy loss at 20 or more weeks of gestation) each year, nearly equal to the number of infant deaths.

Significant racial disparities exist in the occurrence of stillbirths, with non-Hispanic Black women at much higher risk of having a stillbirth than non-Hispanic White women. Older mothers over the age of 35 are also at greater risk for stillbirths. Improved understanding of the causes of stillbirths will inform public health prevention efforts.

CDC coordinates a birth defects research program entitled Centers for Birth Defects Research and Prevention (CBDRPs). Under the CBDRP program, CDC coordinated a former case-control research project entitled the National Birth Defects Prevention Study (NBDPS) and a current CBDRP project entitled the Birth Defects Study to Explore Pregnancy exposureS (BD-STEPS) to investigate potential causes of birth defects. The current BD-STEPS project includes fetuses/infants with at least one of the 17 eligible birth defects, regardless of the pregnancy outcome. Mothers of cases (those with an eligible defect) and mothers of controls (random sample of liveborn infants http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf cases (those with an eligible defect) and mothers of controls (random sample of liveborn infants without a birth defect) are interviewed between 6 weeks and 18 months after their estimated date of delivery (EDD) about a wide range of exposures just before and during pregnancy, including medical conditions and medications as well as questions on demographics and pregnancy history.

BD-STEPS includes stillbirths that have one of the 17 eligible birth defects, but does not currently include any stillbirths without major birth defects. However, the infrastructure of BD-STEPS provides an opportunity to explore risk factors for stillbirths without birth defects. Additionally, there are a few birth defects surveillance programs that have leveraged their existing infrastructure and expanded it to include surveillance of all stillbirths, including those with and without major birth defects.

Purpose The overall purpose of FOA #DD13-003(BD-STEPS) is to identify modifiable maternal exposures in early pregnancy that may increase the risk for having a pregnancy affected by certain major, structural birth defects. The purpose of this supplemental FOA is to expand the use of the infrastructure of the Centers for Birth Defects Research and Prevention (CBDRPs) birth defects research program to pilot the identification of modifiable exposures that may increase the risk of stillbirths with and without major birth defects. Key objectives include: 1) conducting a pilot study of stillbirths without major birth defects within the CBDRPs, and 2) analyzing previously collected data from CBDRP on stillbirths with major birth defects. CDC’s mission is “to promote health and quality of life by preventing and controlling disease, injury, and disability.” This program is most closely aligned with CDC’s Health Protection Goal of “Healthy People in Every Stage of Life.”

Quantifiable and measurable outcomes will be measured against the GPRA performance goal to find causes and risk factors for birth defects in order to develop prevention strategies.

Healthy People 2020 and other National Strategic Priorities

This program addresses the “Healthy People 2020” objective to reduce the rate of infant mortality related to birth defects and due to congenital heart defects (MICH-1.6 and MICH-1.7) and the objective to reduce the prevalence of spina bifida (MICH-28.2).

Measurable outcomes of the program will be in alignment with the first performance goal for the National Center on Birth Defects and Developmental Disabilities: Prevent major birth defects attributable to maternal risk factors.

Public Health Impact

Each year, tens of thousands of families are affected by pregnancies ending in stillbirths. Stillbirths are an under-evaluated and under-reported public health issue. There is little information on the causes of stillbirths and what impact having a stillbirth will have on future pregnancies. By adding stillbirths without birth defects and analyzing the data in the CBDRPs research program, we hope to address two key outcomes: 1) identify possible modifiable risk factors for stillbirths without birth defects, and 2) identify differences in risk factors for specific birth defects by pregnancy outcome (live birth vs. stillbirth), with dissemination of the results to the medical community, maternal and child health researchers, and to the public. Such information can be used to better inform both the medical community and the public about how to reduce the risk or prevent stillbirths.

Relevant Work

Under the CBDRP birth defects research program, CDC funded the National Birth Defects Prevention Study (NBDPS) beginning in 1997 and the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS) beginning in 2013. The NBDPS has generated over 200 peer reviewed publications with additional manuscripts projected over the coming years. BD-STEPS will build upon the foundation of the NBDPS, but will be a more targeted birth defects research project.

2. Approach

In collaboration with CDC and all funded sites, awardees will expand their current activities under FOA #DD13-003: BD-STEPS to include stillbirths without defects. This includes defining the surveillance area, determining case definition, describing case identification including clinical review, inviting identified potential participants to complete maternal interviews (conducted under a CDC funded contract), and analysis of resulting data. Awardees will collaborate with CDC staff on the design of an online supplemental questionnaire for mothers of stillbirths (including those with a BD-STEPS eligible defect and those with no major birth defects). All proposed activities will be coordinated with all stillbirth-specific pilot sites in BD-STEPS participating in this pilot, and support using identical methods and protocols whenever possible.

Objectives/Outcomes

1) Develop and implement a plan for timely recruitment of mothers of stillbirths without major birth defects and to assess risk factors for stillbirths based on maternal interview.

2) Analyze the stillbirths and control data from the NBDPS and BD-STEPS birth defects research projects, and for specific defects compare risk factors by pregnancy outcome (e.g., live birth, stillbirth, etc).

3) Disseminate the pilot project results as published manuscripts in peer-reviewed scientific journals.

Target Population

The target population is families affected by stillbirths and healthcare providers.

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 submitted for publication.

OMB/PRA is expected to apply.

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: $1,200,000

Approximately $200,000-$400,000 in FY15 with $600,000 - $1,200,000 total for the project period.

1 – 2 awards are anticipated.

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

Maximum - $300,000. This ceiling is for the first 12-month budget period and represents total cost, which would include indirect costs.

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

Minimum – $100,000. This floor is for the first 12-month budget period and represents total cost, which would include indirect costs 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: $300,000 Per Project Period Award Floor: $100,000 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 http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf

1. Eligible Applicants Eligibility Category: State governments

Public and State controlled institutions of higher education Private institutions of higher education Others (see text field entitled "Additional Information on Eligibility" for clarification)

Other:

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 not include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Special Eligibility Requirements

This competitive FOA supplement is limited to the 6 currently funded grantees for the Centers for Birth Defects Research and Prevention (CBDRP) under exisiting FOA DD-13-003 that have access to both NBDPS and BD-STEPS data. The 6 currently funded grantees are: Arkansas Children's Hospital Research Institute;

University of Iowa; Massachusetts Department of Public Health; University of North Carolina - Chapel Hill;

New York State Department of Health/HRI; and Stanford University. The FOA is limited to these organizations because the activities will directly rely on the funded CBDRPs infrastructure and databases

The currently funded grantees are Higher Education Institutions, State Governments, or Bona Fide Agents of State Governments.

4. Justification for Less than Maximum Competition

DD-15-004 is a competitive supplement to the existing FOA (DD-13-003) which limits funding to 6 grantees that have access to both NBDPS and BD-STEPS data for the Centers for Birth Defects Research and Prevention (CBDRP) . The 6 currently funded grantees are: Arkansas Children's Hospital Research Institute; University of Iowa; Massachusetts Department of Public Health; University of North Carolina - Chapel Hill; New York State Department of Health/HRI; and Stanford University. Competition is limited to these organizations because the activities will directly rely on the funded CBDRPs infrastructure and databases. The currently funded grantees are Higher Education Institutions, State Governments, or Bona Fide Agents of State Governments. CDC has had research cooperative agreements with most of these organizations since 1995.

CDC coordinates a birth defects research program entitled Centers for Birth Defects Research and Prevention (CBDRPs). Under the CBDRP program, CDC coordinated a former case-control research project entitled the National Birth Defects Prevention Study (NBDPS) and a current CBDRP project entitled the

Birth Defects Study to Explore Pregnancy exposureS (BD-STEPS) to investigate potential causes of birth defects. The current BD-STEPS project includes fetuses/infants with at least one of the 17 eligible birth defects, regardless of the pregnancy outcome. Mothers of cases (those with an eligible defect) and mothers of controls (random sample of live born infants without a birth defect) are interviewed between 6 weeks and 18 months after their estimated date of delivery (EDD) about a wide range of exposures just before and during pregnancy, including medical conditions and medications as well as questions on demographics and pregnancy history. BD-STEPS includes stillbirths that have one of the 17 eligible birth defects, but does not currently include any stillbirths without major birth defects. However, the infrastructure of BD-STEPS provides an opportunity to explore risk factors for stillbirths without birth defects. Additionally, there are a few birth defects surveillance programs that have leveraged their existing infrastructure and expanded it to include surveillance of all stillbirths, including those with and without major birth defects.

The CBDRP project is the largest birth defects case-control study in the United States. No other organizations in the US would be able to conduct the FOA DD-15-004 planned stillbirth project activities.

5. Responsiveness

N/A

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 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 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 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.

Only one application per institution (normally identified by having a unique DUNS number) is allowed.

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.

HHS/CDC will not accept any application that is essentially the same as one already reviewed.

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 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

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: 02/20/2015

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 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 electronically to:

Natalie J. Darling, MPH National Center for Chronic Disease and Health Promotion and 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

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)

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 project period and should include the following items:

1) Demonstrate existing capacity to conduct basic surveillance for all stillbirths to be included in this pilot research. NOTE: funding under this cooperative agreement can be used to enhance existing surveillance (e.g., timeliness) but should not be used to support core surveillance activities.

2) Using the infrastructure of BD-STEPS, propose a specific study to assess risks for the occurrence of stillbirths without defects.

3) Develop and describe analytic plans for analysis of previously collected data on stillbirths with major birth defects. For example, consider use of stillbirths without birth defects as a “control” for stillbirths with major birth defects instead of relying on use of the existing controls in BD-STEPS which are all live born infants with no major birth defects. As another example, propose a specific study to assess risk factors for a birth defect stratified by pregnancy outcome to determine if there are differences.

4) Demonstrate an ability to conduct surveillance of stillbirths occurring at 20 or more weeks of gestation Describe the case definition of stillbirth to be universally applied, describe what standard approach for assigning gestational age will be used and specify the specific clinical criteria used for assessing pregnancy outcome (stillbirth vs. termination vs. live birth). In an Appendix, provide the number of stillbirths for calendar year 2010 – present statewide and in the geographic area for the BD-STEPS source population. Include any available information on sub-populations of interest, such as by race, ethnicity, or maternal age.

5) Define a geographic region to include a population-based sample of mothers of stillbirths without major birth defects in BD-STEPS. The region should be sufficient to identify approximately 75-100 stillbirths per year with no major birth defects and no chromosomal abnormalities. The selected stillbirths can be limited to a high risk population (e.g., African Americans) or one etiological group, but still needs to be population-based and should exclude stillbirths with any major birth defects (i.e. BD-STEPS eligible defects and all other major birth defects following the Metropolitan Atlanta Congenital Defects Program definitions for major birth defects).

6) Propose a timeline and plan for modifying the existing BD-STEPS protocol for the inclusion of stillbirths without birth defects

7) Describe how the systematic clinical review and classification of each stillbirth will be completed. Develop and describe how the relevant clinical data on stillbirths without major birth defects will be included in the clinical database, including relevant maternal clinical information, pregnancy complications, post mortem autopsy, and placental histopathology information.

8) Propose a plan for identifying contact information for mothers within the timeframe necessary such that they can send the mothers introduction packets and refer them to the CDC-funded interview contractor as soon as possible once the mother is 6 weeks post-EDD and have all maternal interviews completed within 18 months after the EDD.

9) Describe the analytic plan for the newly collected data on all stillbirths. Highlight how this data may improve the understanding of the occurrence of stillbirths and prevention opportunities.

10) Propose specific analyses of previously collected data on stillbirths with birth defects in NBDPS to assess:

i. Differences in risk factors for specific birth defects by pregnancy

i. Differences in risk factors for specific birth defects by pregnancy outcome (live birth vs. stillbirth)

ii. Specific risk factors associated with having a stillbirth outcome among all case-infants included in NBDPS.

iii. Impact of using stillbirths without birth defects as a control group for stillbirths with major birth defects.

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 35 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 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/ 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 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: 03/20/2015

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)

This initiative is not subject to intergovernmental review (http:// www. whitehouse.gov/ omb/ grants_spoc).

http://grants.nih.gov/grants/guide/url_redirect.htm?id=11123 mailto:support@grants.gov mailto:www.pgotim@cdc.gov 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.

Award funds cannot be used to conduct basic birth defects or stillbirth surveillance activities.

Applicants are advised that any activities involving standard information collection (i.e., surveys, questionnaires, data requests, etc.) from 10 or more non-federal individuals/entities are subject to Paperwork Reduction Act (PRA) requirements and may require the CDC to coordinate an OMB/PRA approval request.

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 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 Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

If the applicant has an FWA number, enter the 8-digit number. Do not enter the letters “FWA” before the number. If a Project/Performance Site is engaged in research involving human subjects, the applicant organization is responsible for ensuring that the Project/Performance Site operates under and appropriate Federal Wide Assurance for the protection of human subjects and complies with 45 CFR Part 46 and other CDC human subject related policies described in Part II of the SF 424 (R&R) Application Guide and in the HHS Grants Policy Statement.

See more resources to avoid common errors and submitting, tracking, and viewing applications: http:// grants.nih. gov/grants/ Electronic Receipt /avoiding _errors.htm or http:// grants. nih.gov/grants/ Electronic Receipt/submit _app.htm

Upon receipt, applications will be evaluated for completeness by the CDC Procurement and Grants Office (PGO) and responsiveness by PGO and the Center, Institute or Office of the CDC. Applications that are incomplete and/or nonresponsive will not be reviewed.

Section V. Application Review Information

1. Criteria http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://grants.nih.gov/grants/guide/url_redirect.htm?id=11144 http://grants.nih.gov/grants/ElectronicReceipt/avoiding_errors.htm http://grants.nih.gov/grants/ElectronicReceipt/avoiding_errors.htm http://grants.nih.gov/grants/ElectronicReceipt/submit_app.htm http://grants.nih.gov/grants/ElectronicReceipt/submit_app.htm

1. Criteria Only the review criteria described below will be considered in the review process. As part of the CDC mission (http:// www.cdc.gov/ about/ organization/ mission.htm), all applications submitted to the CDC in support of public health research are evaluated for scientific and technical merit through the CDC peer review system.

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

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the project? Have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

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

If the project involves clinical research, are there plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

http://www.cdc.gov/about/organization/mission.htm

Has the applicant documented their existing capacity to conduct basic surveillance for all stillbirths?

Has the applicant documented how they will meet the case ascertainment sensitivity and timeliness requirements of the project (i.e. identified contact information within 6 weeks post-EDD)?

Has the applicant provided evaluation metrics for the project that are SMART (specific, measurable, achievable, realistic, time-phased)?

Has the applicant demonstrated analysis and utilization of stillbirth surveillance data?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Is there sufficient existing support for the birth defects surveillance system to warrant timely and complete ascertainment of cases?

Is there documented collaboration between the State health department and the grantee (if other than State Health Department)?

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

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

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the HHS/CDC Requirements under AR-1 Human Subjects Requirements

(http://www.cdc.gov/od/pgo/funding/grants/additional_req.shtm#ar1).

If your proposed research involves the use of human data and/or biological specimens, you must provide a justification for your claim that no human subjects are involved in the Protection of Human…