dd13-003 foa final amendment 1 01.28.13.docx

Amendment I made 1.29.13:

Section 1. Funding Opportunity Announcement; Timeline; Phase 3; correction (Months 55-60)

Attachment 1 Questions from potential applicants with answers by CDC were added.

Table of Contents SUBMISSION CHECKLIST TO ACCOMPANY FIRST SUBMISSION OF RESEARCH FUNDING OPPORTUNITY ANNOUNCEMENT (FOA)

Part 1. Overview Information

Funding Opportunity Announcement Type

New

Key Dates Publication Date

To receive notification of any changes to RFA-DD-13-003, 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.

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).

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. The purpose of this FOA 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.

· Mechanism of Support. Cooperative agreement.

· Funds Available and Anticipated Number of Awards. We anticipate 6 – 9 awards being made under this FOA and total available funding of approximately $25,750,000 over the entire project period.

Awards issued under this FOA are contingent upon availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed research will vary from application to application, it is also anticipated that the size and duration of 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 $1,750,000 and the estimated total funding (direct and indirect) for the entire project period is $25,750,000. The estimated total (direct and indirect) funding amount for Years 2 – 5 is estimated to be $6,000,000 per year.

The budget period is anticipated to be 8/1/2013 – 7/31/2014 and the project period is anticipated to be 8/1/2013 – 7/31/2018.

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

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

· 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, and the preference would be for each grantee to have a Co-Principal Investigator; however, the first PI listed will be the “contact PI” for all correspondence.

· Number of Applications. Eligible applicant institutions may submit more than one application, provided that each application is scientifically distinct.

· 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 Announcement 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 The National Center on Birth Defects and Developmental Disabilities (NCBDDD), Division of Birth Defects and Developmental Disabilities (DBDDD), seeks to fund a collaborative project for a multi-site case control study of a select number of major birth defects.

Birth defects affect about three percent of all births in the United States and are a leading cause of infant mortality, morbidity, and healthcare costs. Birth defects account for one in five infant deaths and contribute substantially to childhood morbidity and long-term disability. Although several human teratogens and genetic factors have been identified, the causes of two-thirds of birth defects remain unknown. It is important to study specific birth defects individually, because the etiology of specific birth defects may differ substantially. Because individual types of birth defects are relatively rare, it has been difficult in the past to conduct a study large enough to provide the necessary power to assess risk factors for specific defects.

In 1996, Congress appropriated funds to initiate some of the activities described in the Birth Defects Prevention Act of 1998, including the funding of the Centers for Birth Defects Research and Prevention (CBDRP). Since FY 1996, cooperative agreements have been awarded to 9 different states. The primary collaborative activity of this project has been a multi-site case-control study called the National Birth Defects Prevention Study (NBDPS), which relies on data from the existing birth defects surveillance registries in the CBDRP.

The NBDPS has been a collaborative effort between CDC’s NCBDDD and the funded grantees. For the past 16 years, the NBDPS has provided a unique and unprecedented opportunity to assess a variety of exposures for their potential association with specific birth defects. Over 130 publications in peer-reviewed journals have reported data from the NBDPS, and results from NBDPS analyses have also been disseminated through conference proceedings and coverage by the popular press. A few highlights of these findings are described here: (1) The relationships between obesity and diabetes and specific birth defects have been elucidated by using data from the NBDPS; (2) Results from the NBDPS analysis assessing selective serotonin reuptake inhibitors (SSRIs) and specific birth defects contributed important information for decision-making when treating pregnant women with depression; (3) Data from the NBDPS have also been used to confirm previous observations of an association between the use of opioid analgesics and spina bifida and heart defects, as well as the association between maternal smoking and orofacial clefts; and (4) Gastroschisis, a defect with increasing prevalence that is strongly associated with young maternal age, was found to be associated with report of genito-urinary infections early in pregnancy.

The research experience from NBDPS also demonstrated several areas in which public health birth defects research could benefit from further study. As an example, although the association between diabetes, obesity and specific birth defects was observed in the NBDPS, it is not clear whether body fat distribution or increasing physical activity might impact the association of obesity and diabetes on birth defects. Evaluating this relationship is an important next step if targeted and appropriate public health recommendations for maximum public health impact need to be made. For studies assessing medications, NBDPS experience demonstrates the importance of documenting the indication for which the medication was taken (e.g. fever vs. pain for acetaminophen) and the dose that was consumed (e.g. SSRIs); these data were not available from the NBDPS.

This funding opportunity announcement will support CBDRP’s Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS). The objective of 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 focused on exposures amenable to future prevention efforts. The BD-STEPS will use the NBDPS as a foundation from which to innovate. BD-STEPS will employ innovative questions to target the pregnancy exposures with the most potential for use in birth defects prevention activities. By including multiple study sites BD-STEPS will aim for a study population that is representative of the US population with regards to the racial/ethnic composition of the study regions. BD-STEPS will assess how representative the study population is of the US population based on available demographics.

The BD-STEPS will focus on a smaller number of birth defects categories than the NBDPS. Selection criteria include: severity (major birth defects that are associated with disabilities, comorbidities and high health care costs), prevalence (focusing on defects that are more common), consistent ascertainment (enabling us to pool our data across the various sites) and previous findings that warrant further research. The defect categories include: spina bifida, anophthalmia and microphthalmia, anotia and microtia, eight critical congenital heart defects, cleft lip with or without cleft palate, cleft palate alone, esophageal atresia, transverse limb deficiency, diaphragmatic hernia, and gastroschisis. Examples of defect categories that were included in NBDPS that will not be included in BD-STEPS are anencephaly, and hypospadias. Population-based ascertainment of pregnancies affected by anencephaly is difficult because of the high number of these pregnancies that end in fetal deaths or termination. The NBDPS included 2nd and 3rd degree hypospadias, as 1st degree hypospadias is a more minor defect. This distinction proved difficult to implement in practice because information on the degree of hypospadias was often difficult to obtain prior to corrective surgery, which typically occurs many months after an infant’s birth.

The BD-STEPS will focus on certain key areas:

a. Chronic maternal medical conditions: Certain chronic conditions are increasingly common among women of childbearing age, and therefore also among pregnant women. In the BD-STEPS, we will introduce innovative questions to the maternal interview on asthma, autoimmune disease, and thyroid disease. As the medical field is advancing, women survive severe illness and become pregnant after surviving cancer or transplants. BD-STEPS will explore these exposures and the medications that women take for these conditions. Mental conditions including depression, anxiety, stress, and insomnia have the potential to impact pregnancy through manifestations of the condition, the exposures potentially increased as a consequence of the condition (e.g. smoking or alcohol use), and medications taken to control the condition. The BD-STEPS maternal interview will capture this information and allow better characterization of the birth defects risk associated with these conditions and any modifying factors that might reduce the risk.

b. Diabetes, obesity and physical activity: The United States is in the midst of an obesity epidemic. Obesity has been consistently associated with an increased risk for certain birth defects. Diabetes, which is also an increasingly common condition among pregnant women, has demonstrated strong, consistent associations with many major birth defects. Physical activity is a means of reducing obesity and potentially for controlling diabetes. However, some studies have reported a positive association between occupational physical activity during pregnancy and certain birth defects; other studies have reported protective associations between recreational physical activity during pregnancy and certain birth defects. Regarding obesity, it is not clear whether body fat distribution or increasing physical activity might impact the association of obesity and birth defects. The BD-STEPS will allow collection of information on these factors, and building on the existing data from the NBDPS, will have more power than any previous study to assess the interrelation of these factors, an important next step if we want to develop effective public health interventions. The BD-STEPS will also include innovative questions allowing us to explore whether losing weight before getting pregnant negates some of the risk for birth defects by asking about heaviest weight in the past five years, and weight loss strategies used (e.g. bariatric surgery, dieting).

c. Infertility: Infertility treatments have advanced substantially in the recent past and fertility treatments are an increasingly prevalent periconceptional exposure. Associations between fertility treatments and specific birth defects were observed in NBDPS data, as well as data from other studies. It has been difficult to assess whether a specific treatment, underlying infertility, or a combination may lead to the observed increase in risk for birth defects. The BD-STEPS will allow assessment of specific types of current and new procedures by building on data collected in the NBDPS.

d. Medications: Approximately 50% of pregnant women take at least one prescription medication during the first trimester, and even more report the use of over-the-counter medications. Medications have the potential to act as strong teratogens, as evidenced by thalidomide and isotretinoin. New medication products are constantly being introduced to the market, but the randomized-controlled trials that test drug safety and efficacy typically exclude pregnant women. In addition, some medications are used for an expanded list of indications over time which can increase the likelihood of exposure, such as the use of some antiepileptic medications for migraines, a much more common condition in reproductive aged women. Increases in chronic disease among pregnant women translate to increases in long term exposure to maintenance medications to control their conditions, and data are needed to inform the public of the risk/benefit assessment of continuing to take a medication during pregnancy. The BD-STEPS will expand on the previous NBDPS medications work by collecting information on the condition for which the medication was taken (e.g. whether topiramate, an antiepileptic, is being used to control seizures, manage migraines, or assist with weight loss), and the dose that was consumed (e.g. for clomiphene citrate whether it was 50, 100, or 150 mg), data which were not been collected by the NBDPS.

In addition to these four focus areas, questions will also be asked on exposures with promising prevention potential such as genitourinary infections, fever, maternal occupation, and dental procedures, as well as important potential confounders including: family history, pregnancy history, smoking, alcohol use, race/ethnicity, education level, and insurance status. In addition to using a computer-assisted questionnaire that will be administered by a central interviewing facility, we will introduce additional innovation to BD-STEPS through the use of targeted on-line questionnaire modules to obtain more detailed information from women who report certain exposures. And for some of the exposures that are recorded well in medical records, such as infertility treatment or chronic medications or conditions we will seek to obtain consent to access medical records in order to potentially allow validation of the information reported in the maternal interview.

Genetic technology has developed rapidly and collection of saliva samples instead of buccal brushes, which were used in the NBDPS, will provide higher quality and quantity DNA that is better suited to these new technologies. Along with collection of residual newborn bloodspots, the BD-STEPS will be able to complete higher throughput genetic and epigenetic analyses, enhancing the potential for gene-environment interaction studies.

Purpose The purpose of this FOA 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. 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 Birth defects account for one in five infant deaths and contribute substantially to childhood morbidity and long-term disability. Currently, two-thirds of the causes of 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.

Relevant Work CDC funded the National Birth Defects Prevention Study beginning in 1997, the predecessor birth defects case-control research project of this FOA for BD-STEPS. The NBDPS has generated over 130 peer reviewed publications with additional manuscripts projected over the coming years. The BD-STEPS will build upon the foundation of the NBDPS, but will be a more targeted birth defects research project. In order to perpetuate public health research in birth defects, we need to establish a research infrastructure and work force that understand the challenges and opportunities of working in the field of maternal and child health and especially birth defects epidemiology. Through the BD-STEPS, we will establish and encourage birth defects research opportunities for young public health professionals at the grantee sites.

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 Awardee Activities Awardees will complete activities in the following project areas: 1) project management; 2) data collection; 3) data reporting; 4) collaboration; 5) dissemination of information; 6) training and mentoring of junior researchers; and 7) progress reports. Specifically, awardees will complete the following activities.

Project management Awardees will develop a management and staffing implementation plan for the proposed program. This plan will include the provision of evidence of legal authority to access data needed to accomplish the activities required by this FOA and the awardee’s application, including HIPAA and IRB requirements. The awardee will also provide evidence of legal authority to share identifiable, individual-level contact information with CDC and its contractors and individual-level data without names and addresses with other awardees of this cooperative agreement to create a pooled analytic database. If allowed by state law, the awardee’s local IRBs will defer to a central study IRB consistent with current recommendations (Menikoff J. The paradoxical problem with multiple-IRB review. N Engl J Med 2010;363:1591-3). The central IRB will be held by the CDC IRB. If not allowable, as evidenced by appropriate documentation, a local IRB will be maintained in addition to the central IRB. For joint academic/state applications, the awardee will include documentation of a planned meaningful collaboration between the state health department and the academic center.

Data collection The grantees will use data from existing, state-funded, population-based, birth defects surveillance systems to identify all cases (either live born, stillborn, or induced abortions) with any of the proposed 17 eligible birth defects (Table 1) and conduct clinical review for case confirmation. Additional information needed to determine case eligibility or classification will be abstracted from hospital records or vital records by the grantee. For births between 1/1/2014 – 12/31/2016, the grantees will select a random sample of live births without major birth defects from the same source population as the cases to serve as the comparison group. This random sample will include approximately 75-100 births for each study year at each study site. Awardees will describe the existing birth defects surveillance system, its attributes, its funding, and the geographical area the source population will encompass. Funds from this FOA cannot be used to support the core birth defects surveillance system, but can be used to enhance the system (e.g., inclusion of prenatally diagnosed cases, improved timeliness). The identified source population for the study should include between 30,000-80,000 births per year. The grantees will be required to follow the mutually agreed upon protocol for data collection. A draft protocol for the BD-STEPS will be provided on the NCBDDD website http://www.cdc.gov/ncbddd/birthdefects/foa.html. This protocol will be finalized by CDC in consultation with the grantees after the awards are made.

Table 1

Estimated controls

Data reporting Awardees will collect, store, and transmit data in a standardized and secure manner with common elements mutually agreed upon by CDC and grantees. On a weekly basis, awardees will enter data into the CDC-provided real time web-based study tracking database. Awardees will also be responsible for compiling mailings to be sent to parents (e.g. introductory packets, thank you letters, saliva collection kits, saliva collection thank you letters, various reminders, etc.); these mailings will include incentives as determined by the protocol. Awardees will not conduct the telephone interviews with the participants. Study participants will mail saliva kits to a central study laboratory at the CDC. The final thank you for all participants will notify them that they might be contacted at a later time for additional study components. DNA will be extracted from the saliva samples at the central laboratory and stored in a central biologics repository managed by CDC. Any collected bloodspots will be stored by the grantees at a local facility.

Collaboration Awardees will demonstrate effective relationships and cooperation with appropriate partners (i.e. state officials, cross-department personnel, including informatics personnel within state health department, community based organizations, academic medical center and/or treatment center specializing in these conditions). Ideally, research centers should be a meaningful collaboration between state health departments and academic centers. When appropriate, centers should collaborate and coordinate across state agencies and clinical settings for data collection. Awardees should work with CDC and other grantees to develop and implement standardized processes, methods, data collection, and other project activities. Awardees will provide members for key study committees (e.g., coordinating council, data sharing committee, clinicians committee, and a biologics committee).

Dissemination of information Grantees will be expected to analyze data and publish findings from the BD-STEPS, as well as analyzing data previously collected for the NBDPS. All grantees will be provided access to the NBDPS pooled data upon local IRB approval and for use within the context of data sharing policies. This can include genetic analyses performed at local laboratories and funded through alternative funding sources. The main mode of dissemination of information to the public is through the production and publication of peer-reviewed scientific manuscripts. Each grantee will be expected to publish multiple manuscripts per year. The coordinating council will establish public health priorities each year, and the centers will be expected to prioritize their research accordingly. 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.

Training and mentoring of junior researchers The grantees will be expected to employ junior researchers for training and mentoring such as Masters- and PhD-level students, post-doctoral fellows, medical students and residents, and other junior public health professionals. These junior researchers should gain skills in data analysis, manuscript preparation, and other study related activities through this mentoring to train the future generation of birth defects researchers.

Progress reports The grantees will be expected to provide an annual progress report 90 days after the end of each budget period containing information on the following topics: 1) the timeliness of case identification and transfer to the central database measured from date of birth to date the introduction packet was sent out; 2) the quality of the provided address information measured as rate of initial contact success; 3) the speed with which additional data (case notes, contact information) requests are addressed; 4) the number and title of manuscripts prepared with BD-STEPS or NBDPS data; 5) the number and title of presentations given on BD-STEPS or NBDPS data; and 6) the number of junior researchers that were mentored each year and a description of activities undertaken.

Timeline The anticipated general timeline for the project will consist of 3 phases over 5 years.

Phase 1: Development (Months 1-6)

Phase 2: Data collection and analyses (Months 7-54)

Phase 3: Complete study, ongoing publications and dissemination (Months 55-60)

Objectives/Outcomes The awardees are expected to have produced at least 10 published peer-reviewed manuscripts at the end of the 5 year project period on risk factors for birth defects or other papers furthering the field of birth defects research. The awardees will have trained a number of junior researchers in the field of birth defects and maternal and child health.

Target population The target population is women of childbearing potential, families contemplating pregnancy, public health care professionals, and families of children with and without selected major birth defects.

Collaboration/Partnerships Grantees are expected to establish collaborations between state health departments, educational institutions, other grantees under this FOA, and with the CDC.

Evaluation/Performance measurement The grantees are expected to provide information as listed in the progress report section.

Translation plan 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.

Section II. Award Information

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.

Funds Available and Anticipated Number of Awards

NCBDDD intends to commit approximately $1,750,000 (including both direct and indirect costs) in FY2013 to fund six to nine (6-9) applicants for the first 12 month budget period.

An applicant may request a project period of up to five (5) years. The funding amount is estimated to be $6,000,000 (range from $400,000 to $800,000) (including both direct and indirect costs) each year for the 2nd, 3rd, 4th, and 5th years of the project.

The estimated total funding (direct and indirect costs) for the entire 5 year project period is $25,750,000. An applicant may request a project period of up to 5 years.

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

If an applicant requests a funding amount greater than the ceiling of the award range for the first year ($400,000), HHS/CDC will consider the application non-responsive, and it will not enter into the review process. HHS/CDC will notify the applicant that the application did not meet the submission requirements.

Minimum $125,000 amount (total costs).

The project period is anticipated to be: 8/1/2013 to 7/31/2018.

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://dhhs.gov/asfr/ogapa/aboutog/grantsnet.html) will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information Eligible Applicants

Eligible Organizations

Higher Education Institutions:

· Public/State Controlled Institutions of Higher Education

· Private Institutions of Higher Education

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)

For- Profit Organizations Small Businesses For-Profit Organizations (Other than Small Businesses)

Governments State Governments County Governments City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession

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

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

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

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

3. Special Eligibility Requirements:

Evidence for these criteria must be presented in Appendix A of the application.

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 may include:

· Information on the inclusion of the 17 defects in the birth defects surveillance system that the applicant is planning to use (e.g., web link or data table), and description of access to vital records or birth hospital records.

· Information on the geographical area that covers between 30,000 and 80,000 births annually (e.g. list of counties, table of annual births for recent years).

· If the applicant is not a State health department, inclusion of a letter or memorandum of understanding from the State health department confirming the applicant has access to the necessary data sources in order to ascertain case and control subjects.

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.

System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, http://www.grants.gov/applicants/org_step2.jsp.

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 Central Contractor Registration 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), the replacement system for the Central Contractor Registration (CCR) database. 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://dhhs.gov/asfr/ogapa/aboutog/grantsnet.html).

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

As defined in the HHS Grants Policy Statement, (http://dhhs.gov/asfr/ogapa/aboutog/grantsnet.html), 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.

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/guide/url_redirect.htm?id=12000), 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. These forms can be downloaded and uploaded as Attachment A from the following link: http://www.cdc.gov/od/pgo/funding/grants/foamain.shtm

Letter of Intent Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows 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 to:

Michael A. Brown, M.P.H.

Scientific Program Official Extramural Research Program Office Centers for Disease Control and Prevention 4770 Buford Hwy, NE Mailstop F-46 Atlanta, GA 30341 Telephone: (770) 488-5118

FAX: (770) 488-7863

E-mail: mab5@cdc.gov

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.

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/guide/url_redirect.htm?id=12000) 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_Adobe_VerB.pdf) must be followed along with any additional instructions provided in the FOA.

The research plan should address activities to be conducted over the entire project period and must include the following: