NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). 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. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

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

The purpose of this Funding Opportunity Announcement (FOA) is to facilitate the design, conduct and completion of clinical trials for improving prevention of HPV-related cancers in HIV-infected individuals. Through this FOA, the National Cancer Institute (NCI) will support a network of international collaborative sites conducting meritorious and appropriately designed prevention clinical trials in the Latin American and Caribbean (LAC) region via a U54 Partnership Centers mechanism. Each proposed U54 Partnership Center must be based on a collaboration between a research institution in the United States (as the applicant institution) and partnering institution(s) in low- and middle-income countries (LMICs) in the LAC region. The proposed clinical trials should be focused on optimizing clinical prevention interventions among HIV-infected individuals, including immunoprevention (vaccination), screening and triage, and precancer treatment.

Each Partnership Center application must propose a Clinical Trials Program to develop and conduct three prevention clinical trials within the 5-year project period. As infrastructure supporting the Clinical Trials Program, each Partnership Center should include an Administrative and Coordinating Core, a Data Management and Statistical Core, and a Central Laboratory Core. Results of the clinical trials conducted through the Partnership Centers are expected to inform improvements in preventive clinical care and reduce the burden of highly preventable HPV-related cancers in HIV-infected individuals

The FOA will be open to all qualified applicants from U.S. institutions with pre-existing or newly formed collaborations with counterparts in the LAC region. The applicant and collaborating institutions must be able to demonstrate a successful track record of collaborative international clinical research and/or clinical collaborative activities in the LAC region. Research conducted through this initiative will seek to utilize and build on infrastructures developed through these activities for conducting clinical trials of relevance to the NIH HIV/AIDS research agenda (NOT-OD-15-137) as well as clinical and public health research priorities in LMICs. The Partnership Centers funded through this FOA are expected to enhance the evidence base for innovative clinical interventional approaches for preventing HPV-related cancers among HIV-infected individuals, gaining biologic insights into viral-host interactions and immunologic contributions to cancer development, and ultimately informing improvements in clinical care options for HIV-infected individuals globally.

Key Terms and Definitions for this FOA:

Latin American and Caribbean (LAC) region: In the context of this FOA, the LAC region refer to all countries referred as being in the Latin American and Caribbean region in the World Bank classification system http://data.worldbank.org/about/country-classifications/country-and-lending-groups

Low- and Middle-Income Countries (LMICs): In the context of this FOA, LMICs refer to countries classified according to Gross National Income (GNI) per capita as low-income, lower-middle-income, and upper-middle-income in the World Bank classification system http://data.worldbank.org/about/country-classifications/country-and-lending-groups.

Clinical trials: The NIH has clarified its definition of a clinical trial in NOT-OD-15-015. A clinical trial is defined as 'research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes'.

High- and Medium-Priority topics for HIV/AIDS research:

The NIH has developed a series of guidelines for determining whether a research project has a high-, medium-, or low-priority for receiving AIDS-designated funding. These guidelines do not assess/determine the scientific and technical merit of a project, only the priority for receiving AIDS-designated funds. A description of these priority topics and examples of each are provided in NOT-OD-15-137.

The HIV/AIDS epidemic continues to pose a major global disease burden, with over 30 million individuals infected worldwide, of whom more than 90% reside in low- and middle-income countries. Those individuals are increasingly accessing affordable combination antiretroviral therapy for treatment of HIV infection. Patients receiving such therapy are living longer and have a decreased incidence of certain AIDS-defining cancers associated with very low CD4 counts (e.g., Kaposi Sarcoma, non-Hodgkin lymphoma). However, there are also consequent increased risks for other malignancies, especially cancers that are etiologically-linked to HPV, including cervical, vulvar, vaginal, anal, and oropharyngeal cancers. These HPV-related cancers remain a leading cause of mortality and morbidity among HIV-infected individuals in LMICs. The availability, over the past decade, of highly effective prophylactic HPV vaccines offers an unprecedented opportunity for primary prevention for these cancers. Furthermore, screening for and treating women with precancerous lesions is a highly effective and well-known strategy for secondary prevention of cervical cancer. Approaches for screening for other HPV-related cancers (e.g., anal cancer) are still under active clinical investigation.

Protocols for prevention of HPV-related cancers in HIV-infected individuals have not been refined, particularly in the context of resource-constrained settings where traditional prevention-oriented services (e.g., periodic cervical cancer screening, or HPV vaccination) are either lacking or are sub-optimally functioning. Whereas several efforts have been undertaken to quantify the burden of HPV-associated neoplastic disease in HIV-infected populations, there have been very few efforts to generate evidence on the utility of clinical strategies to prevent such cancers. In fact, the mere availability of prevention tools or approaches (e.g., HPV vaccines, novel screening tests, non-surgical treatment strategies) does not automatically translate to guidelines for their utilization among HIV-infected individuals. Collaborative clinical trials that seek to answer outstanding research questions related to optimizing frequency and algorithms for implementation of existing and novel interventions are needed to guide evidence-based prevention and treatment strategies for persons living with HIV/AIDS.

LMIC countries in the LAC region have a high dual clinical burden of HIV/AIDS and HPV-related cancers. It is estimated that 2 million people are living with HIV in the LAC region, and about 100,000 are newly infected annually. Annual new HIV infections among adults increased by 2% in Latin America and by 9% in the Caribbean between 2010 and 2015. Nine countries in the region have generalized HIV epidemics, and most others have concentrated epidemics among their most-at-risk population subgroups including female sex workers and their clients, men who have sex with men, and injection drug users. The LAC region also has some of the highest incidence and mortality rates from cervical cancer in the world. The age-adjusted cervical cancer incidence rates range from 20 to 80 per 100,000 women per year, which is 3- to 11-times higher than in the United States. Governments in LAC countries are demonstrating stronger commitments than ever before to address burdens of both HIV/AIDS and cervical and other HPV-related cancers. Several LAC countries have led the way in creating models of HIV care for other LMICs by providing universal access to affordable antiretroviral drugs for HIV-infected individuals, along with faciliatory health care access policies towards at-risk groups, and enhanced linkages for implementation with non-governmental organizations. Recent strong commitments from LAC region governments have attempted to increase utilization of multilateral bulk procurement mechanisms such as the PAHO Revolving Fund to improve cervical cancer screening and prevention, as well as incorporation of HPV vaccination as part of national immunization programs. There are strong and well-established academic global health partnerships between US academic medical centers and LAC region country counterparts that have hosted long-established NIH-funded clinical trials infrastructures. Such settings in the LAC region that provide a highly capable clinical research workforce and infrastructure for conducting high-quality cancer prevention clinical trials within high clinical disease burden settings also provide the opportunity to demonstrate and evaluate strategies for eventual translation to other LMIC settings.

Overall Goals for the Partnership Centers:

Partnership Centers proposed in response to this FOA must be able to propose, develop, and conduct highly meritorious clinical trials focused on prevention of HPV-related cancers in HIV-infected individuals. These clinical trials must be conducted jointly by the U.S. institution and LAC region country institution at clinical sites in the partnering LAC region countries. Results of these clinical trials are expected to inform improvements in clinical cancer preventive care and reduce the burden of highly preventable HPV-related cancers in HIV-infected individuals. The proposed Partnership Centers should also enhance the ability of the partnering LAC region institution(s) to serve as a national and regional resource for clinical research in prevention of HPV-related cancers in HIV-infected individuals.

Scientific Scope and Key Requirements:

Central Research Themes.

The Clinical Trials Program of each Partnership Center is expected to develop and conduct three clinical trials that are expected to focus on one or more of the following three broad prevention science areas:

Area 1: HPV immunoprevention among HIV-infected individuals;

Area 2: Cervical cancer screening and triage approaches for HIV-infected women; and

Area 3: Evaluating non-surgical strategies for treating HPV-related precancerous lesions among HIV-infected individuals.

The trials are expected to address issues that are both high-priority to the partnering LAC and are considered high- and medium-priority HIV/AIDS research priority areas for the NIH (NOT-OD-15-137). Clinical trials may address outstanding research questions within each prevention science area, including, but not limited to, the following:

Area 1: Evaluating and optimizing HPV immunoprevention in HIV-infected individuals

• Defining the optimal timing, schedule, duration of protection, and dosing of prophylactic HPV vaccines, especially for perinatally-HIV-infected adolescents
• Evaluating the potential role of prophylactic HPV vaccines in preventing reactivation of latent HPV and preventing recurrence of HPV infections in the adjunctive post-precancer treatment setting
• Evaluating if minimal serologic titers that predict efficacy can be evaluated in the context of HIV-induced immunosuppression among HPV vaccinated individuals
• Evaluating the safety and immunogenicity of candidate therapeutic HPV vaccines in the context of reduced cellular immune response due to HIV
• Evaluating the role of novel candidate vaccines that seek to provide a combined preventive and therapeutic benefit among HIV-infected individuals

Area 2: Evaluating and optimizing Cervical Cancer Screening and Triage approaches for HIV-infected women

• Evaluating performance of primary HPV screening vis- -vis cytology/visual-based screening
• Optimizing implementation and access to cervical cancer screening for HIV-infected women via self-collection of samples for primary HPV screening
• Evaluating optimal approaches to triage for HPV positive test results, including visual (e.g., VIA/visual inspection after acetic acid wash), microscopic (e.g., reflex cytology, p16/Ki67 immunocytochemistry), or molecular (e.g., HPV E6/E7 oncoprotein testing, HPV mRNA) triage strategies.
• Evaluating optimal cut-offs of HPV assay positivity to balance sensitivity versus specificity
• Optimizing the implementation of visual screen-and-treat protocols by utilization of HPV-based diagnostics for screening or triage
• Area 3: Evaluating novel non-surgical approaches for treating HPV-related precancerous lesions among HIV-infected individuals
• Evaluating the safety and efficacy of novel locally applied agents in inducing regression of cervical and other HPV-related precancerous disease (e.g., vulvar, vaginal, anal) and clearing oncogenic HPV in HIV-infected women.
• Evaluating the safety and efficacy of chemoprevention agents approved for other indications (e.g., agents such as cidofovir, imiquimod, 5-flurouracil, carrageenan, etc. used for topical treatment genital warts or other sexually transmitted infections) that can be repurposed for non-surgical treatment of HPV-related precancerous lesions
• Evaluating the efficacy of topical drug delivery vehicles (e.g., gels/creams via intravaginal applicators, suppositories, intravaginal rings, sponges) and delivery approaches (clinician-applied or self-administered) for non-surgical treatment of HPV-related precancerous lesions
• Evaluating combinations of topical agents with therapeutic HPV vaccines to enhance the efficacy of non-surgical treatment of HPV-related precancerous lesions

The emphasis and choice of focus areas and trials should be reflective of the LAC countries' priorities, capabilities of each clinical research site s infrastructures and the available pool of potential research participants for enrollment and retention, and access to appropriate prevention intervention technologies and agents. In addition, to be responsive to this FOA, research proposed must align with one or more high or medium priority topics for AIDS research as defined in NOT-OD-15-137 (NIH HIV/AIDS Research Priorities and Guidelines for Determining AIDS Funding).

Key Requirements for this FOA:

Partnership Center Organization:

The proposed Partnership Center must be designed as a consortium of partnering institutions that will be co-led by the Program Director/Principal Investigator (PD/PI) of the U.S. applicant institution and the collaborating PD/PI at the LAC partnering institution(s).

Each proposed Partnership Center must consist of the following components:

• Administrative and Coordinating Core: This Core will be responsible for providing overall administration, coordination, communication and management including training and study monitoring, regulatory support, liaison with NCI Staff, recruitment and retention efforts, convening and liaison with data safety and monitoring boards, and facilitating career development opportunities for young investigators and trainees. The Core must also have requisite capabilities to ensure the scientific integrity, research productivity, and regulatory and fiscal responsibilities.
• Clinical Trials Program: The main scientific component of the Partnership Center must be centered on designing and conducting three prevention clinical trials focused on prevention of HPV-related cancers among HIV-infected individuals in clinical research sites based in the partnering institutions in the LAC region within the 5-year project period.
• These three trials must be directly relevant to one or more of the three priority Research Areas defined above.
• One clinical trial protocol must be a fully developed study, with adequate conceptual and implementation details for launch within the first year of the study period (presented as a 'Delayed Start Study').
• Concepts for the other two clinical trial protocols may have limited details about trial implementation known at the time of application, and could be proposed as developmental concepts, with an expectation that they may be launched in later years but completed within the 5-year project period (presented as 'Delayed Onset Study').
• The proposed clinical trial and the two exploratory trial concepts must be conceptually sound, supported by compelling underlying biological rationale and preclinical data, efficiently and effectively enroll human research subjects, feasible to be conducted and completed within available resources and timelines, and should be well integrated with the general current state of the field and relevance of clinical and public health needs in the communities in which it is being implemented in the LAC region.
• Prior to concept approvals and the actual study launch, the Clinical Trials Program should be able to finalize preparatory steps for the clinical trials (e.g., enrollment strategies, refinement of data collection instruments, staff training, etc.).
• Each clinical trial protocol will be subject to review and approval by the NCI prior to activation through the Partnership Center.
• Data Management and Statistical Core: This Core will provide technical assistance for statistical considerations in protocol design, and assist with data management, data analysis, and reporting of results and scientific publications.
• Central Laboratory Core: This Core will be responsible for conducting central pathology endpoint reviews, quality assurance for virologic/immunologic testing, and liaison with external labs for specialized biomarker assays.

Program Governance:

• Scientific coordination across the U54 Partnership Center awardees will be accomplished via a Partnership Center Coordinating Committee with representation from the Partnership Centers PD/PI and NCI staff.
• NCI will constitute a Clinical Trials Oversight Committee that will be involved in the NCI decisions about approval and initiation of individual clinical trials, oversight for the conduct of these trials, and coordination with other NCI-funded initiatives.

For details on the composition and functions of the Partnership Center Coordinating Committee and NCI Clinical Trials Oversight Committee, see Section VI.2A. Cooperative Agreement Terms and Conditions of Award.

Non-responsive applications:

Applications with the following characteristics will be considered non-responsive and will not be reviewed:

• Applications that do not propose clinical research that meets the NIH definition of clinical trials;
• Applications that are not focused on the three research areas of prevention science defined above;
• Applications proposing basic, epidemiologic, or correlative studies utilizing specimens of previously/separately conducted clinical trials (i.e., those trials that are not supported through this FOA); and
• Applications that propose ideas that do not constitute high or medium priority topics for AIDS research as defined in NOT-OD-15-137 (NIH HIV/AIDS Research Priorities and Guidelines for Determining AIDS Funding).

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Note regarding Partnerships with Foreign Institutions: Only United States (U.S.)-based institutions are eligible to apply but each application must involve a partnership with one or more Foreign institution(s) located in LMICs in the LAC region (as defined in "Key Terms for the FOA" in Section I). Institutions from High Income Countries (HIC) other than U.S. are not eligible to apply but may participate, if desirable, as additional partners.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) 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 NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

Applicants are required to use the multiple PDs/PIs option (see http://grants.nih.gov/grants/multi_pi/ for more information) and designate at least two PDs/PIs:

• The contact PD/PI must have the primary affiliation at the application-submitting U.S. institution.
• A second PD/PI must represent the partnering institution(s) in the LAC region.
• Additional PD(s)/PI(s) from US and/or LAC partnering institutions may be named in the multiple PD/PI format commensurate with their roles and responsibilities in the proposed Partnership Center application.

All individuals designated as PD(s)/PI(s) must have appropriate expertise in clinical trials related to either HIV/AIDS, oncology, infectious diseases, sexual and reproductive health, and/or gynecology/women's health.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Vikrant Sahasrabuddhe, M.B.B.S., M.P.H., Dr.P.H.
Telephone: 240-276-7332
Fax: 240-276-7828
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall (use for 'Overall' component)	12 pages
Admin Core (use for 'Administrative and Coordinating Core')	6 pages
Program (use for 'Clinical Trials Program')	12 pages
Core (use for 'Data Management and Statistical Core' and 'Central Laboratory Core')	6 pages each

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: one (required);
• Administrative and Coordinating Core: one (required);
• Clinical Trials Program: one (required);
• Data Management and Statistical Core: one (required); and
• Central Laboratory Core: one (required)

When preparing your application in ASSIST, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form. The title of the application should incorporate the name(s) of the partnering LAC country(-ies).

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Facilities and Other Resources:

In addition to standard elements, provide documentation for the following aspects reflecting the unique capabilities and attributes of the multinational scientific environment of the proposed Partnership Centers:

• Access and linkages to facilities with appropriate pool of potential participants for the proposed clinical trials, e.g., antiretroviral therapy clinics for HIV-infected individuals, HIV testing and counseling centers, access to clinics and hospitals providing management for individuals detected with cancer.
• Site infrastructures for conducting clinical trials within or geographically proximal clinical care sites, including access to appropriate manpower and facilities for dealing with unique issues (e.g., challenges around stigma during care seeking, multi-specialty care coordination, biosafety measures) that have a bearing on conducting research among HIV-infected individuals,
• Information technology infrastructure (e.g., computing capacity, access to specialized software, broadband internet connectivity, etc.) that may be critical for conducting the proposed clinical trials at each of the partnering institutions.
• Laboratory infrastructure (e.g., physical space attributes, biorepository and specimen management systems, etc.) critical for supporting the conduct of the clinical trials at each of the partnering institutions.

Other Attachments:

Applicants must provide documentation specified below (uploaded as a separate PDF), using the indicated filename (which will serve as application bookmark).

Attachment 1: Summary tables of past clinical trials. Use filename "Previous Clinical Trials".

Provide a summary table of accrual accomplished by the applicant team to clinical trials and research studies sponsored by NIH and other funding organizations during the past 5 years. In addition, include older contributions to clinical trials (up to past 8 years), but only if they are particularly relevant to the to the scope of RFA-CA-18-018.

Attachment 2: Documentation of ability to recruit study participants. Use filename "Potential Participants".

Provide a summary of the potential facilities and resources (e.g., antiretroviral therapy clinics, HIV testing and counseling centers, other health care clinics/facilities) available in the implementation catchment area(s) to recruit potential participants for clinical trials proposed though this Funding Opportunity Announcement.

Enter primary site only. Only the U.S. applicant institution site should be referenced here.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Outline the overall goal of the Partnership Center, identifying the selected focus area(s) and the overarching research questions to be addressed by the three anticipated clinical trials.

Research Strategy: Present the Overall Research Strategy in the sub-sections A-D defined below.

Subsection A: Partnership Center Overview

In this sub-section, address, at a minimum, the following aspects:

• Describe the overall vision for the Partnership Center and explain the significance of the chosen research theme(s) as well as directions intended for the three anticipated clinical trials.
• Outline how the proposed research directions to be addressed by clinical trials aligns with country-specific/LAC region-specific clinical and public health priorities/gaps and how they address the NIH criteria for high or medium priority HIV/AIDS research.
• Provide details on how the Partnership Center may contribute to research on HPV-related cancers in HIV-infected individuals. In particular, address the potential to improve and optimize prevention clinical interventions for these cancers in the target country(-ies) in the LAC region specifically, and LMICs in general.
• Explain specifically how the results of the proposed clinical trials may spur next steps towards either further large-scale evaluation the proposed intervention (drug, vaccine, device, etc.) or implementation of the strategy, with a goal to eventually prevent the HPV-related cancers in HIV-infected individuals in the participating country(-ies) in specific, and LMICs in general.

Sub-section B: Collaborative Experiences

In this sub-section, without repeating information provided in Biosketches, address the following aspects:

• Briefly describe the collective strengths of the team related to collaborative, multi-institutional clinical research in the fields directly relevant to this FOA (HIV/AIDS, HPV, cancer) as well as other clinical areas, as applicable (e.g., infectious diseases, reproductive health, gynecology, etc.).
• Provide highlights demonstrating the productivity of past/ongoing collaborative partnerships, in terms of substantially increased in-country clinical care delivery or clinical trials/clinical/public health research capabilities.
• As applicable, indicate how collaborations among partners involved have benefited the LAC institution and LAC country(-ies)/LAC region.
• Summarize any other relevant contributions of the team to collaborative, multi-institutional clinical research

Sub-Section C: Organizational Structure of the Partnership Center.

In this sub-section, describe the Organizational Structure of the Partnership Center, including the organizational chart, chain of command, and individual responsibilities for the key personnel.

• Explain clearly how the proposed Partnership Center is expected to realize the required equal and sharing nature of the proposed partnership (e.g., reflected by a balanced distribution of responsibilities and leadership of research projects and cores).
• Outline the roles and responsibilities of the U.S. and LAC region investigators in accomplishing the proposed research aims, and in managing the collaboration of the Partnership Center.

Sub-section D: Overall Strategy for Scientific Integration and Impact.

In this sub-section, outline how the Clinical Trials Program and the supporting Cores will integrate scientifically. Specifically, address the following:

• Explain the potential to increase clinical research capacity in the proposed LAC region country(-ies) and enhance/facilitate the professional development of scientific leadership in the partnering LAC region institution(s).
• Include any information about available unique clinical and research-related resources (e.g., previous NIH-/other agency-funded infrastructure for clinical trials, ongoing/previous collaborative activities between the proposed partnering entities, etc.) that may be relevant for the proposed collaborative studies.
• Explain how the available recruitment and retention resources and strategies (e.g., access to populations for enrollment in clinical trials, access to clinical databases for linkages for prior medical history, technology-based strategies/programs for participant retention, etc.) may enhance research experiences within the partnering institutions and/or collaborations across other centers/consortia.
• As applicable, mention any additional resources, programs, and partnerships that Partnership Center may plan to collaborate with or may benefit from having access to. Consider, for example, other NIH/NCI programs such as NCI's AIDS Malignancy Consortium, NIAID HIV/AIDS Clinical Trials Networks, NCI Division of Cancer Prevention's Early Phase Cancer Prevention Clinical Trials Consortia Program, NCI Center for Global Health's Cancer Detection, Diagnosis, Treatment Technologies for Global Health program, NIH Fogarty International Center's HIV Research Training Programs for Low-and Middle-Income Country Institutions as well as non-NIH programs that may provide synergies and opportunities for scientific interactions, harmonization of protocols for evaluation of specific technologies/approaches, and partnerships for training and/or career development for investigators, among other benefits.

Letters of Support:

Letters of support that describe commitments and availability of resources to Partnership Center must be provided by the institutional leadership from each partnering institution. All letters of support for the entire application should be included here. Applications failing to provide such letters shall be deemed incomplete and will not be reviewed.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Resource Sharing Plan should be provided only under the 'Overall' component. It should cover all the activities proposed for the entire Partnership Center application.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Additional guidance: do not enter any Study Record under the Overall component (all Study records must be entered under "Research Program" component.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Additional guidance: do not enter any Delayed Onset Study under the Overall component (all Delayed Onset Studies must be entered under "Research Program" component.

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? (Answer: No) and 'Is the Project Exempt from Federal regulations? (Answer: No) questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question (Answer: No).

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Administrative and Coordinating Core must be co-led by the Project Director/Principal Investigator of the U.S. applicant institution and the collaborating Project Director/Principal Investigator at the LAC region partnering institution(s).

Budget forms appropriate for the specific component will be included in the application package.

Include budgets for the following items in the Administrative Core budget.

• PDs/PIs Effort. Each of the two Partnership Center PDs/PIs (from both the U.S. and the LAC region) will be expected to have a significant effort commitment (at least 2.4 person-months required).
• Salary support for faculty and research staff from the LAC region institution(s) must follow salary guidelines of the institution(s).
• Travel costs: Travel by PD(s)/PI(s) to the collaborating institution(s), monitoring and auditing visits, Annual Program Meeting travel, travel to scientific meetings or research training workshops, and any additional travel relevant to the goals of the Partnership Center should not exceed $75,000 direct costs annually. Each application is required to budget for supporting travel to an annual program meeting of the U54 Partnership Centers program. It is anticipated that every meeting will be attended by the PD(s)/PI(s), Core Director(s), Clinical Trial Chairperson(s), and selected study investigators and staff (up to ten total). Applicants must plan that at least one of the Partnership Center Meetings during the project period will be held in the United States.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Provide the overall broad goals for providing administrative management and coordination across the Partnership Center in support of achieving the proposed clinical goals.

Research Strategy: Use sub-sections A-B defined below to describe the following elements:

Sub-Section A: Leadership and Facilitation Structure:

Address the following aspects:

• Describe the leadership structure (provide a diagram) and explain its key governance policies, the chain of responsibility for decision making, conflict resolution, etc.
• Articulate the process for communicating with members of the Partnership Center, decision making, and conflict resolution. Outline contingency plans to remedy setbacks, delays, logistics issues, ethical/regulatory approvals, travel/visa issues, and other possible hurdles that may be encountered in developing a Partnership Center.
• Explain how the Administrative and Coordinating Core will provide the necessary infrastructure and support services for facilitating the smooth conduct of the clinical trials and all related activities.
• If applicable, describe ongoing efforts to enhance and support research administration at the LAC region institution and how this effort may help fill previously identified gaps at the institutional level.
• Explain how the proposed Partnership Center may interact with other NIH- and NCI-supported programs/resources, e.g., in terms of facilitation for staff training, protocol harmonization, regulatory coordination, and/or career-enhancing opportunities for Partnership Center investigators.

Sub-Section B: External Scientific Advisory Group:

Applicants must propose to convene an External Scientific Advisory Group (ESAG) to advise the Partnership Center leadership on scientific directions and priorities for clinical trials.

• Suggested membership of the ESAG should include at least three to five representatives from among (but is not limited to) senior clinicians, health policy makers, institutional and government leaders, key opinion leaders, community advocates from the proposed LAC region country(-ies). The ESAG should have a balanced representation of U.S. and LAC region members. Describe required expertise and profiles of potential members but do not provide any names and do not contact such individuals prior to application review.
• Describe how the ESAG will play a role of serving as a virtual bridge between the Partnership Center and the catchment area communities to help facilitate and enhanced the enrollment and conduct of clinical trial protocols via broader community involvement, as well as help translate eventual research outcomes into clinical and public health policy changes.

In this section, provide details on the process the Administrative and Coordinating Core will follow in identifying potential members and convening the ESAG. Do not mention any specific names for the ESAG in the application; rather only indicate the desirable expertise/profiles of potential members for the ESAG.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix:

Limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative and Coordinating Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Program.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

One clinical trial should be described in substantive details and should have a 'Delayed Start' study record while two clinical trials should be presented as concepts and should have 'Delayed Onset' study records.

SF424 (R&R) Cover (Clinical Trials Program)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title: "Clinical Trials Program"
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Clinical Trials Program)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Trials Program)

Human Subjects: Answer only the Are Human Subjects Involved? (Answer: Yes) and 'Is the Project Exempt from Federal regulations? (Answer: No) questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project/Performance Site Location(s) (Clinical Trials Program)

List all performance sites that apply to the Clinical Trials being proposed.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Clinical Trials Program)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Clinical Trials Program Chairperson' and provide a valid eRA Commons ID in the Credential field.
• The Clinical Trials Program Chairperson should be the contact PD/PI of the Partnership Center.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• The list of Senior/Key persons should include individuals designated as Clinical Trial Protocol Chairpersons and co-Chairpersons (if already identified). Each Clinical Trial Protocol Team should be led by U.S. and LAC Protocol Co-Chairperson(s). These Co-Chairperson(s) may or may not be identified at the time of application and may be added/changed during the course of the project period, contingent on approval by the NCI. Include research scientists and clinicians of appropriate profile from the applicant institution and collaborating institutions in the U.S. and LAC region in each Protocol team.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Clinical Trials Program)

Budget forms appropriate for the specific component will be included in the application package.

• Budget request for Clinical Trials Program (which should cover activities related to the development and conduct of three individual clinical trials) must be at least two-thirds of the total direct costs requested for the Partnership Center.
• The allocation of the budget for each clinical trial (total and for each year) should be proportional to the expected activities during the appropriate phases (preparatory, launch, and conduct) of each trial.
• A minimum level of effort of 1.2 person-months (10% effort) for each Protocol Co-Chairperson is recommended.
• Salary support for faculty and research staff from the LAC institution(s) must follow salary guidelines of the institution(s).
• Budget Justifications: Describe the specific functions of all key personnel, consultants, collaborators and support staff. For all years, explain and strongly justify any unusual items requested (e.g., major equipment).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Clinical Trials Program)

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions.

Specific Aims:

Outline three specific aims for the Clinical Trials Program, which should include one specific aim per anticipated clinical trial. Each Specific Aim should be focused on the overarching prevention science area (immunoprevention/vaccines, screening and triage, and precancer treatment; specified in Section I 'Objectives, Scope and Requirements') sought to be addressed by each anticipated clinical trial. As applicable, provide the underlying hypotheses and the relevant primary and secondary/ancillary endpoints for each specific aim.

Research Strategy:

The Research Strategy section should broadly describe the Significance, Innovation, and Approach for each of the Clinical Trial. For the concept of the proposed fully developed Clinical Trial 1 (anticipated to be started within the first year of the project period), the sub-section on Approach should have adequate details of the study design and protocol implementation, whereas for the two developmental concepts for Clinical Trials 2 and 3 (anticipated to start later in the project period), detailed information and considerations may not be known at the time of application. All clinical trial concepts must be conceptually sound, supported by compelling underlying biological rationale and preclinical data, efficiently and effectively enroll human research subjects, feasible to be conducted and completed within available resources and timelines, and should be well integrated with the general current state of the field and relevance of clinical and public health needs in the communities in which it is being implemented in the LAC region.

Sub-Section A: Significance.

• Identify which of the Central Research Areas (specified in Section I 'Objectives, Scope and Requirements') is being addressed by each Clinical Trial.
• Explain clearly in relevant sub-sections how each anticipated protocol conforms to the general requirements outlined in Section I 'Objectives, Scope and Requirements', including the NIH criteria for high priority research on HIV/AIDS defined in NOT-OD-15-137.
• Describe the central problem/hypothesis to address, underlying biologic rationale and relevant preliminary/preclinical data, and describe how each anticipated clinical trial will contribute to meeting the goals and objectives of the program and the specific central research theme.
• Indicate the Program's relevance to the specific situation of the partnering LAC region country(-ies) and how it is expected to leverage and strengthen existing research capacity at the LAC region institution(s). Explain the importance of the problem(s) or critical barrier to progress that the proposed Program addresses.
• Explain how the proposed project will improve scientific knowledge, technical capability, and/or clinical practice in one or more broad fields.

Sub-Section B: Innovation.

• Describe how the results of the clinical trials may provide a novel or innovative approach that could have the potential to improve the preventive clinical care management of HPV-related cancers in the partnering LAC region country(-ies) and improve the health outcomes of patients with HIV.
• If applicable, explain how the application challenges and seeks to shift current research or clinical practice paradigms.
• Highlight any novel and/or refined/improved theoretical concepts, approaches or methodologies, instrumentation or interventions to be developed or used, and any advantage over existing methodologies, instrumentation, or interventions.

Sub-Section C: Approach.

• Describe the broad clinical trial implementation plan, including the overall strategy and approaches proposed for Protocol Teams to collaboratively develop and finalize study design, facilitate study conduct, monitor the study, conduct data analysis, report results and prepare scientific publications.
• Describe the feasibility considerations such as availability of potential pool of participants for accrual and retention, and plans for mitigating any challenges and limitations.
• Discuss potential problems, alternative strategies, and benchmarks for success anticipated to achieve the aims.
• For interventions in their early stages of clinical development, describe any strategy to establish feasibility, and address the management of any high-risk aspects of the proposed work.
• For laboratory investigations and data analyses that are not feasible at the LAC region site, explain the reasons and, if appropriate, provide the timeline for the transfer to the LAC region site of the requisite expertise/skills/technology etc.

Preparatory work for the trials (e.g., enrollment strategies, refinement of data collection instruments, staff training) can be proposed as part of the project activities ahead of the actual launch.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Clinical Trials Program)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Additional Guidance:

Complete Study Record only for the proposed fully developed Clinical Trial 1 (anticipated to be started within the first year of the project period).

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Complete Delayed Onset Study for the Exploratory/Developmental Concepts for Clinical Trial 2 and Clinical Trial 3.

Justification Attachment: Indicate that the Delayed Onset Study (Clinical Trial #2 and Clinical Trials #3) will be designed and conducted by the Partnership Center during the Project Period. Each clinical trial protocol will be subject to review and approval by the NCI prior to activation through the Partnership Center.

When preparing your application in ASSIST, use Component Type Core

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Data Management and Statistical Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title (i.e. "Data Management and Statistical Core").
• Proposed Core Start/Ending Dates

PHS 398 Cover Page Supplement (Data Management and Statistical Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management and Statistical Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions. Answer 'No' to both these questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Data Management and Statistical Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Data Management and Statistical Core)

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of 'Core Director' and provide a valid eRA Commons ID in the Credential field. The Data Management and Statistical Core may be, but does not have to be, co-led by US and LAC investigators.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Data Management and Statistical Core)

Budget forms appropriate for the specific component will be included in the application package.

Salary support for faculty and research staff from the LAC institution(s) must follow salary guidelines of the institution(s).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Management and Statistical Core)

Specific Aims: Provide the specific aims for the Data Management and Statistical Core outlining support for the three clinical trials it will serve.

Research Strategy: Describe how the Data Management and Statistical Core will function with both virtual or physical infrastructures to provide support to the proposed Clinical Trials Program. Describe the intended function and rationale for the proposed Data Management and Statistical Core. The description must contain the following information:

• Explanation how the proposed Core matches the research needs of Partnership Centers by providing services and technical consultations such as those for the following:
• management and handling of key clinical and research data;
• statistical considerations during the entire continuum of study conduct (design, implementation, analysis, reporting).
• The key characteristics of the proposed Core (including approaches to ensure rigor and proper quality control) and anticipated benefits for the projects to be served.
• The justification for the location of the proposed Core.
• If similar resources are already available at the LAC institution, how will these resources be enhanced through this Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Data Management and Statistical Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Given that applicants are not proposing specific clinical trials as part of this Core, Study Record should NOT be completed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Core

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Central Laboratory Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title (i.e. Central Laboratory Core).
• Proposed Core Start/Ending Dates

PHS 398 Cover Page Supplement (Central Laboratory Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Central Laboratory Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions. Answer 'No' to both these questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Central Laboratory Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Central Laboratory Core)

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of 'Core Director' and provide a valid eRA Commons ID in the Credential field. The Central Laboratory Core may be, but does not have to be, co-led by U.S. and LAC region investigators.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Central Laboratory Core)

Budget forms appropriate for the specific component will be included in the application package.

Salary support for faculty and research staff from the LAC institution(s) must follow salary guidelines of the institution(s).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Central Laboratory Core)

Specific Aims: Provide the specific aims for the Central Laboratory Core outlining support for the three clinical trials it will be expected to serve.

Research Strategy:

Describe how the Central Laboratory Core will function with both virtual or physical infrastructures to provide support to the three proposed clinical trials. Describe the intended function and rationale for the proposed Central Laboratory Core. The description must contain the following information:

• Explanation how the proposed Core matches the research needs of Partnership Center by providing expert services and technical consultations such as those for:
• Central pathology endpoint reviews and quality assurance for virologic/immunologic testing for biological specimens
• Optimizing sample collection, handling, shipment/transfer, and short- and long-term storage and retrieval.
• The key characteristics of the proposed Core (including approaches to ensure rigor and proper quality control) and anticipated benefits for the projects to be served
• The justification for the location of the proposed Core.
• If similar resources are already available at the LAC institution, how will these resources be enhanced through this Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Central Laboratory Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Given that applicants are not proposing specific clinical trials as part of this Core, Study Record should NOT be completed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(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 NIH.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI, NIH. Applications that are incomplete, non-compliant, and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and interventions that are not by themselves innovative but may address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

For this FOA, note the following:

Reviewers will provide an overall impact score for the entire Partnership Center application. In addition, assigned reviewers will provide individual "criterion scores" for the Overall criteria but not for the other components.

All other components of the Center (i.e., Administrative and Coordinating Core, Clinical Trials, Data Management and Statistical Core, and Central Laboratory Core) will be evaluated but each will receive only one overall adjectival (not numerical) rating.

For the evaluation of the Partnership Center application, the Clinical Trials will be emphasized as the research base of each Center, with additional components enhancing and integrating the Center.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Partnership Center 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 Clinical Trials proposed).

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 Clinical Trial that by its nature is not innovative may be essential to advance a field.

Does the Partnership Center address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the Partnership Center 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 scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this FOA:

Do the clinical trials proposed through the Partnership Center contribute to research on HPV-related cancers in HIV-infected individuals and have the potential to improve and optimize prevention clinical interventions for these cancers in the target country(-ies) in the LAC region specifically, and LMICs in general?

Will results of the proposed clinical trials spur next steps towards either further large-scale evaluation the proposed intervention (drug, vaccine, device, etc.) or implementation of the strategy, with a goal to eventually prevent the HPV-related cancers in HIV-infected individuals in the participating country(-ies) in specific, and LMICs in general?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Partnership Center? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, 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?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this FOA:

Does the team of investigators have strengths in conducting collaborative, multi-institutional clinical research in HIV/AIDS, HPV, cancer or clinical areas related to this FOA (e.g., infectious diseases, reproductive health, gynecology, etc.) Have past/ongoing collaborative partnerships resulted in substantially increased in-country clinical care delivery or clinical trials/clinical/public health research capabilities and benefited the LAC institution and LAC country(-ies)/LAC region?

Does the proposed Partnership Center reflect a balanced distribution of responsibilities and leadership of research projects and cores necessary to realize the equal and sharing nature of the proposed partnership? Have roles and responsibilities of the U.S. and LAC investigators in accomplishing the proposed research aims, and in managing the collaboration of the Partnership Center clearly delineated?

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Partnership Center? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Partnership Center involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed? Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this FOA:

Are plans for the proposed Partnership Center designed to increase clinical research capacity in the proposed LAC country(-ies) and enhance/facilitate the professional development of scientific leadership in the partnering LAC institution(s)? Are plans for enhancing research experiences within the partnering institutions and/or collaborations across other centers/consortia via utilization of unique resources and strategies for recruitment and retention well described? Are plans for collaboration with other NIH/NCI and/or non-NIH programs that may provide synergies and opportunities for scientific interactions, protocol harmonization, or training/career development for investigators well described?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

As applicable for the Partnership Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed Partnership Center involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not applicable.

Not applicable.

Not applicable.

As applicable for the Partnership Center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not applicable.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Reviewers will provide only one overall adjectival impact rating for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

• Is the management proposed appropriate for scientific administration as well as fiscal administration, procurement, and personnel management? Are leadership structures, governance policies, and the chain of responsibility for decision making and conflict resolution well described? Are contingency plans to remedy and mitigate setbacks and delays articulated?
• If appropriate, how well do the proposed activities for strengthening research administration for the proposed clinical trials address the needs of the LAC region institution? Do these activities provide the necessary infrastructure and support services for facilitating the smooth conduct of clinical trials and all related activities?
• What is the likelihood that the proposed coordinating activities provide opportunities for career enhancement activities to meaningfully aid junior investigators on their way towards research leadership? To what degree will these activities facilitate building capacity and help fill previously identified gaps at the institutional level in conducting HIV/AIDS and cancer research at the partnering institutions?
• Are plans for interaction with other NIH and NCI-supported programs/resources, e.g., in terms of facilitation for staff training, protocol harmonization, regulatory coordination, and/or career enhancing opportunities for Partnership Center investigators well described?

Reviewers will consider each of the review criteria outlined below to assess the scientific merit of the Clinical Trials being proposed but will give only one adjectival rating for the Clinical Trials Program (criterion scoring is not used for this component).

• Does the proposed Clinical Trials Program address important scientific questions related to evaluating the safety, efficacy, or effectiveness of interventions focused on prevention for HPV-related cancers among HIV-infected individuals?
• Is the scientific rationale to test the proposed hypotheses or interventions well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms?
• If the aims of the clinical trial protocols are achieved, how will scientific knowledge and clinical practice be improved? How will successful completion of the clinical trials be catalytic in changing clinical practice and health care policy for preventative interventions in LMICs in general and the LAC region in specific? For trials focusing on an intermediate endpoint (mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints), are they needed to advance scientific understanding?
• Are the Clinical Trial Protocol Chairperson(s) and study team members well suited to lead and collaboratively conduct the proposed trials? Will the investigators utilize complementary and integrated expertise and are their leadership approach, governance and organizational structure appropriate for the conduct of the clinical trials?
• Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the clinical trials? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?
• Are potential problems, alternative strategies, and benchmarks for success presented? If the trial(s) seek to evaluate relatively earlier stages of the clinical development pipeline, will the strategies establish feasibility, and will particularly risky aspects be managed?
• Are there adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety?

Reviewers will provide only one overall adjectival impact rating for this Core (criterion scoring is not used for this component). Reviewers will consider the following aspects in the determination of the merit of the Data Management and Statistical Core:

• Are the proposed Core capabilities and functions responsive to the specific research needs of the Clinical Trials being proposed in the Partnership Center?
• Are the Core Director(s) and Key personnel involved in the Data Management and Statistical Core capable of providing latest best practices and physical and virtual infrastructures for the management and handling of key clinical and research data?
• Are plans for providing technical assistance for statistical considerations during the entire continuum of study conduct (design, implementation, analysis, reporting) articulated with appropriate details?

Reviewers will provide only one overall adjectival impact rating for this Core (criterion scoring is not used for this component). Reviewers will consider the following aspects in the determination of the merit of the Central Laboratory Core:

• Are the proposed Core capabilities and functions responsive to the specific research needs of the Clinical Trials being proposed in the Partnership Center?
• Are the Core Director(s) and Key personnel involved in the Central Laboratory Core capable of utilizing best practices for central endpoint reviews and quality assurance for virologic/immunologic testing on biological specimens to be collected and analyzed in the proposed clinical trials?
• Are plans for providing consultations for optimizing the processes of sample collection, handling, shipment/transfer, and short- and long-term storage and retrieval articulated with appropriate details?

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by National Cancer Institute in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities. Programmatic priorities to consider may include, for example, geographic distribution of the project performance sites across the LAC region, relevance to other NIH/NCI-funded research activities, etc.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the following primary responsibilities for:

• Defining objectives and approaches of the Partnership Center and providing leadership and coordination across clinical trial protocol teams, Core Directors, and collaborating investigators.
• Ensuring scientific integrity, productivity, governance, and fiscal accountability for the Partnership Center.
• Overseeing the Administrative and Coordinating Core and providing overall administration, coordination, communication, and management including, but not limited to, the following activities: training and study monitoring, regulatory support, submission to institutional review boards (IRBs) and institutional oversight committees, recruitment and retention efforts, convening and liaison with data safety and monitoring boards, ensuring certification of all key personnel in training on the Protection of Human Subjects and Good Clinical Practices (GCP).
• Overseeing protocol amendments/status changes, quality assurance efforts, and study monitoring.
• Coordinating efforts with the Data Management and Statistical Core Director(s) for efficient data management and statistical design and analytical aspects of each of the proposed Clinical Trials.
• Coordinating efforts with the Central Laboratory Core Director(s) for efficiently managing and coordinating acquisition and shipping of protocol-specified biological specimens (with relevant clinical data) to appropriate laboratories for testing and tumor/specimen repository for storage of specimens for future correlative laboratory studies.
• Ensuring adherence to requirements regarding investigational drug management and federally mandated regulations and protocol and performance reporting, submission of annual progress reports to the NCI that describe activities and accomplishments during the previous year of funding, and submission of timely reports of all serious and/or unexpected adverse events to the NCI and relevant regulatory agencies.
• Partnering with Co-Chairpersons of each Clinical Trial Protocols to oversee protocol development, including study design, definition of objectives and approaches, planning, implementation, analysis, and publication of results, interpretations, and conclusions.
• Ensuring accurate and timely knowledge of the progress of each study by developing standard procedures for timely data collection and data management consistent with the more intensive data requirements and the need for rapid reporting necessary for pilot, Phase I, and Phase II prevention clinical studies.
• Ensuring protection of confidentiality of research participants at all steps in the submission and analysis of clinical trials data and ensuring the technical integrity and security of the data management systems,
• Providing NCI in a timely manner, upon the request of the NCI Project Scientist, true copies of data files and supporting documentation for all NCI-supported protocols, as well as providing to the NCI periodic study reports to include information detailing patient accrual and demographics, data timeliness, toxicity experienced by study participants, and other items including outcome data as appropriate.
• Establishing routine electronic communication with Clinical Trials site institutions to facilitate study monitoring, and to facilitate the work of the Protocol teams. Relevant communication methods include e-mail, teleconferences, video conferences, and web site postings.
• Providing mentorship and networking opportunities for new/early stage/junior investigators as well as patient advocates in clinical trials research/activities.
• Adhering to and complying with the decisions and recommendations of the NCI Clinical Trials Oversight Committee and Partnership Center Coordinating Committee to the extent consistent with applicable grant regulations.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

Designated NCI Program Director(s) will have substantial involvement as Project Scientist(s). Additionally, an NCI Program Director, acting as Program Official will be responsible for the normal,

scientific and programmatic stewardship of the award and will be named in the award notice.

Activities of substantially involved NCI staff members will include:

• Ensuring that clinical trials proposed are within the research scope of the Partnership Center Program and relevant to the state-of-the-science, NIH/NCI priorities, resources, and availability of funding.
• Finalizing reviews of clinical trial protocols and amendments after evaluation by the NCI Clinical Trials Oversight Committee and monitoring the progress and performance of the Partnership Centers.
• Serving as a resource for scientific information on trial/study design and as scientific liaison for scientific opportunities resulting from NIH/NCI-supported research programs for facilitating appropriate collaborations.
• Evaluating and approving of clinical trial collaborations with outside organizations including review of any agreements/memoranda of understanding (MOUs) for compliance with NIH/NCI and Federal policies.
• Overseeing data management and monitoring programs for the proposed clinical trials as well as overseeing and participating as necessary in on-site auditing programs and quality assurance programs.
• Overseeing data and safety monitoring plans for the proposed Clinical Trials, and final review and approval of requests for use of any bio-specimens collected per the approved protocol for Clinical Trials.
• Ensuring compliance with the United States Food and Drug Administration (FDA) for any relevant investigational agents and ensuring compliance with OHRP and other federal regulations for research involving human research subjects including compliance with Good Clinical Practice (GCP) guidelines: http://www.fda.gov/oc/gcp/default.htm and https://ctep.cancer.gov/branches/ctmb/clinicalTrials/docs/good_clinical_practices.pdf.
• Reviewing data collected and/or generated under this Cooperative Agreement.

NCI Clinical Trials Oversight Committee: The NCI Project Scientist(s) will organize an NCI Clinical Trials Oversight Committee, which will be composed of representatives from relevant NCI Divisions, Offices, and Centers with appropriate expertise. This Committee will be responsible for final concurrence regarding concept approval and initiation of individual clinical trials.

In addition, the Committee will provide recommendations to the NCI Project Scientist(s) and Coordinating Committee regarding oversight for the conduct of these trials, coordination of Partnership clinical trials with other relevant NCI-funded initiatives, and other strategic aspects of the Partnership Centers Program.

The NCI Clinical Trials Oversight Committee may recommend suspension, termination, or curtailing an ongoing clinical trial in the event of unexpected/serious adverse events, substantial shortfall in participant accrual, data reporting, inadequate quality control in data collection, suboptimal clinical care of study participants, non-adherence to biohazard precautions, and other serious medical and/or regulatory issues. The Committee may also recommend other corrective actions in case of sub-optimal performance of the awardees and/or their affiliated institutions (including recommendation to restructure sub-contractual arrangements).

The NCI reserves the right to reduce the budget or withhold an award in the event of substantial awardee underperformance or other substantial failure to comply with the terms of award.

Areas of Joint Responsibility include:

General aspects of collaboration on study development and conduct especially with respect to compliance with federal regulations for clinical trial research, conduct of Data and Safety Monitoring Boards (DSMBs) for relevant phase 3 trials and randomized phase 2 trials.

Partnership Center Coordinating Committee: This committee will be responsible for coordinating and harmonizing scientific activities between the funded Partnership Centers. The Committee will be composed of the following voting members:

• Two representatives from each U54 Partnership Center (the PD(s)/PI(s) or a PD/PI and a designated senior investigator) who will have one vote each; and
• NCI Project Scientist(s), who will have collectively one vote.

The Coordinating Committee will be chaired on a rotating basis once per year by each of the two Partnership Center PDs/PIs.

The Coordinating Committee will meet at least quarterly via teleconference or videoconference to share information on planning, study progress and challenges, preliminary results and analyses in progress.

The Coordinating Committee may establish working groups/sub-committees as needed, e.g., to address scientific and administrative issues and/or to coordinate policies, harmonize protocols, implement best practices for clinical trials conduct across sites and participating countries, coordinate regulatory approvals, etc. This decision will be made by the existing voting members of the Coordinating Committee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Coordinating Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Vikrant Sahasrabuddhe, M.B.B.S., M.P.H., Dr.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7332
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.