foa ps13-001 final 11.26.12.doc

Table of Contents

1SUBMISSION CHECKLIST TO ACCOMPANY FIRST SUBMISSION OF RESEARCH FUNDING OPPORTUNITY ANNOUNCEMENT (FOA)

6Part 1. Overview Information

8Key Dates

10Required Application Instructions

10Executive Summary

11Part 2. Full Text

11Section I. Funding Opportunity Announcement Description

13Section II. Award Information

15Section III. Eligibility Information

19Section IV. Application and Submission Information

26Section V. Application Review Information

31Section VI. Award Administration Information

41Section VII. Agency Contacts

42Section VIII. Other Information

Part 1. Overview Information

Funding Opportunity Announcement Type

New

Key Dates

Publication Date November 26, 2012

To receive notification of any changes to CDC-RFA-PS-13-001, 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.

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).

Expiration Date

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 Natural History and Prevention of Viral Hepatitis Among Alaska Native Persons FOA has two principal aims: 1) to improve efforts to prevent hepatitis A and B through vaccination and 2) to study interventions to reduce mortality and morbidity from chronic hepatitis B and C. Mechanism of Support. Cooperative Agreement.

Funds Available and Anticipated Number of Awards. Estimated total funding available including direct and indirect costs for first year (12 month budget period): $300,000

Estimated total funding available including direct and indirect costs for entire project period ( 5 year project period): $1,500,000. Awards issued under this FOA are contingent upon availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed research will vary from application to application, it is also anticipated that the size and duration of each award may also vary. The total amount awarded and the number of awards will depend upon the number, quality, duration and cost of the applications received.

Budget and Project Period. Estimated total funding available including direct and indirect costs for first year (12 month budget period): $300,000.

Estimated total funding available including direct and indirect costs for entire project period (5 year project period) $15,000,000. The project period will run from 06/30/2013 to 06/29/2018.

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

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

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. NOTE: CDC does not make awards to individuals directly. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply. Number of PDs/PIs. State the authoritative structure you expect to see in submitted applications.

Number of Applications. Eligible applicant institutions may only submit one application.

Application Type. New - An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round. (Type 1) Special Date(s). Program should insert dates for any planned technical assistance conference calls or other special dates.

Application Materials. See Section IV.1 for application materials.

Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (770) 488-2783.

Part 2. Full Text

Section I. Funding Opportunity Announcement Description

Statutory Authority

This program is authorized under Sections 317(k)(2) and 318B of the Public Health Service Act (42 U.S.C. 247(k)(2)

1. Background and Purpose Hepatitis A is a disease caused by the hepatitis A virus (HAV). Person-to-person transmission through the fecal-oral route is the primary means of HAV transmission. Hepatitis A epidemiology in the United States has fundamentally changed with the licensure of hepatitis A vaccine and implementation of national Advisory Committee on Immunization Practices (ACIP) recommendations for its use. Before the use of hepatitis A vaccine, rates among Alaska Native persons were more than five times higher than rates in other racial/ethnic populations. Data are needed to determine the antibody persistence provided by hepatitis A vaccine and the possible need for a booster dose.

Hepatitis B is a disease caused by the hepatitis B virus (HBV), which is transmitted through percutaneous exposure to infectious blood or body fluids. HBV can cause chronic infection, resulting in cirrhosis of the liver, liver cancer, liver failure, and death. Hepatitis B vaccine is the most effective measure to prevent HBV infection and its consequences.

To date, hepatitis B immunization strategies for infants, children and adolescents have been implemented with considerable success. Questions remain about the duration of protection after primary vaccination with hepatitis B vaccine (long-term effectiveness) and whether or not vaccinated persons will require booster doses of vaccine to maintain protection against HBV infection in the future. These questions are of particular importance for persons who initiated hepatitis B vaccination at birth, as recent data suggest that a greater proportion of persons vaccinated as newborns will lose protective antibody compared with those vaccinated as children or adults. Universal infant hepatitis B vaccination was begun in 1992; therefore, many persons vaccinated at birth are now reaching adulthood where the risk of exposure to HBV will increase (e.g., as the result of occupational or sexual exposure).

Historically, HBV infection was endemic among Alaska Native persons. Although hepatitis B incidence has declined dramatically as successive cohorts of Alaska Native persons have been vaccinated in infancy, childhood and as adults, there remain a substantial number of Alaska Native persons already infected with HBV who remain at risk for complications of the infection.

Chronic liver disease due to etiologies other than chronic HBV infection causes substantial morbidity and mortality among Alaska Native persons. Other causes of chronic liver disease in this population include chronic hepatitis C, alcohol-related liver disease and non-alcoholic fatty liver disease, and autoimmune hepatitis.

The Natural History and Prevention of Viral Hepatitis Among Alaska Native Persons FOA has two principal aims: 1) to improve efforts to prevent hepatitis A and B through vaccination and 2) to study interventions to reduce mortality and morbidity from chronic hepatitis B and C.

Health Equity - The program supports efforts to improve the health of populations disproportionately affected by HIV/AIDS, viral hepatitis, STDs and TB by maximizing the health impact of public health services, reducing disease prevalence, and promoting health equity consistent with the National HIV/AIDS Strategy available at http://www.whitehouse.gov/administration/eop/onap/nhas.

Health disparity is a particular type of health difference that is closely linked with social or economic disadvantage based on their racial or ethnic group, religion, socioeconomic status, gender, mental health, cognitive, sensory, or physical disability, sexual orientation, geographic location, or other characteristics historically linked to discrimination or exclusion. [HP 2020- http://www.healthypeople.gov/hp2020/advisory/PhaseI/glossary.htm] Health disparities in HIV, viral Hepatitis, STDs, and TB are inextricably linked to a complex blend of social determinants that influence which populations are most severely affected by these diseases.

Social determinants are the economic and social conditions that influence the health of individuals, communities and jurisdictions and include conditions for early childhood development; education, employment, and work; food security, health services, housing, income, and social exclusion.

Health equity is a desirable goal that entails special efforts to improve the health of those who have experienced social or economic disadvantage. It requires:

· Continuous efforts focused on elimination of health disparities, including disparities in health and in the living and working conditions that influence health, and

· Continuous efforts to maintain a desired state of equity after particular health disparities are eliminated.

Programs should use data, including social determinants data, to identify communities within their jurisdiction that are disproportionately affected by HIV, viral hepatitis, STDs and TB and related diseases and conditions, and plan activities to help eliminate health disparities. In collaboration with partners and appropriate sectors of the community, programs should consider social determinants of health in the development, implementation, and evaluation of program specific efforts and use culturally appropriate interventions that are tailored for the communities for which they are intended.

Healthy People 2020 and other National strategic priorities – The National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) of CDC within HHS is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2020" and to measuring program performance as stipulated by the Government Performance and Review Act (GPRA). This RFA addresses “Healthy People 2020” priority area(s) of Immunization and Infectious Diseases and is in alignment with National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention performance goal(s) to protect Americans from Infectious Diseases. Additional information is available at www.healthypeople.gov.

Public Health Impact - Worldwide, there are limited sources of data available for the study of long-term protection afforded by hepatitis A and B vaccines, as well as for the long-term follow-up of population-based cohorts for examining the natural history, epidemiology, and treatment of chronic HBV and HCV infections. There remains a continuing need for hepatitis vaccination data to ensure that populations at risk for HAV and HBV exposure remain protected for as long as possible after primary immunization, and to determine whether booster doses are necessary to maintain protection. With the ongoing development and release of new antiviral medications for HBV and HCV infection, the treatment of persons with chronic hepatitis B and C is currently an area of intensive research. Data regarding optimal treatment regimens are urgently needed to prevent the long-term sequelae of infection (i.e., cirrhosis, liver cancer), to minimize the risk of transmission of virus from infected to non-infected persons, and to prevent the emergence of drug resistance. Improvements in treatment will reduce hepatitis-related mortality from cirrhosis and liver cancer, reduce the need for liver transplantation, reduce the need for hospitalization related to complications of chronic liver disease, and improve overall quality of life.

2. Approach- This FOA supports efforts to improve the health of U.S. populations, including Alaska native persons, disproportionately affected by hepatitis by maximizing public health impact and relevancy of public health services through research of hepatitis vaccinination outcome and efficacy . Health inequities are closely linked with social or economic disadvantage and health disparities in viral hepatitis are inextricably linked to a complex blend of social determinants. Health equity is a desirable goal that entails special efforts to improve the health of those who have experienced social or economic disadvantage. CDC Programs use data, including social determinants data, to identify and study communities that are disproportionately affected by viral hepatitis and plan activities to help eliminate disparities. Through collaboration and cooperative assistance partnerships with public health programs and community sectors, appropriate interventions can be tailored for the disparate populations and public benefit.

Objectives/Outcomes- Each of the following research objectives must be addressed by the applicant in the research plan of the application to be considered for funding:

· Evaluate the antibody persistence after hepatitis A vaccination among Alaska Native persons who received the two-dose primary vaccine series as infants (< 2 years of age) and young children.

· Perform a retrospective review of acute hepatitis A cases for vaccine history to estimate vaccine efficacy at various time periods after vaccination. Of interest would be vaccine failure after 1 dose versus 2 doses of the primary vaccination regimen.

· Evaluate the long term protection afforded by plasma-derived and recombinant hepatitis B vaccines among Alaska Native persons who received the primary vaccine series 20-30 years ago. Examples would include, but are not limited to, a study of long-term immunity of young adult healthcare workers or health professional students who were vaccinated at birth with recombinant hepatitis B vaccine.

· Perform a retrospective review of acute hepatitis B cases for vaccine history to estimate vaccine efficacy at various time periods after vaccination. Of interest would be vaccine failure among persons vaccinated at birth versus those who received primary vaccination in childhood or adulthood.

· Demonstrate through letters of support or by previous publications or conference abstracts, immediate access to sufficiently large cohorts (a total of at least 100 people) of Alaska Native persons who, as infants and young children, started the hepatitis A vaccine series before 2 years of age and between 2 and 12 years of age. These cohorts should include a minimum of one cohort in each age category (i.e., a total of two cohorts) that received the primary hepatitis A vaccine series 15 or more years ago, in which response to vaccination was verified by post-vaccination serologic testing.

· Demonstrate through letters of support or by previous publications or conference abstracts, immediate access to a sufficiently large cohort (a total of at least 100 people) of Alaska Native persons who, as infants, young children and adults, received complete hepatitis B vaccine series. These cohorts should include persons that received the primary hepatitis B vaccine series 20 or more years ago, in which response to vaccination was verified by post-vaccination serologic testing.

· Applicants should demonstrate in their application the existence of a well-established cohort or registry of Alaska Native persons with chronic HBV infection and access to their medical record data, as documented by letters of support or by previous publications or conference abstracts.

· To study the natural history and medical management of chronic hepatitis B and hepatitis C using an established registry or cohort of Alaska Native persons and data from their medical records followed over time.

· Evaluate persons in the chronic hepatitis B and C cohort or registry for other risk factors for chronic liver disease, including alcohol-related liver disease by determining the prevalence of alcohol use and systematically quantifying the volume consumed.

· Determine mortality from chronic liver disease among persons in the chronic hepatitis B and C cohort or registry by obtaining death certificate data.

Target population - Alaska Natives, to include persons:

· who, as infants and young children, started the hepatitis A vaccine series before 2 years of age and between 2 and 12 years of age

· who, as infants and young children, started the hepatitis A vaccine series before 2 years of age and between 2 and 12 years of age received complete hepatitis B vaccine series

· with chronic HBV and HCV infection and access to their medical record data Collaboration/Partnerships -

· Eligible applicants will have close linkages and collaborations with an Alaska Native Tribal Health Consortium or similar organization that provides for and manages statewide health services for Alaska Area Native persons documented by letters of support from these agencies or they may not be funded.

Evaluation/Performance measurement – Grantee progress will be evaluated periodically based on the following accomplishments and criteria, as indicated by study design and protocol:

· Identification and recruitment of target study population.

· Development and implementation of research study protocols and consent forms necessary to support the research study.

· Obtain appropriate approvals from required Institutional Review Board(s), tribal review committees, and other relevant cooperating institutions participating in the research project.

· Ability to provide serum samples to CDC, as appropriate.

· Collection and recording of data into an appropriate statistical database for analysis.

· Collaboration with CDC to conduct appropriate data analysis and interpretation.

· Collaboration with CDC in all stages of the research, including study design, data analysis, and sharing data and results with CDC. This includes, but is not limited to, active participation in conference calls, webinars, and in-person meetings (i.e. grantee meetings and special project meetings)

· Clearance of all abstracts and manuscripts with CDC prior to submission in accordance with established CDC clearance procedures.

· Progress toward completion of proposed research projects, given they can be feasibly completed within the two year award period.

· Projects that involve the collection of information from 10 or more individuals/entities and are funded by a grant/cooperative agreement will be subject to review and approval by the Office of Management and Budget (OMB) under the Paperwork Reduction Act.

Translation plan – The PI should describe how the findings from this study may be used to promote, enhance, or advance translation of the research to policy or practice. This section should be understandable to a variety of audiences, including policy makers, practitioners, public health programs, healthcare institutions, professional organizations, community groups, researchers, and other potential users. The PI should identify the research findings that were translated into public health policy or practice and how the findings have been or may be adopted in public health settings. Or, if they cannot be applied yet, this section should address which research findings may be translated, how these findings can guide future research or related activities, and recommendations for translation. If relevant, describe how the results of this project could be generalized to populations and communities outside of the study. Questions to consider in preparing this section include:

· How will the scientific findings be translated into public health policy or practice?

· How will the project improve or effect the translation of research findings into policy or practice?

· How will the research findings help promote or accelerate the dissemination, implementation, or diffusion of improvements in public health programs or practices?

· How will the findings advance or guide future research efforts or related activities?

Section II. Award Information

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round.

Funds Available and Anticipated Number of Awards

Year 1: $300,000

Year2: $300,000

Year 3: $300,000

Year 4: $300,000

Year 5: $300,000

List anticipated number of awards here: 1

Estimated total funding available including direct and indirect costs for first year(12 month budget period): $300,000

Estimated total funding available including direct and indirect costs for entire project period( 5 year project period): $1,500,000

Floor amount of $100,000 (total costs). This floor is for the first 12 month budget period.

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

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

Section III. Eligibility Information

1. Eligible Applicants Alaska Native Tribal Health Consortium

Roald Helgesen, Chief Executive Officer

4000 Ambassador Drive

Anchorage, AK 99508

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

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

For this announcement, applicants may not include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Justification for Less than Maximum Competition: Date of approval 9/27/2012. Collaborative research on viral hepatitis in Alaska Native persons between CDC (the Division of Viral Hepatitis [DVH] and the Arctic Investigations Program) and the Alaska Native Health Service began in 1973. The history of collaboration between DVH and what is now the Alaska Native Tribal Health Consortium (ANTHC) has been long and fruitful, resulting in scientific publications that have had a dominant role in shaping public health policy and clinical management guidelines for nearly four decades.

Continuation of this relationship with ANTHC is critical as it is the only institution in the world capable of continuing the landmark studies of Alaska Native persons that are essential to the formulation of U.S. and global hepatitis A and hepatitis B vaccination policy, as expressed in vaccination guidelines issued by the Advisory Committee on Immunization Practices, the Infectious Diseases Society of America, and the World Health Organization. ANTHC is the sole entity that has access to the clinical and vaccination records of the specific patient/study participants that are indispensable for continuing this research. Furthermore, ANTHC oversees the largest cohort of Alaska Native persons with chronic hepatitis B and C who undergo regular follow-up and who receive care through a unified health system. The unique access of ANTHC to the electronic data of these study subjects enables reliable, population-based longitudinal follow-up data unavailable elsewhere in the world. As such, ANTHC is uniquely qualified to complete the research aims intended in the FOA.

4. Responsiveness: Not Applicable

5. Required Registration 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: http://www.dlis.dla.mil/Forms/Form_AC135.asp

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

· Grants.gov

· eRA Commons

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

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

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

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

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

7. 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.

8. Cost Sharing

This FOA does not require cost sharing as defined in the HHS Grants Policy Statement (http://dhhs.gov/asfr/ogapa/aboutog/grantsnet.html).

9. Number of Applications

Only one application per institution (normally identified by having a unique DUNS number) is allowed As defined in the HHS Grants Policy Statement, (http://dhhs.gov/asfr/ogapa/aboutog/grantsnet.html), applications received in response to the same funding opportunity announcement generally are scored individually and then ranked with other applications under peer review in their order of relative programmatic, technical, or scientific merit. HHS/CDC will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Section IV. Application and Submission Information

1. Address to Request Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity from www.Grants.gov.

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

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/guide/url_redirect.htm?id=12000), except where instructed in this Funding Opportunity Announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, additional data required by the agency for a complete application. While these are not identical to the PHS398 application form pages, the PHS398 reference is used to distinguish these additional data requirements from the data collected in the SF424 (R&R) components. A complete application to CDC will include SF424 (R&R) and PHS398 components. These forms can be downloaded and uploaded as Attachment A from the following link: http://www.cdc.gov/od/pgo/funding/grants/foamain.shtm

3. 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.

4. PHS 398 Research Plan Component The SF424 (R&R) Application Guide includes instructions for applicants to complete a PHS 398 Research Plan that consists of 16 components. Not all 16 components of the Research Plan apply to all Funding Opportunity Announcements (FOAs). Specifically, some of the following 16 components are for Resubmissions or Revisions only. See Part I, Section 5.5 of the SF 424 (R&R) Application Guide (http://grants.nih.gov/grants/guide/url_redirect.htm?id=12000) for additional information. Please attach applicable sections of the following Research Plan components as directed in Part 2, Section 1 (Funding Opportunity Announcement Description). Follow the page limits stated in the SF 424 unless otherwise specified in the FOA. As applicable to and specified in the FOA, the application should include the bolded headers in this section and should address activities to be conducted over the course of the entire project, including but not limited to:

1. Introduction to Application (for Resubmission and Revision ONLY) - provide a clear description about the purpose of the proposed research and how it addresses the specific requirements of the FOA.

2. Specific Aims – state the problem the proposed research addresses and how it will result in public health impact and improvements in population health.

3. Research Strategy – the research strategy should be organized under 3 headings: Significance, Innovation and Approach. Describe the proposed research plan, including staffing and timeline.

4. Inclusion Enrollment Report (Renewal and Revision applications ONLY)

5. Progress Report Publication List (for Continuation ONLY) Human Subjects Section

6. Protection of Human Subjects

7. Inclusion of Women and Minorities

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

9. Inclusion of Children

Other Research Plan Sections

10. Vertebrate Animals

11. Select Agent Research

12. Multiple PD/PI Leadership Plan.

13. Consortium/Contractual Arrangements

14. Letters of Support

15. Resource Sharing Plan(s)

16. Appendix

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

All instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Adobe_VerB.pdf) must be followed along with any additional instructions provided in the FOA.

5. 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.

6. 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 100 pages for all appendices.

7. 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/guide/url_redirect.htm?id=12000).

8. Submission Dates and Times

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

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

If errors are found, the applicant will be notified in the eRA Commons. They must make required changes to the local copy of their application and submit again through Grants.gov. Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

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

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

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

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

Applicants are strongly encouraged to allocate additional time prior to the submission deadline to submit their applications and to correct errors identified in the validation process. Applicants are encouraged also to check the status of their application submission to determine if the application packages are complete and error-free. Applicants who encounter system errors when submitting their applications must attempt to resolve them by contacting the Grants.gov Contact Center (1-800-518-4726; support@grants.gov). If the system errors cannot be resolved, applicants must contact CDC PGO TIMS at 770-488-2700; www.pgotim@cdc.gov for guidance at least 3 calendar days before the deadline date.

After submission of your application package, applicants will receive a “submission receipt” email generated by Grants.gov. Grants.gov will then generate a second e-mail message to applicants which will either validate or reject their submitted application package. This validation process may take as long as two (2) business days. A third and final e-mail message is generated once the applicant’s application package has passed validation and the grantor has confirmed receipt of the application.

Unsuccessful Submissions:

If an application submission was unsuccessful, the applicant must:

1. Track his/her submission and verify the submission status (tracking should be done initially regardless of rejection or success).

a. If the status states “rejected,” do #2a or #2b.

2. Check his/her emails from both Grants.gov and eRA Commons for rejection notices.

a. If the deadline has passed, he/she should email the Grant Management Specialist listed in the FOA (pgotim@cdc.gov) explaining why the submission failed.

b. If there is time before the deadline, he/she should correct the problem(s) and resubmit as soon as possible.

9. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review (http://grants.nih.gov/grants/guide/url_redirect.htm?id=11142).

10. 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.

11. 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. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically (http://grants.nih.gov/grants/guide/url_redirect.htm?id=11144).

Important reminders:

All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to CDC.

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

Applicants are reminded to enter the approved Federal Wide Assurance (FWA) that the applicant has on file with the Office for Human Research Protections, if available. If the applicant has a FWA number, enter the 8-digit number. Do not enter the 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 this 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/ElectronicReceipt/avoiding_errors.htm or http://grants.nih.gov/grants/ElectronicReceipt/submit_app.htm Upon receipt, applications will be evaluated for completeness by the CDC Procurement and Grants Office (PGO) and responsiveness by PGO and the Center, Institute or Office of the CDC. Applications that are incomplete and/or nonresponsive will not be reviewed.

Section V. Application Review Information

1. Criteria

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

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Are the study activities likely to provide data on the persistence of antibody from hepatitis A vaccine 15 years or more after primary vaccination among persons vaccinated in early childhood? Are the study activities likely to provide data on the long-term effectiveness of hepatitis B vaccine 20 years or more after primary vaccination among persons vaccinated at birth, in childhood, and adulthood, taking into consideration prenatal and perinatal infection?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the project? Have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Are the investigators experienced in conducting research with Alaska Native populations? Are the investigators experienced in conducting evaluation of antibody persistence provided by hepatitis A vaccine and long-term hepatitis B vaccine effectiveness studies among Alaska Native persons? Do the investigators have experience in obtaining Institutional Review Board (IRB) approval for studies conducted with an Alaska Native Tribal Health Consortium or similar organization that provides for and manages statewide health services for Alaska Area Natives?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Do they provide data that represent progress in the field of long-term antibody persistence following hepatitis A vaccination by providing follow-up of 15 or more year’s duration since primary vaccination? Do the proposed studies provide data that represent progress in the field of long-term hepatitis B vaccine effectiveness by providing follow-up of 20 or more year’s duration since primary vaccination?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and provide reasonable assurance of successful accomplishment of the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Does the applicant present sound methods for evaluation of antibody persistence after hepatitis A vaccination and long term hepatitis B vaccine effectiveness? Does the applicant describe access to an established cohort that received the primary hepatitis A vaccine series 15 or more years ago in early childhood, in which response to vaccination was verified by post-vaccination serologic testing? Is there sufficient sample size to allow conclusions to be generalized? Does the applicant describe an established cohort to which the applicant has access that received the primary hepatitis B vaccine series 20 or more years ago at birth, in early childhood, childhood, and adulthood in which response to vaccination was verified by post-vaccination serologic testing? Does the applicant provide evidence of a history of work in long term effectiveness of hepatitis B vaccine among Alaska Native persons by peer reviewed publications? For the desirable research objective, does the applicant provide data on an existing cohort or registry of Alaska Native patients with chronic hepatitis B including data on demographics, extent of liver disease as demonstrated by laboratory tests or clinical events, and history of evaluation for and completion, if applicable, of treatment? For the desirable research objective, does the applicant demonstrate that the cohort or registry of Alaska Native patients with chronic HBV infection to be studied is population-based? For the desirable research objective, does the applicant provide data on an existing cohort or registry of Alaska Native patients with chronic hepatitis C including data on demographics, extent of liver disease as demonstrated by laboratory tests or clinical events, and history of evaluation for and completion, if applicable, of treatment?