CDC-RFA-IP16-003.pdf

Centers for Disease Control and Prevention

National Center for Immunization and Respiratory Diseases Extramural Research Program Office

Research on the Epidemiology, Prevention, Vaccine Effectiveness and Treatment of Influenza and Other

Respiratory Viruses in South Africa

RFA-IP-16-003

Application Due Date: 01/15/2016

Research on the Epidemiology, Prevention, Vaccine Effectiveness and Treatment of Influenza and Other Respiratory Viruses in South Africa

RFA-IP-16-003

TABLE OF CONTENTS

Part 1. Overview Information Key Dates Required Application Instructions Executive Summary

Part 2. Full Text Section I. Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 1. Overview Information Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations National Center for Immunization and Respiratory Diseases Extramural Research Program Office (NCIRD

ERPO)

National Center for Immunization and Respiratory Diseases (NCIRD) Funding Opportunity Announcement (FOA) Title Research on the Epidemiology, Prevention, Vaccine Effectiveness and Treatment of Influenza and Other Respiratory Viruses in South Africa Activity Code U01 Research Project Cooperative Agreements

Funding Opportunity Announcement Type New Funding Opportunity Announcement Number

RFA-IP-16-003

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.083 93.283 Category of Funding Activity:

Health FOA Purpose

Key Dates Publication Date: To receive notification of any changes to RFA-IP-16-003, 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.

Letter of Intent Due Date: [Insert 30 days from date of publication] N/A

Application Due Date: 01/15/2016

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

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

Scientific Merit Review: 03/31/2016

Secondary Review: 04/28/2016

Estimated Start Date: 09/01/2016 http://www.grants.gov

Estimated Start Date: 09/01/2016

Expiration Date: 01/16/2016 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 20 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. To conduct research on the epidemiology, disease burden, transmission, risk factors for disease, hospitalization and death, and effectiveness and safety of vaccination and antiviral treatment for influenza and other respiratory diseases of public health importance in South Africa.

Mechanism of Support. Cooperative Agreement.

Funds Available and Anticipated Number of Awards. Estimated total funding available, to include direct and indirect costs for the entire project period, is $14,000,000. The project period will be five

(5) years. There will be one award. The award issued under this FOA is contingent upon availability of funds and the total number of meritorious applications received.

Budget and Project Period. The estimated total funding (direct and indirect) for the first (12-month) budget period will be $3,000,000. The project period will run from 09/01/2016 to 08/31/2021.

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. Eligibility is limited to the National Institute for Communicable Diseases, Johannesburg, South Africa.

Number of PDs/PIs. There will only be one PD/PI for this project.

Number of Applications. Each eligible applicant institution may submit only one application.

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

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

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority Public Health Service Act, Section 307 [42 U.S.C. 242l]

1. Background and Purpose The NCIRD Influenza Division (ID) is seeking to initiate a cooperative agreement to conduct research on the http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf

The NCIRD Influenza Division (ID) is seeking to initiate a cooperative agreement to conduct research on the epidemiology, disease burden, transmission, risk factors for disease, hospitalization, and death, and effectiveness and safety of vaccination and antiviral treatment for influenza and other respiratory pathogens of public health importance. Only the National Institute for Communicable Diseases (NICD), Republic of South Africa is eligible to apply to this FOA.

As a middle income country with high HIV prevalence, South Africa is uniquely positioned in Africa to conduct implementation research on influenza vaccination. The government of South Africa through the Department of Health (DOH) procures approximately 1 million doses of influenza vaccine annually for distribution in the public sector. Recommended target groups for influenza vaccination in South Africa include pregnant women, young children, the elderly, healthcare workers and persons with chronic diseases, including HIV. Furthermore, the only influenza vaccine manufacturing capacity in Africa will be in South Africa and will produce inactivated influenza vaccine for the 2016 Southern Hemisphere season. Despite these advantages, influenza vaccine coverage among target groups remains less than 10% annually.

Over the last 9 years, the CDC’s Influenza Division has collaborated with the NICD to conduct influenza surveillance to better understand influenza seasonality, determine risk factors for severe disease, and to estimate morbidity and mortality attributable to influenza virus infections. However, the existing surveillance platforms are insufficiently powered to examine risk groups or rare outcomes, which has left critical gaps in our knowledge and understanding of influenza epidemiology. Addressing these gaps will inform future policy decisions by WHO’s Strategic Advisory Group of Experts (SAGE) and the South African Department of Health on influenza immunization. Assessments of household and community transmission of influenza viruses has only just begun. Likewise, we have limited understanding of the safety and effectiveness of influenza vaccination and antiviral treatment in special populations (e.g., pregnant women, HIV-infected children and adults) or the utility of non-pharmaceutical interventions (e.g., hand washing and respiratory hygiene campaigns). Research conducted as part of this cooperative agreement will seek to fill these gaps in the understanding of influenza epidemiology in South Africa and other African countries.

Healthy People 2020 and other National Strategic Priorities This award addresses the “Healthy People 2020” focus area(s) of Immunization and Infectious Diseases and is in alignment with NCIRD’s performance goal(s) to protect Americans from infectious diseases and “Protecting the Nation’s Health in an Era of Globalization: CDC’s Global Infectious Disease Strategy”.

Public Health Impact Identification of risk groups for severe influenza infection is key to appropriately targeting interventions including vaccines and antivirals in resource-limited settings. Likewise, assessing the safety and effectiveness of influenza vaccines in these populations is important to ensure acceptability, improve influenza vaccine coverage and to impact disease burden.

Relevant Work Cohen C, Moyes J, Tempia S, Groome M, Walaza S, Pretorius M, et al. Mortality amongst patients with influenza-associated severe acute respiratory illness, South Africa, 2009-2013. PLOS ONE 2015;

10(3): 1-15.

Tempia S, Walaza S, Viboud C, Cohen A, Madhi S A, Venter M, von Mollendorf C, Moyes J, McAnerney J, Cohen C. Deaths associated with respiratory syncytial and influenza viruses among persons ≥5 years of age in HIV-prevalent area, South Africa, 1998–2009. Emerging Infectious Diseases 2015; 21(4): 600-608 Tempia S, Walaza S, Viboud C, Cohen A, Madhi S A, Venter M, McAnerney J, Cohen C. Mortality associated with seasonal and pandemic influenza and respiratory syncytial virus among children <5 years of age in a high HIV prevalence setting—South Africa, 1998–2009. Clinical Infectious Diseases 2014; 58(9):1241–9 Walaza S, Tempia S, Dawood H, Variava E, Moyes J, Cohen A, Wolter, N, et al. Influenza virus

Walaza S, Tempia S, Dawood H, Variava E, Moyes J, Cohen A, Wolter, N, et al. Influenza virus infection is associated with increased risk of death amongst patients hospitalized with confirmed pulmonary tuberculosis in South Africa, 2010–2011. BMC Infectious Diseases (2015) 15:26: 1-13 Cohen C, Moyes J, Tempia S, Groome M, Walaza S, Pretorius M, et al. Severe influenza-associated respiratory infection in high HIV prevalence setting, South Africa, 2009–2011. Emerging Infectious Diseases 2013; 19(11): 1766-1774

2. Approach

Objectives/Outcomes Whenever possible, applications should include objectives written in the SMART format (e.g., Specific, Measurable, Achievable, Realistic and Time-bound).

All of the primary objectives listed below must be addressed in the application’s research plan.

Primary Objectives:

1. Assess the safety, effectiveness, and impact of influenza vaccines in preventing laboratory-confirmed influenza, through observational studies of existing public-sector programs, phase IV demonstration projects or intervention studies. If possible, evaluate the differential effectiveness or efficacy among subpopulations where effectiveness/efficacy might be reduced (e.g., pregnant women, HIV-infected children and adults, young children, etc.).

2. Estimate the prevalence and clinical spectrum, pathogenesis and outcomes of severe pneumonia and/or severe acute respiratory infection (SARI) caused by influenza viruses and other respiratory pathogens and differences of these parameters among population sub-groups at possibly increased risk for disease (e.g., by racial/ethnic groups, age groups, economic status, and presence of high risk conditions such as pregnancy, malnutrition, HIV-infection, etc.).

3. Establish and/or maintain partnerships with regional/sub-regional ministries of health and agriculture, provincial and municipal health departments, academic institutions, vaccine manufacturers, or others to facilitate access and cooperation in meeting research study objectives.

In addition to the primary objectives, the following additional objectives may also be addressed:

Assess the safety of influenza vaccines in subpopulations through monitoring of adverse events following immunization, or special studies assessing impact of influenza vaccine on pregnancy/birth outcomes, growth in infancy, etc.

Evaluate the impact of influenza-associated hospitalization on young infant development and growth through a case-control or case-cohort study design.

Evaluate community and intra-household transmission dynamics of influenza and other respiratory viruses including secondary attack rates, effective reproductive number, and duration of viral shedding among sub-populations of different age, race, HIV serostatus, etc.

Assess patterns of healthcare utilization in communities with ongoing influenza surveillance to inform burden of disease estimates.

Evaluate hospital-associated respiratory infections through implementation of surveillance for influenza and other respiratory viruses among persons hospitalized >2 days with new onset respiratory symptoms.

Estimate the direct and indirect economic burden of influenza disease among a range of different subpopulations, including assessment of cost-effectiveness of influenza vaccination for priority groups.

Estimate the potential impact of vaccine introduction in different target groups on influenza-associated disease burden.

Evaluate the immunogenicity, safety, effectiveness and duration of protection of newer influenza vaccines (e.g., live attenuated influenza vaccines, intradermal influenza vaccines, high dose influenza vaccines, adjuvanted influenza vaccines, etc.) in priority risk groups.

Perform, or arrange to have performed, laboratory influenza assays including: serology for influenza antibodies by CDC approved methods, typing and subtyping of strains, antigenic characterization, sequencing and isolation of viruses as appropriate, and other laboratory assays such nutritional markers.

Participate in scientific trainings, meetings, scientific collaborations and WHO- or CDC-sponsored proficiency testing.

Increase influenza epidemiologic and laboratory surveillance capacity in the WHO African Region by providing training, technical assistance, and laboratory support to other African nations.

Regularly disseminate and report surveillance and research findings including: 1) participating fully in the Global Influenza Surveillance and Response System (GISRS) by routinely, and in a timely manner, submitting quality, current specimens to WHO Collaborating Centers and data through WHO electronic systems; 2) making regular data available to partners within the country through surveillance reports or website summaries; and 3) publishing results of research studies in peer-reviewed scientific journals in a timely manner (i.e., within 12 months of study completion).

Maintain a system and protocol to rapidly notify national government authorities and WHO of suspect human cases infected with a novel influenza A virus including H5 and H7 or other zoonotic viruses in humans. The protocol should include providing appropriate samples for testing at the national level and sending samples to a WHO Collaborating Center for testing and confirmation. A protocol for sending unsubtypable virus samples to a WHO Collaborating Center should also be in place.

Target Population All temporary or permanent residents of South Africa and the region regardless of citizenship, race, or gender.

Collaboration/Partnerships Applicants are expected to establish and/or maintain partnerships with regional/sub-regional ministries of health and agriculture, provincial and municipal health departments, academic institutions, or others to facilitate access and cooperation in meeting research study objectives.

Evaluation/Performance Measurement The applicant will be evaluated on their ability to conduct policy-relevant research to identify groups at risk for influenza-associated morbidity/mortality, describe influenza transmission dynamics in households and/or communities, and describe differences in vaccine effectiveness among targeted risk groups. They will also be evaluated on the timely dissemination of these results to in-country partners and the larger research community through peer-reviewed publications. Primary publications should be submitted for CDC clearance within 12 months of completion of field work (data and specimen collection).

As part of the application, the PI should include measurable goals and aims based on the five-year research project period. The grantee will collaborate with CDC to: (1) establish specific, measurable, achievable, realistic and time-phased (SMART) project objectives for each activity described in the applicant’s project plan, and (2) develop and implement project performance measures that are based on specific programmatic objectives. Also, funded PIs must submit an annual progress report showing their activities and outcomes based on their overall research goals and timeline. For more information on required Reporting, please see Section VI of this FOA.

Translation Plan Applicants must include a plan to estimate and report the potential translatability and public health impact of the research. Findings should be disseminated to local stakeholders, including the local Department of Health, to inform vaccine policy review.

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: $14,000,000 Year 1: $3,000,000

Year 2: $3,000,000

Year 3: $3,000,000

Year 4: $3,000,000

Year 5: $2,000,000

Anticipated Number of Awards: 1

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

Award Ceiling: $5,000,000 Per Project Period Award Floor: $1,000,000 Per Project Period Total Project Period Length: 5 year(s)

Throughout the project period, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

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

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category: Others (see text field entitled "Additional Information on Eligibility" for clarification)

2. Foreign Organizations Foreign Organizations are eligible to apply.

Foreign (non-US) organizations must follow policies described in the HHS Grants Policy Statement (http http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf

Foreign (non-US) organizations must follow policies described in the HHS Grants Policy Statement (http ://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf), and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. International registrants can confirm DUNS by sending an e-mail to ccrhelp@dnb.com, including Company Name, D-U-N-S Number, and Physical Address, and Country. Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https ://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf .

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 Additional Information on Eligibility

Single-Source Competition

National Institute for Communicable Diseases, Republic of South Africa

Applications submitted under this funding opportunity announcement must not include activities that overlap with simultaneously-funded research under other awards.

4. Justification for Less than Maximum Competition Eligibility is limited to the National Institute for Communicable Diseases (NICD), Johannesburg, South Africa, because: 1) it is the only sufficiently advanced research and public health institute and laboratory in the sub-region that can perform the types of sophisticated studies and laboratory analyses required to understand influenza disease burden, vaccine effectiveness, and treatment outcomes that is also located in an area of high HIV prevalence in the Southern Hemisphere; 2) over $8,000,000 has been spent during the last two cooperative agreements with NICD to build influenza surveillance infrastructure in five provinces of South Africa. Other applicants would need to build this infrastructure from the very beginning, costing millions of dollars and precious time that could be spent on conducting the studies proposed in this FOA. It is therefore in the government's best interest to award funds to NICD to complete the proposed studies.

Failure to award funds to NICD to continue and expand upon influenza surveillance in the region would negatively impact our understanding of influenza transmission dynamics in South Africa and the region and our understanding of vaccine effectiveness in high-risk groups (e.g., pregnant women, young infants, and persons with HIV).

Other points to consider:

NICD is the National Public Health Institute for South Africa. It provides reference microbiology, virology, epidemiology, surveillance and public health research to support the government's response to communicable disease threats.

NICD serves as the National Influenza Center for South Africa and provides technical assistance on influenza surveillance and diagnosis to other countries in the sub-region. NICD staff have provided technical assistance to the Democratic Republic of Congo, Malawi, Mozambique, Zambia, etc.

NICD has cooperated with NCIRD's Influenza Division, Division of Bacterial Diseases and Division of Viral Diseases to conduct respiratory disease surveillance, post-introduction assessments of vaccine impact; influenza household transmission studies; influenza, rotavirus and pneumococcal disease burden estimates; vaccine effectiveness studies and disease modeling studies.

Currently, NICD is a division of the National Health Laboratory Service (NHLS). The NHLS has also hosted successful collaborations with the CDC Center for Global Health's Division of Global Health Protection and Division of Tuberculosis Elimination.

http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf mailto:ccrhelp@dnb.com 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

NICD possesses the scientific and management capability to meet program requirements without jeopardizing or compromising the quality of the research and other activities.

NICD has managed Influenza Division non-research cooperative agreement funds well for the past 9 years. This partnership has built a hospital-based severe acute respiratory illness (SARI) platform that has been used to provide national disease burden estimates, examine HIV and TB as risk factors for severe influenza disease, and improve understanding of household transmission in South Africa.

5. Responsiveness Only applications submitted by the National Institute for Communicable Diseases (NICD), Johannesburg, South Africa will be considered responsive to this application. Applications submitted by other organizations will be considered nonresponsive and these applications will not move forward to peer review or be eligible for funding.

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

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

Grants.gov eRA Commons

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

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

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

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

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

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

Organizations must maintain the registration with current information at all times during which it has an 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 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.

Section IV. Application and Submission Information

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

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

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/ 424/SF424_RR_Guide_General_VerC.pdf), except where instructed in this Funding Opportunity Announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, https://www.sam.gov/index.html http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.Grants.gov mailto:pgotim@cdc.gov 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: [Insert 30 days from date of publication] N/A

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.

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 20 pages. Supporting materials for the Research Plan narrative included as appendices may not exceed 10 PDF files with a maximum of 25 pages for all appendices.

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

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

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

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

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

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

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

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

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/funding/424/SF424_RR_Guide_General_VerC.pdf http://grants.nih.gov/grants/guide/url_redirect.htm?id=11128 http://www.grants.gov/ http://grants.nih.gov/grants/guide/url_redirect.htm?id=11123

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; 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: 01/15/2016

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).

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.

Funds related to the conduct of research involving human subjects will be restricted until the appropriate mailto:support@grants.gov mailto:www.pgotim@cdc.gov http://www.whitehouse.gov/omb/grants_spoc

Funds related to the conduct of research involving human subjects will be restricted until the appropriate assurances and Institutional Review Board (IRB) approvals are in place. Copies of all current local IRB approval letters and local IRB approved protocols (and CDC IRB approval letters, if applicable) will be required to lift restrictions.

The Paperwork Reduction Act of 1995 (PRA): Applicants should be advised that any activities involving information collection (i.e., posing similar questions or requirements via surveys, questionnaires, telephonic requests, focus groups, etc.) from 10 or more non-Federal entities/persons, including States, are subject to PRA requirements and may require CDC to coordinate an Office of Management and Budget (OMB) Information Collection Request clearance prior to the start of information collection activities. This would also include information sent to or obtained by CDC via forms, applications, reports, information systems, and any other means for requesting information from 10 or more persons; asking or requiring 10 or more entities/persons to keep or retain records; or asking or requiring 10 or more entities/persons to disclose information to a third-party or the general public.

On September 24, 2014, the Federal government issued a policy for the oversight of life sciences “Dual Use Research of Concern” (DURC) and required this policy to be implemented by September 24, 2015. This policy applies to all New and Renewal awards issued on applications submitted on or after September 24, 2015, and to all non-competing continuation awards issued on or after that date. CDC grantee institutions and their investigators conducting life sciences research subject to the Policy have a number of responsibilities that they must fulfill. Institutions should reference the policy, available at http://www.phe .gov/s3/dualuse, for a comprehensive listing of those requirements.

Non-compliance with this Policy may result in suspension, limitation, or termination of United States Government (USG) funding, or loss of future USG funding opportunities for the non-compliant USG-funded research project and of USG funds for other life sciences research at the institution, consistent with existing regulations and policies governing USG funded research, and may subject the institution to other potential penalties under applicable laws and regulations.

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) http://www.phe.gov/s3/dualuse http://www.phe.gov/s3/dualuse http://grants.nih.gov/grants/guide/url_redirect.htm?id=11144

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 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?

Does the project advance understanding of risk groups for influenza-associated morbidity/mortality?

Does the project advance understanding of influenza vaccine effectiveness in populations targeted for vaccination?

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

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?

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?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining…