cdc-rfa-ip16-001.pdf

Centers for Disease Control and Prevention

National Center for Immunization and Respiratory Diseases Extramural Research Program Office

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

Viruses in Southeast Asia and the Western Pacific

RFA-IP-16-001

Application Due Date: 01/11/2016

Signature Date

Research on the Epidemiology, Vaccine Effectiveness and Treatment of Influenza and Other Respiratory Viruses in Southeast Asia and the Western Pacific

RFA-IP-16-001

TABLE OF CONTENTS

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

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

Part 1. Overview Information Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations National Center 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, Vaccine Effectiveness and Treatment of Influenza and Other Respiratory Viruses in Southeast Asia and the Western Pacific Activity Code U01 Research Project Cooperative Agreements

Funding Opportunity Announcement Type New Funding Opportunity Announcement Number

RFA-IP-16-001

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

Health FOA Purpose The NCIRD Influenza Division (ID) is seeking a cooperative agreement with the School of Public Health, the University of Hong Kong (UHK), the Peoples’ Republic of China to conduct research studies among older adults on the epidemiology and disease burden of influenza and other respiratory pathogens and to study alternative influenza vaccination strategies, including the relative efficacy of annual or twice-a-year vaccination for influenza. In addition, CDC seeks to collaborate with the UHK to conduct research studies among older adults on novel influenza viruses or other respiratory pathogens, including respiratory syncytial virus (RSV) infection. UHK has an established respiratory virus active surveillance system among older adults in a region of China with twice-yearly periods of influenza circulation which can be utilized to expand and conduct additional research on disease burden and vaccine efficacy in this population. This surveillance platform has allowed the research team at UHK to better understand risk factors for mild to severe influenza disease and its burden; however, it has not generated significant data on influenza vaccine efficacy among older adults. This new cooperative agreement will allow NCIRD ID to expand collaborations with UHK to examine this population in more depth as well as to better understand the best vaccine strategies for this age group and for regions with multiple or year-round epidemic periods. This cooperative agreement would build upon the existing surveillance system in China and the lessons learned from this system could be used in the future to establish a similar project in another country in the Asia-Pacific region.

Key Dates Publication Date: To receive notification of any changes to RFA-IP-16-001, return to the

Publication Date: To receive notification of any changes to RFA-IP-16-001, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link. An email address is needed for this service.

Letter of Intent Due Date: N/A

Application Due Date: 01/11/2016

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: 03/17/2016

Secondary Review: 04/07/2016

Estimated Start Date: 08/01/2016

Expiration Date: 01/12/2016 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 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 NCIRD Influenza Division (ID) is seeking a cooperative agreement with the School of Public Health, the University of Hong Kong (UHK), the Peoples’ Republic of China to conduct research studies among older adults on the epidemiology and disease burden of influenza and other respiratory pathogens and to study alternative influenza vaccination strategies, including the relative efficacy of annual or twice a year vaccination for influenza. In addition, CDC seeks to collaborate with the UHK to conduct research studies among older adults on novel influenza viruses or other respiratory pathogens, including respiratory syncytial virus (RSV) infection. UHK has an established respiratory virus active surveillance system among older adults in a region of China with twice-yearly periods of influenza circulation which can be utilized to expand and conduct additional research on disease burden and vaccine efficacy in this population. This surveillance platform has allowed the research team at UHK to better understand risk factors for mild to severe influenza disease and its burden; however, it has not generated significant data on influenza vaccine efficacy among older adults. This new cooperative agreement will allow NCIRD ID to expand collaborations with UHK to examine this population in more depth as well as to better understand the best vaccine strategies for this age group and for regions with multiple or year-round epidemic periods. This cooperative agreement would build upon the existing surveillance system in China and the lessons learned from this system could be used in the future to establish a similar project in another country in the http://www.grants.gov http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf this system could be used in the future to establish a similar project in another country in the Asia-Pacific region.

Mechanism of Support. Cooperative Agreement Funds Available and Anticipated Number of Awards. Estimated total funding available including direct and indirect costs for the entire project period is $3,000,000 per year. The project period will be 5 years. There will be one award. The total amount awarded will depend upon the availability of funds and receiving a sufficiently meritorious application.

Budget and Project Period. The estimated budget for the first year of this cooperative agreement is $3,000,000. The estimated total funding for the entire project period is up to $15,000,000 for the 5-year project period. The estimated project period for this cooperative agreement is 08/01/2016 to 07/31/2021.

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

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

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and 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. There will only be one PD/PI for this project.

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

Application Type. New Special Date(s). N/A Application Materials. See Section IV.1 for application materials. Please note that Form C is to be used when downloading the application package: http://grants.nih.gov/grants/funding/424/SF424 _RR_Guide_General_VerC.pdf Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY:

(770) 488-2783.

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority Public Health Service Act 307; 42 U.S.C. 242l

1. Background and Purpose Influenza vaccines are the most effective available tools to prevent influenza illness and secondary complications. Randomized controlled trials examining influenza vaccine efficacy and observational studies of influenza vaccine effectiveness (VE) to date indicate that inactivated influenza vaccines (IIV) are moderately effective in preventing influenza illness among all age groups (4); however, there are multiple gaps in our knowledge regarding influenza vaccine efficacy or effectiveness or the best vaccination strategies for older adults.

First, there is limited high quality data on influenza vaccine efficacy or effectiveness for older adults. The only large randomized placebo-controlled efficacy trial conducted among community-dwelling persons aged ≥60 years reported a vaccine efficacy of 58% (95% CI, 26%–77%) against serologically-confirmed symptomatic influenza illness during a season when the vaccine strains were considered to be well-matched to circulating strains (5). However, the validity of using serologic outcomes in vaccine trials has been questioned (4). The results of observational studies on influenza vaccines among older adults are of variable quality and can be difficult to interpret (5-12). A 2010 Cochrane review by Jefferson et al. (13) and the reanalysis of the Cochrane review by Beyer et al. (14) did not reach agreement regarding the effectiveness of influenza vaccines for people aged 65 years or older. Further vaccine efficacy studies among older adults are challenging because random allocation to influenza vaccine or placebo is no longer ethically acceptable in the United States and in many other countries given international recommendations of annual vaccination for all older adults.

Second, there are gaps in our knowledge regarding how underlying health, frailty, and other correlates of aging may impact vaccine efficacy or effectiveness, including through humoral- and cell- mediated immune response to inactivated influenza vaccine (IIV) and the waning of protection over time (15-17).

Third, strategies to improve immunogenicity and VE among older adults are also unclear. Although recent studies indicate that a high antigen dose of IIV may improve VE (18), some studies, especially with non-human animals, suggest providing a booster dose of IIV months after an initial dose may improve immunogenicity for some vaccine strains. In contrast, other studies have observed reduced immunogenicity and VE after repeated annual IIV vaccinations, and the effect of prior vaccination on VE is poorly understood (19).

Fourth, more research is needed to identify the most appropriate influenza vaccination strategy in regions with twice-annual or year-round circulation of influenza. China is located across temperate and subtropical regions with complicated seasonal patterns of influenza transmission. Currently, mainland China follows the vaccination schedule recommended for the Northern Hemisphere countries, with annual campaigns starting in October. However, a recent study identified three epidemiological regions in China that are characterized by distinctly different influenza seasonality. Findings from this study indicate that Northern provinces (latitudes ≥33º N) experience winter epidemics, Southern provinces (latitude <27º N) experience peak activity in the spring and summer, whereas provinces at intermediate latitudes experience twice-annual influenza epidemics (20). This study suggests that region-specific influenza vaccination strategies may be warranted in China.

NCIRD’s Influenza Division has partnered with the UHK School of Public Health in a previous collaboration in 2015 to establish a respiratory infection surveillance cohort of older adults in China. This FOA will build upon the existing capacity to further develop research collaborations in order to address multiple gaps in our knowledge of influenza VE among older adults.

This FOA is to support an evaluation of vaccine immunogenicity and relative efficacy of twice annual vaccination with IIV (administered in the Fall and Spring months) in a location with at least twice-annual influenza epidemics among older adults (defined as individuals aged 60-89 years at the time of enrollment) compared to those who receive a single IIV dose either in the Fall or Spring months. This FOA will support active surveillance of respiratory diseases within an observational cohort of older adults in order to assess the incidence of influenza illness among older adults who are either unvaccinated or receive influenza vaccine according to local standards of medical practice.

Healthy People 2020 and other National Strategic Priorities Healthy People 2020 requirements do not apply to foreign entities.

Public Health Impact The knowledge acquired from the proposed studies under this FOA should allow countries to understand both the burden of influenza illness and influenza vaccine efficacy among older adults, both of which are critical to informing national vaccination policies for this age group. In addition, countries that experience a twice-annual influenza epidemic could utilize this information to determine optimal timing of influenza vaccination, the utility of implementing twice-annual vaccination recommendations, or the relative preventive value of the Northern versus the Southern Hemisphere vaccine regimen in similar regions.

Relevant Work

1. Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States.

JAMA. 2004; 292(11):1333-1340.

2. Feng L, Shay DK, Jiang Y, et al. Influenza-associated mortality in temperate and subtropical Chinese cities, 2003-2008. Bulletin of the World Health Organization. Apr 1 2012; 90(4):279-288B.

3. Dawood FS, Iuliano AD, Reed C, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis. Sep 2012;

12(9):687-695.

4. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. Jan 2012; 12(1):36-44.

5. Govaert TM, Thijs CT, Masurel N, Sprenger MJ, Dinant GJ, Knottnerus JA. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. JAMA. Dec 7 1994;

272(21):1661-1665.

6. Allsup S, Haycox A, Regan M, Gosney M. Is influenza vaccination cost effective for healthy people between ages 65 and 74 years? A randomised controlled trial. Vaccine. Dec 16 2004; 23(5):639-645.

7. Praditsuwan R, Assantachai P, Wasi C, Puthavatana P, Kositanont U. The efficacy and effectiveness of influenza vaccination among Thai elderly persons living in the community. J Med Assoc Thai. Feb 2005;

88(2):256-264.

8. Chen Q, Griffin MR, Nian H, et al. Influenza vaccine prevents medically attended influenza-associated acute respiratory illness in adults aged >/=50 years. The Journal of Infectious Diseases. Apr 1 2015;

211(7):1045-1050.

9. Jackson LA, Jackson ML, Nelson JC, Neuzil KM, Weiss NS. Evidence of bias in estimates of influenza vaccine effectiveness in seniors. International Journal of Epidemiology. Apr 2006; 35(2):337-344.

10.Jackson ML, Nelson JC, Weiss NS, Neuzil KM, Barlow W, Jackson LA. Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study. Lancet. Aug 2 2008; 372(9636):398-405.

11. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med. Oct 4 2007; 357(14):1373-1381.

12. Wong K, Campitelli MA, Stukel TA, Kwong JC. Estimating influenza vaccine effectiveness in community-dwelling elderly patients using the instrumental variable analysis method. Archives of Internal Medicine. Mar 26 2012; 172(6):484-491.

13. Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S, Thomas RE. Vaccines for preventing influenza in the elderly. Cochrane Database Syst Rev. 2010(2):CD004876.

14. Beyer WE, McElhaney J, Smith DJ, Monto AS, Nguyen-Van-Tam JS, Osterhaus AD. Cochrane re-arranged: support for policies to vaccinate elderly people against influenza. Vaccine. Dec 5 2013;

31(50):6030-6033.

15. Goodwin K, Viboud C, Simonsen L. Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine. Feb 20 2006; 24(8):1159-1169.

16. Jackson LA, Nelson JC, Benson P, et al. Functional status is a confounder of the association of influenza vaccine and risk of all cause mortality in seniors. International Journal of Epidemiology. Apr 2006;

35(2):345-352.

17. Yao X, Hamilton RG, Weng NP, et al. Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults. Vaccine.

Jul 12 2011; 29(31):5015-5021.

Jul 12 2011; 29(31):5015-5021.

18. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. Aug 14 2014; 371(7):635-645.

19. McLean HQ, Thompson MG, Sundaram ME, et al. Impact of repeated vaccination on vaccine effectiveness against influenza A(H3N2) and B during 8 seasons. Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America. Nov 15 2014; 59(10):1375-1385.

20. Yu H, Alonso WJ, Feng L, et al. Characterization of regional influenza seasonality patterns in China and implications for vaccination strategies: spatio-temporal modeling of surveillance data. PLoS Med. Nov 2013;

10(11):e1001552.

2. Approach

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

Primary objectives:

- To investigate alternative influenza vaccination strategies for older adults;

- To determine the relative efficacy of twice-annual vaccination versus once-annual vaccination in preventing laboratory-confirmed influenza illness among adults aged 60-89 years in a location with twice-annual epidemics;

- To compare the relative efficacy of providing a single dose of inactivated influenza vaccine (IIV) using the Southern versus the Northern Hemisphere schedule in preventing influenza illness;

- To compare immune response to influenza vaccination among those receiving twice-annual versus annual vaccination;

- To compare the incidence of laboratory-confirmed influenza illness among those who receive IIV (annually or twice-annually) as part of the study versus among older adults in an observational cohort who receive standard local care in a region with little vaccination of older adults.

Secondary objectives:

- To assess the burden of medically-attended and non-medically attended laboratory-confirmed influenza illness among an observational cohort of older adults;

- To estimate the incidence of other respiratory pathogen infections, including respiratory syncytial virus (RSV), associated with acute illness among older adults during periods of local influenza circulation;

- To examine the immune response to repeated influenza vaccinations over multiple years in this older adult age group;

- To compare the immune response to influenza virus illness versus influenza vaccination;

- To evaluate the impact of influenza illness on functional decline in older adults and to evaluate influenza vaccine efficacy in preventing functional decline among older adults;

- To determine whether influenza vaccination reduces the severity of influenza illness among older adults who are infected with influenza despite vaccination;

- To examine the socio-demographic, health, environmental, and immune factors associated with primary or secondary influenza vaccine failure;

- To examine the association between infections with influenza viruses and other pathogens with biomarkers for illness severity;

- To assess risk factors for laboratory-confirmed influenza virus infection among older adults.

Target Population Target populations for research activities include, but are not limited to, older adults (60-89 years of age at the time of enrollment) living in Southeast Asia or the Western Pacific regions.

Collaboration/Partnerships Collaborations with others working in areas of respiratory viruses or vaccine effectiveness in Southeast Asia or the Western Pacific are encouraged. Collaborations with provincial and local public health agencies, as appropriate, are also encouraged. Collaborations with CDC Divisions working in these topic areas are also encouraged.

Evaluation/Performance Measurement As part of the application, the PI must include measurable goals and aims based on a five-year research project period. The applicant 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. The application should develop a timeline to achieve study milestones and develop metrics to monitor the project’s performance and progress. Also, the awardee must submit an annual progress report and an annual budget period progress report for their activities and outcomes based on their overall research goals and timeline. Please see Section VI. Award Administration Information of this FOA for more information on reporting requirements.

Translation Plan The applicant should arrange quarterly meetings with appropriate partners in the areas and countries who will be collaborating under this FOA to discuss research progress and findings. The applicant is requested to identify topics for two manuscripts per year of funding and may include manuscripts for which funding was initiated prior to this cooperative agreement. Likewise, the results of this research should be presented at international conferences and published in peer-reviewed journals.

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: $15,000,000 Estimated total funding available for the first year: $3,000,000

Estimated total funding available for the entire five-year project period: $15,000,000

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: $3,000,000 Per Budget Period Award Floor: $750,000 Per Budget 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 ://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

University of Hong Kong, School of Public Health

Division of Epidemiology and Biostatistics

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 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 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

Additional Information on Eligibility

Eligibility is limited to the Division of Epidemiology and Biostatistics of the School of Public Health, University of Hong Kong (UHK), Hong Kong, Peoples' Republic of China. It is the only advanced research and public health institute with the research and laboratory capacity to conduct an influenza vaccine trial that has also conducted research with a large cohort of older adults in a region with influenza circulation patterns appropriate for the study objectives.

Specifically:

-- The School of Public Health at UHK has established an observational cohort of older adults to monitor the occurrence of illness due to respiratory virus infections in a region of China with multiple periods of influenza circulation each year. This existing cohort can be accessed for the proposed study to aid in addressing CDC's objective to better understand the burden of influenza among older adults.

-- It is in the best interest of CDC to award the cooperative agreement to UHK since the existing recruitment procedures and data systems established for the observational cohort can be applied to the proposed vaccine trial, resulting in substantial cost and time savings for the government.

-- The existing cohort is located in an ideal region for a vaccine trial that intends to compare alternative vaccination schedules and consider the relative protective value of Northern and Southern Hemisphere vaccines.

-- The School of Public Health, UHK, possesses the necessary scientific and managerial capacity for this study and has successfully completed a cooperative agreement with the influenza division related to the 2009 H1N1 influenza pandemic.

-- The research team at the School of Public Health, UHK has experience conducting randomized placebo-controlled trials and other influenza vaccine studies. This expertise is crucial to the success of this cooperative agreement. No other acceptable setting has been identified.

5. Responsiveness N/A

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

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

Grants.gov eRA Commons

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

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

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA 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

Commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

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

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

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

Organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later. SAM is the primary registrant database for the Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient. Additional information about registration procedures may be found at the SAM internet site at https://www.sam.gov/index.html.

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

8. Eligible Individuals (Project Director/Principal Investigator) in Organizations/Institutions Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for HHS/CDC support.

9. Cost Sharing 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 insitutuion (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 – http://fedgov.dnb.com/webform 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

4:30pm U.S. Eastern Standard Time. CDC Telecommunications for the hearing impaired or disabled is available at: TTY 1-888-232-6348.

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

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

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

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, additional data required by the agency for a complete application. While these are not identical to the PHS398 application form pages, the PHS398 reference is used to distinguish these additional data requirements from the data collected in the SF424 (R&R) components. A complete application to CDC will include SF424 (R&R) and PHS398 components.

3. Letter of Intent Due Date for Letter of Intent:

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 mailto:pgotim@cdc.gov

6. Protection of Human Subjects

7. Inclusion of Women and Minorities

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

9. Inclusion of Children

Other Research Plan Sections

10. Vertebrate Animals

11. Select Agent Research

12. Multiple PD/PI Leadership Plan.

13. Consortium/Contractual Arrangements

14. Letters of Support

15. Resource Sharing Plan(s)

16. Appendix

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

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

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

7. Page Limitations All page limitations described in this individual FOA must be followed. For this specific FOA, the Research Strategy component of the Research Plan narrative is limited to 25 pages. Supporting materials for the Research Plan narrative included as appendices may not exceed 10 PDF files with a maximum of 50 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.

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/

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

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

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

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

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

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

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

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

http://grants.nih.gov/grants/guide/url_redirect.htm?id=11128 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11123 mailto:support@grants.gov mailto:www.pgotim@cdc.gov

Due Date for Applications: 01/11/2016

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 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.

Projects that involve the collection of information, identical record keeping or reporting from 10 or more individuals and are funded by a cooperative agreement and constitute a burden of time, effort, and/or resources expended to collect and/or disclose the information will be subject to review and approval by the Office of Management and Budget (OMB) under the Paperwork Reduction Act (PRA).

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 http://www.whitehouse.gov/omb/grants_spoc http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://grants.nih.gov/grants/guide/url_redirect.htm?id=11144 include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to CDC.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

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

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