oppRFA-IP-18-004-cfda93.083-cidRFA-IP-18-004-instructions.pdf

Centers for Disease Control

National Center for Immunization and Respiratory Diseases Extramural Research Program

Office

Public Health Epidemiology of Influenza Virus Infection and Control in China

RFA-IP-18-004

Application Due Date: 03/21/2018

Public Health Epidemiology of Influenza Virus Infection and Control in China

RFA-IP-18-004

TABLE OF CONTENTS

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

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

Part 1. Overview Information Participating Organization(s) Centers for Disease Control Components of Participating Organizations National Center for Immunization and Respiratory Diseases Extramural Research Program Office (NCIRD ERPO) Notice of Funding Opportunity (NOFO) Title Public Health Epidemiology of Influenza Virus Infection and Control in China Activity Code U01 - Research Project - Cooperative Agreements

Notice of Funding Opportunity Type New Agency Notice of Funding Opportunity Number

RFA-IP-18-004

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

Health NOFO Purpose The purpose of this Notice of Funding Opportunity (NOFO) is to partner with the Chinese Center for Disease Control and Prevention (China CDC) to support enhanced influenza surveillance and applied research to better define the global risk of novel and seasonal influenza virus infections in humans and animals in China, the region and the world. The scope of research performed will include, but will not be limited to, activities that: a) determine the impact of influenza among vulnerable populations; b) assess the value of antiviral medications, vaccines and other mitigation strategies, and c) support and guide seasonal epidemic and pandemic influenza prevention and control studies. Research activities for the prevention and control of novel influenza viruses and pandemic preparedness activities will be aimed at preventing and controlling the spread and transmission of novel influenza viruses to other countries, including the United States. Continued monitoring, detection, and reporting of these novel influenza viruses in China will advance efforts to inform global health infection control policies and prevent and control seasonal epidemic and pandemic influenza in countries around the world.

Key Dates Publication Date: To receive notification of any changes to RFA-IP-18-004, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link. An email address is https://www.grants.gov needed for this service.

Letter of Intent Due Date: 01/23/2018

Application Due Date: 03/21/2018

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: 05/15/2018

Secondary Review: 06/07/2018

Estimated Start Date: 09/30/2018

Expiration Date: 03/22/2018 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 NOFO. Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Note: The Research Strategy component of the Research Plan is limited to 25 pages.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Executive Summary

Purpose: The purpose of this Notice of Funding Opportunity (NOFO) is to partner with the Chinese Center for Disease Control and Prevention (China CDC) to support enhanced influenza surveillance and applied research to better define the global risk of novel and seasonal influenza virus infections in humans and animals in China, the region and the world. The scope of research performed will include, but will not be limited to, activities that: a) determine the impact of influenza among vulnerable populations; b) assess the value of antiviral medications, vaccines and other mitigation strategies, and c) support and guide seasonal epidemic and pandemic influenza prevention and control http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf studies. Research activities for the prevention and control of novel influenza viruses and pandemic preparedness activities will be aimed at preventing and controlling the spread and transmission of novel influenza viruses to other countries, including the United States. Continued monitoring, detection, and reporting of these novel influenza viruses in China will advance efforts to inform global health infection control policies and prevent and control seasonal epidemic and pandemic influenza in countries around the world.

Mechanism of Support: U01 - Research Project - Cooperative Agreement Funds Available and Anticipated Number of Awards: The estimated total funding available, including direct and indirect costs, for the entire five (5)-year project period is $10,000,000. The anticipated number of awards will be one. Awards issued under this NOFO are contingent upon availability of funds and a sufficiently meritorious application. Because the nature and scope of the proposed research will vary from application to application, it is also anticipated that the size and duration of each award may also vary. The total amount awarded and the number of awards will depend upon the number, quality, duration and cost of the applications received.

Budget and Project Period: The estimated total funding (direct and indirect) for the first year (12-month budget period) will be a maximum of $2,000,000 with an individual award ranging from $1,000,000 to $2,000,000 for the first year. The estimated total funding (direct and indirect) for the entire project period will be a maximum of $10,000,000. The project period is anticipated to run from 9/30/2018 to 9/29/2023.

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

Eligible Institutions/Organizations. Institutions/organizations listed in Section III.1 of this announcement 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 each application.

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

Application Type. New.

Application Materials. See Section IV. 1 for application materials. Please note that

Form E is to be used when downloading the application package.

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority Public Health Service Act, Sections 301(a) [42 U.S.C. 241(a)] and 307 [42 U.S.C. 242l]

1. Background and Purpose The National Center for Immunization and Respiratory Diseases (NCIRD), Influenza Division (ID), seeks to initiate a cooperative agreement with the Chinese Center for Disease Control and Prevention (China CDC), Beijing, China. The purpose of this collaboration is to support enhanced influenza surveillance and applied research to better define the global risk of novel and seasonal influenza virus infections in humans and animals in China, the region and the world. The scope of research performed will include, but will not be limited to, activities that: a) determine the impact of influenza among vulnerable populations; b) assess the value of antiviral medications, vaccines and other mitigation strategies, and c) support and guide seasonal epidemic and pandemic influenza prevention and control studies. Research activities for the prevention and control of novel influenza viruses and pandemic preparedness activities will be aimed at preventing and controlling the spread and transmission of novel influenza viruses to other countries, including the United States. Continued monitoring, detection, and reporting of these novel influenza viruses in China will advance efforts to inform global health infection control policies and prevent and control seasonal epidemic and pandemic influenza in countries around the world.

In 1997, the highly pathogenic avian influenza A (H5N1) virus emerged in China and resulted in several outbreaks in poultry and infections in humans that affected other countries in Southeast Asia. The last human infections with A (H5N1) virus in China were in 2016. Since 2003, there have been 53 human infections with A (H5N1) virus in China and, of those, 31 (59%) have died.

In 1998, the National Health and Family Planning Commission in China also reported human infections with avian influenza A (H9N2) virus. Whereas the A (H9N2) influenza virus tends to cause milder illness in humans than the A (H5N1) virus, it continues to circulate. To date, there have been 34 human infections reported from China out of a total 41 reported worldwide.

In 2013, the first human infections with avian influenza A (H7N9) virus were reported from China. Through five annual epidemic periods, approximately 1,561 human infections were reported. Of those, approximately 90% resulted in severe illness and 40% died. Of the 1,561 infections, some sporadic detection with associated travel to China has been detected in other countries. Whereas human-to-human transmission is rare, and there has been no evidence of sustained transmission between humans, vigilance in the detection and testing of these viruses is critical to monitor changes in the virus that could make populations within and outside of China at risk for infection. Since the emergence of A (H7N9) virus, human infections of avian influenza A (H5N6), A (H10N8) and A (H6N1) viruses have also been detected and reported in China.

Supporting China CDC in their efforts to monitor, detect, control, and prevent infections in humans is critical to preventing the worldwide spread of A (H7N9) and other novel influenza viruses currently circulating in China. The continued detection of novel viruses in China, coupled with the possibility of genetic mutations, or re-assortment with constantly circulating human influenza A viruses, underscores the importance of continuous monitoring and the development of an evidence-base for best practices related to novel influenza virus detection, preparedness, response, and mitigation within the country.

In Asia, China is uniquely positioned to conduct implementation research to assess risks associated from seasonal and novel influenza viruses and to evaluate the benefit and effectiveness of influenza vaccination and other prevention strategies in vulnerable populations. China CDC houses a WHO-designated National Influenza Center and also serves as a WHO Collaborating Center for Influenza. The China CDC National Influenza Center regularly performs WHO and CDC proficiency panels, shares viruses with international WHO Collaborating Centers for Influenza and the Global Influenza Surveillance and Response System, and has the capacity to rapidly identify novel viruses such as, but not limited to, influenza A (H5N1) and A (H7N9) viruses. China CDC has also published guidelines on seasonal influenza vaccination among high risk groups. Recommended target groups for influenza vaccination in China follow the WHO Strategic Advisory Group of Experts (SAGE) recommendations for influenza vaccine and include: pregnant women, young children, the elderly, healthcare workers and persons with chronic diseases. Despite an existing influenza vaccination policy, influenza vaccination coverage remains at less than 2% for most target groups. This demonstrates the need for additional data to support increased vaccine supply and uptake.

Seasonal influenza vaccine coverage is higher in some municipalities and regions of China that have local policies for vaccinating certain at-risk populations. In Beijing, for example, annual seasonal influenza vaccination is offered free of charge to adults aged 60 years and older and to school children. Coverage in these high risk groups approaches 50% in Beijing. Having a system in place for seasonal vaccination will facilitate use of a pandemic vaccine, if and when it is needed. China is also one of the few middle-income countries with several local vaccine manufacturers who are currently developing pandemic influenza vaccines. In 2015, one of China’s local biological manufacturers became the first to produce a WHO pre-qualified seasonal influenza vaccine. This allowed the donation of influenza vaccine from China to several resource-poor countries.

CDC’s Influenza Division has collaborated with China CDC for more than 20 years. Activities include conducting influenza surveillance to better understand influenza seasonality, determining risk factors for severe disease, evaluating risk factors for transmission of novel influenza viruses at the animal-human interface, and estimating morbidity and mortality attributable to influenza virus infections. However, information on risk of influenza, and effectiveness of influenza vaccination and other prevention measures in vulnerable populations (e.g., pregnant women, persons with underlying medical conditions, the elderly, infants, and healthcare workers), is still limited. In addition, few data are available on the epidemiology and risk of infection with avian influenza A (H7N9) virus and the effectiveness of mitigation strategies. Addressing these gaps will inform global assessment of the risk posed by novel influenza viruses with pandemic potential and decisions about the need for influenza vaccine development, procurement, and stockpiling for target groups. Enhanced surveillance, program evaluation and research, conducted as part of this cooperative agreement, will seek to fill these gaps in our understanding of seasonal and novel influenza epidemiology in Asia.

Healthy People 2020 and other National Strategic Priorities Not applicable.

Public Health Impact Defining the risk of novel and seasonal influenza virus infections in humans and animals through influenza surveillance, vaccine program evaluations, and special studies among vulnerable populations is critical to maintaining preparedness to detect and respond to seasonal influenza epidemics and pandemics. Likewise, assessing the safety and value of influenza and other respiratory pathogen vaccines, antiviral medications, and other mitigation strategies in vulnerable populations is important to ensure acceptability and feasibility of influenza and other respiratory pathogen prevention strategies and to optimize strategies to reduce the burden of associated illness. Finally, identifying optimal strategies for vaccine delivery and improved risk communications will improve the implementation of existing influenza policies and guidelines.

To date, China is the only country with ongoing circulation of avian influenza A (H7N9) virus in poultry, the environment, and humans. In addition to this virus, other avian influenza viruses have been detected in humans in China in the last five years including A (H6N1), A (H9N2), A (H5N1), and A (H10N8) viruses. There is ongoing concern that the next pandemic of influenza could emerge in China, posing a world-wide risk of infection in people. Defining the risk of novel and seasonal influenza virus infections in humans and animals by strengthening surveillance for influenza viruses and conducting program evaluations and special studies among vulnerable populations, is critical to maintaining preparedness to detect and respond to influenza pandemics and seasonal influenza epidemics. Likewise, assessing the safety and effectiveness of influenza vaccines, antiviral medications, and other mitigation strategies in vulnerable populations is important to: 1) ensure acceptability and feasibility of influenza prevention strategies and 2) develop strategies to reduce the burden of influenza-associated illness. Information obtained through collaborations with China expedite information sharing and are critical to trigger the rapid development of candidate vaccine viruses at CDC. These candidate vaccine viruses can be used for vaccine production, clinical trials, stockpiling and other pandemic preparedness purposes based on ongoing public health risk assessment.

Relevant Work

1. World Health Organization Influenza Surveillance and Monitoring. http://www.who.int /influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en/

2. World Health Organization, Human infection with avian influenza A (H7N9) virus – China. http://www.who.int/csr/don/07-august-2017-ah7n9-china/en/

3. CDC National Center for Immunization and Respiratory Diseases, Influenza Division International Program. https://www.cdc.gov/flu/international/program/index.htm

4. CDC, Asian Lineage Avian Influenza A (H7N9) Virus https://www.cdc.gov/flu/avianflu /h7n9-virus.htm

5. RFA-GH-17-005: Conducting Public Health Research in China. https://www.grants.gov /web/grants/view-opportunity.html?oppId=292309

6. RFA-IP-16-1605: Maintenance of Influenza Surveillance Capacity by National Health Authorities Outside the United States. https://www.grants.gov/web/grants/view-opportunit y.html?oppId=283956

The activities described in this NOFO build upon more than 20 years of laboratory and surveillance capacity building. CDC currently provides funding to China through several Cooperative Agreements, including RFA-GH-17-005 and RFA-IP-16-1605, to support seasonal influenza surveillance activities. The activities stipulated in this NOFO build upon this laboratory and research capacity by supporting new activities to: 1) enhance novel influenza virus surveillance and evaluation interventions that might be used during outbreak responses, and 2) test mitigation and control strategies to be employed during pandemics.

http://www.who.int/influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en/ http://www.who.int/influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en/ http://www.who.int/csr/don/07-august-2017-ah7n9-china/en/ https://www.cdc.gov/flu/international/program/index.htm https://www.cdc.gov/flu/avianflu/h7n9-virus.htm https://www.cdc.gov/flu/avianflu/h7n9-virus.htm https://www.grants.gov/web/grants/view-opportunity.html?oppId=292309 https://www.grants.gov/web/grants/view-opportunity.html?oppId=292309 https://www.grants.gov/web/grants/view-opportunity.html?oppId=283956 https://www.grants.gov/web/grants/view-opportunity.html?oppId=283956

2. Approach To accomplish the goals of this NOFO, the applicant organization should submit a research application that addresses one or more of the public health issues and priorities identified under the Objectives/Outcomes outlined below.

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

Objectives/Outcomes

Assess and enhance surveillance and laboratory capacity to rapidly and reliably identify and respond to novel influenza viruses with pandemic potential.

Determine the disease and economic burden of influenza illness among vulnerable populations in China including, but not limited to, older adults, individuals with chronic health conditions, pregnant women, children less than 5 years of age, healthcare workers, and workers in the poultry industry.

Evaluate possible improvements to the prevention and control of novel avian influenza viruses in commercial poultry settings.

Assess the potential value of increasing influenza vaccination coverage among vulnerable populations in China. These might include evaluations and studies of “second generation” influenza vaccines (e.g., live attenuated influenza, intradermal influenza, high dose, adjuvanted, and cell-based influenza vaccines) that have the potential to offer broader, or longer lasting, immunity and/or improved immune response.

Assess the value of novel influenza vaccination and other influenza prevention, treatment, and mitigation strategies (e.g., antiviral medications, non-pharmaceutical interventions) through program evaluations. Assessments might also include observational studies of existing public-sector programs, phase IV demonstration projects, or intervention studies among subpopulations at high risk of complications for influenza illness and where effectiveness/efficacy might be reduced (e.g., older adults).

Assess communication and community outreach strategies to improve influenza vaccine acceptability and uptake, particularly in vulnerable populations.

Define the risk of novel and seasonal influenza virus infections in humans and animals, especially among populations with increased exposure to novel viruses or vulnerable populations.

Assess the safety of influenza vaccines in subpopulations by monitoring adverse events following immunization, or conduct special studies assessing the impact of influenza vaccine or antiviral treatment.

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.

Research performed under this NOFO will include regular dissemination and reporting of surveillance and research findings through: 1) continued participation in the Global Influenza Surveillance and Response System (GISRS) by routinely sharing quality specimens with other

WHO Collaborating Centers and by sharing 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).

Target Population The target population includes all migrant or permanent residents of China, with a focus on populations identified by WHO as being at increased risk for severe influenza and/or a target group for influenza vaccination. This includes, but is not limited to: pregnant women, healthcare workers, poultry workers and other persons with occupational risk for influenza infection, children 6 to 59 months of age, older adults, and those with high risk medical conditions. Results from these activities will also indirectly inform and benefit the US and other world populations.

Collaboration/Partnerships Activities supported by this NOFO will build upon existing partnerships with local and provincial centers for disease control and ministries of agriculture or other organizations important for pandemic preparedness within China. New and established 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, will also be supported.

Evaluation/Performance Measurement As part of the application, the PI should include measurable goals and aims based on a five (5)-year research project period. The initial application should describe goals for all five years, with an emphasis on the activities for the first year. If awarded, subsequent continuation applications should describe progress towards the long-term goals from the previous year, and emphasize research activities for each subsequent year. The grantee will establish specific, measurable, achievable, realistic and time-phased (SMART) project objectives for each activity described in the application’s project plan, and develop and implement project performance measures that are based on specific programmatic objectives.

Translation Plan Applications should include a plan to estimate and report upon the potential translatability and public health impact of the proposed research. Findings should be disseminated to local, regional, and international stakeholders including, but not limited to: the National Health and Family Planning Commission, China; the Ministry of Agriculture in China; and relevant provincial and local health bureaus and centers for disease control. Dissemination of this information will inform and foster review of influenza vaccination and other prevention policies, as well as pandemic preparedness activities. Information on seasonal and novel influenza virus detection should be shared globally with WHO and other partners through the use of a surveillance report or other publication.

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: $10,000,000

Year 1: $2,000,000 Year 2: $2,000,000 Year 3: $2,000,000 Year 4: $2,000,000 Year 5: $2,000,000

Estimated total funding available for the first year (12-month budget period), including direct and indirect costs: $2,000,000 Estimated total funding available for the entire five (5)-year project period, including direct and indirect costs: $10,000,000

Anticipated Number of Awards: 1 Awards issued under this NOFO are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

The ceiling and floor amounts listed below are for individual awards for the first 12-month budget period.

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

Award Ceiling: $2,000,000 Per Budget Period Award Floor: $0 Per Budget Period Total Period of Performance Length: 5 year(s)

Throughout the Period of Performance, 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

(https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this NOFO.

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category: Others (see text field entitled "Additional

Information on Eligibility" for clarification)

Additional Eligibility Category:

Other:

Foreign Organizations: a Foreign

Organization is a public or private organization, whether non-profit or for-profit, located in a country other than the United States (U.S.) and its territories that is subject to the laws of the country in which it is located, irrespective of the citizenship of project staff or place of performance.

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/AC135 Public/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 Eligibility of this cooperative agreement is limited to the Chinese Center for Disease Control and Prevention, Beijing, China.

https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/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

4. Justification for Less than Maximum Competition Eligibility for this NOFO is limited to the Chinese Center for Disease Control and Prevention (China CDC), Beijing, China. China CDC is the only public health research institute in China with advanced capacity to perform the laboratory and epidemiologic studies and analyses needed for the evaluation of Asian influenza A (H7N9) and other seasonal, epidemic and pandemic strains of influenza in China. To effectively address the domestic and global threat posed by new and emerging influenza virus strains in circulation in this part of the world, the research objectives for this study must be carried out in China. China is the only country with Asian influenza A (H7N9), a novel influenza virus with high pandemic potential. China CDC is the only national country institution with sufficient infrastructure to perform the scope of the proposed epidemiologic studies on novel and emerging influenza virus strains in China. As the premier public health institution in China, China CDC is the most appropriate and only national agency qualified to conduct the public health activities specified in the NOFO.

Country Location and Institutional Capacity

The objectives of this NOFO can only be accomplished if performed in China because China is the only source of A (H7N9), a novel influenza virus with high pandemic potential. Of global concern are the surrounding emerging influenza strains and the pandemic potential posed from genetic evolution of the highly pathogenic avian influenza viruses A (H5N1) and the reassortant virus A (H7N9).

China CDC maintains partnerships with multiple local and global academic and public health institutions and has collaborated with the US Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD), Influenza Division on influenza disease detection, prevention, and control for over 20 years. China CDC houses one of the world's six World Health Organization (WHO) Collaborating Centers for Influenza and is the WHO Influenza Collaborating Center serving the Western Pacific Region.

The more than two-decade collaboration between CDC's Influenza Division and China CDC has been invaluable to domestic and global disease control; more than 39 peer-reviewed influenza publications have been produced and have guided influenza policy.

China CDC has reliable and established systems for sharing global public health information with CDC and the Global Influenza Surveillance and Response System at WHO that are essential for adequate disease surveillance and control.

China CDC is the national public health agency for China, making it uniquely positioned to perform public health program evaluations and research studies to assess the impact and benefit of influenza vaccination in WHO-identified high risk populations. Results from this work are necessary to effectively inform pandemic risk and national influenza vaccination strategies to reduce morbidity and mortality.

Public Health Surveillance and Laboratory Capacity

China CDC has well-established public health surveillance systems to identify new human infections from novel influenza viruses and to identify seasonal and epidemic disease. For example, China CDC conducts studies to characterize novel influenza viruses, including influenza A (H5N1) and A (H7N9), in poultry and humans, provides surveillance among live bird market workers, and gathers information on changes in disease patterns, risk factors and circulating viruses; all capacities critical for the success of the NOFO's objectives.

China CDC has important and relevant laboratory capacities, including the use of sophisticated genetic next-generation sequencing, and candidate vaccine virus production, to detect and assess the risk of novel influenza viruses in poultry and humans.

China CDC has, in place, the central, provincial and district-based infrastructure required to immediately engage in the activities listed in this announcement; this should result in more rapid implementation of live-saving interventions.

China CDC is the key governmental agency that will enable US CDC to execute its global influenza strategy. Specifically, the US CDC, working through its strong partnership with China CDC, will assure the implementation and evaluation of influenza research programs that will result in the prevention and control of influenza in China, the region and the world. For example, the research findings from the current collaboration between CDC and China CDC have contributed to China's policy for influenza vaccines for vulnerable populations and the expansion of influenza vaccine programs among children and older adults.

In summary, the past collaborations between the US CDC Influenza Division and China CDC have established a research coalition and infrastructure that is optimally conducive to performing the studies needed to support applied research and surveillance for better defining the risk of novel and seasonal influenza virus infections in humans and animals, as outlined in the NOFO. Disapproval of this single source justification would erase the benefits derived from the time, effort and funds expended during previous collaborations and would create a gap in available infection control data needed to prevent and control the spread of highly pathogenic avian influenza. Spread of the highly pathogenic avian influenza virus would result in significant morbidity and mortality among US and international populations and global travelers.

5. Responsiveness Applications submitted under this notice of funding opportunity must not include activities that overlap with simultaneously-funded research or non-research projects already awarded, regardless of the funding source.

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

(Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https://eportal.nspa.nato.

int/AC135Public/Docs/US%20Instructions%2 0for%20NSPA%20NCAGE.pdf

System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, https://www.sam.gov/portal/SAM/#1.

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes. The “one-time” registration process will take three to five days to complete. However, it is best to start the registration process at least two weeks prior to application submission.

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

7. Universal Identifier Requirements and System for Award Management (SAM) All applicant organizations must obtain a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number is a nine-digit number assigned by Dun and Bradstreet Information Services. An AOR should be consulted to determine the appropriate number. If the organization does not have a DUNS number, an AOR should complete the US D&B D-U-N-S Number Request Web Form or contact Dun and Bradstreet by telephone directly at 1-866-705-5711 (toll-free) to obtain one. A DUNS number will be provided immediately by telephone at no charge. Note this is an organizational number. Individual Program Directors/Principal Investigators do not need to register for a DUNS number.

Additionally, all applicant organizations must register in the System for Award Management (SAM). Organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later.

SAM is the primary registrant database for the Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient.

Additional information about registration procedures may be found at the SAM internet site at https://www.sam.gov/index.html.

If an award is granted, the recipient 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 recipient 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.

https://www.sam.gov/portal/SAM/%231 https://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 https://www.Grants.gov http://fedgov.dnb.com/webform http://fedgov.dnb.com/webform https://www.sam.gov/index.html

9. Cost Sharing This FOA does not require cost sharing as defined in the HHS Grants Policy Statement (http://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf).

10. Number of Applications As defined in the HHS Grants Policy Statement,(https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf), applications received in response to the same Notice of Funding Opportunity 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 NOFO 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 Office of Grants Services (OGS) Technical Information Management Section (TIMS) staff at (770) 488-2700 or ogstims@cdc.gov for further instructions. Hours: Monday - Friday, 7am – 4:30pm U.S. Eastern 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 https://grants.nih.gov/grants/how-to-apply-application-guide/forms-e/general-forms-e.pdf and here: https://apply07.grants.gov/apply/forms/sample/SF424B-V1.1.pdf, except where instructed in this Notice of Funding Opportunity 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 NOFO 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 NOFO. Follow the instructions in the SF 424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, additional data required by the agency for a complete application.

While these are not identical to the PHS398 application form pages, the PHS398 reference is used to distinguish these additional data requirements from the data collected in the SF424 (R&R) components. A complete application to CDC will include SF424 (R&R) and PHS398 components. These forms can be downloaded from http://grants.nih.gov/grants/forms.htm http://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf https://www.Grants.gov mailto:pgotim@cdc.gov https://grants.nih.gov/grants/how-to-apply-application-guide/forms-e/general-forms-e.pdf%20 https://apply07.grants.gov/apply/forms/sample/SF424B-V1.1.pdf http://grants.nih.gov/grants/forms.htm

Duplication of Efforts Applicants are responsible for reporting if this application will result in programmatic, budgetary, or commitment overlap with another application or award (i.e. grant, cooperative agreement, or contract) submitted to another funding source in the same fiscal year.

Programmatic overlap occurs when (1) substantially the same project is proposed in more than one application or is submitted to two or more funding sources for review and funding consideration or (2) a specific objective and the project design for accomplishing the objective are the same or closely related in two or more applications or awards, regardless of the funding source. Budgetary overlap occurs when duplicate or equivalent budgetary items (e.g., equipment, salaries) are requested in an application but already are provided by another source.

Commitment overlap occurs when an individual’s time commitment exceeds 100 percent, whether or not salary support is requested in the application. Overlap, whether programmatic, budgetary, or commitment of an individual’s effort greater than 100 percent, is not permitted.

Any overlap will be resolved by the CDC with the applicant and the PD/PI prior to award.

Report Submission: The applicant must upload the report in Grants.gov under “Other Attachment Forms.” The document should be labeled: "Report on Programmatic, Budgetary, and Commitment Overlap.”

3. Letter of Intent Due Date for Letter of Intent: 01/23/2018

The letter of intent should be sent to:

Gregory Anderson, MPH, MS Extramural Research Program Office Office of the Associate Director of Science National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention Centers for Disease Control and Prevention U.S. Department of Health and Human Services 1600 Clifton Road, MS E-60 Atlanta, GA 30333 Telephone: 404-718-8833 Fax: 404- 718-8822 Email: GAnderson@cdc.gov

4. Required and Optional Components A complete application has many components, both required and optional. The forms package associated with this NOFO in Grants.gov includes all applicable components for this NOFO, 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 Notices of Funding Opportunities(NOFOs). Specifically, some of the following 16 components are for Resubmissions or Revisions only. See the SF 424 (R&R) Application Guidehttps://grants.nih.gov/grants/how-to-apply-application-guide/forms-e/general-forms-e.pdf and here: https://apply07.grants.gov/apply/forms/sample/SF424B-V1.1.pdf for additional information. Please attach applicable sections of the following Research Plan components as directed in Part 2, Section 1 (Notice of Funding Opportunity Description).

Follow the page limits stated in the SF 424 (R&R) unless otherwise specified in the NOFO. As applicable to and specified in the NOFO, 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 NOFO.

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.

https://grants.nih.gov/grants/how-to-apply-application-guide/forms-e/general-forms-e.pdf%20 https://grants.nih.gov/grants/how-to-apply-application-guide/forms-e/general-forms-e.pdf%20 https://apply07.grants.gov/apply/forms/sample/SF424B-V1.1.pdf

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 (R&R) Application Guide unless otherwise specified in the NOFO. All instructions in the SF424 (R&R) Application Guide https://grants.nih.gov/grants/how-to-apply-application-guide/forms-e/general-forms-e.pdf and here:

https://apply07.grants.gov/apply/forms/sample/SF424B-V1.1.pdf must be followed along with any additional instructions provided in the NOFO.

Applicants that plan to collect public health data must submit a Data Management Plan (DMP) in the Resource Sharing Plan section of the PHS 398 Research Plan Component of the application. A DMP is required for each collection of public health data proposed. Applicants who contend that the public health data they collect or create are not appropriate for release must justify that contention in the DMP submitted with their application for CDC funds.

The DMP may be outlined in a narrative format or as a checklist but, at a minimum, should include:

• Descriptions of the data to be produced in the proposed project

• How access will be provided to the data (including provisions for protection of privacy, confidentiality, security, intellectual property, or other rights)

• Use of data standards that ensure all released data have appropriate documentation that describes the method of collection, what the data represent, and potential limitations for use

• Plans for archival and long-term preservation of the data, or explaining why long-term preservation and access cannot be justified Examples of DMPs may be found here: University of California…