Department of Health and Human Services
Part 1. Overview Information

 

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title

Limited Competition: AIDS Malignancy Consortium (AMC) (UM1 Clinical Trial Required)

Activity Code

UM1 Research Project with Complex Structure Cooperative Agreement

Announcement Type

Reissue of RFA-CA-14-502

Related Notices

NOT-OD-19-128, Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research.

NOT-OD-19-137, Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research.

Funding Opportunity Announcement (FOA) Number

RFA-CA-19-056

Companion Funding Opportunity

None

Number of Applications

Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.393, 93.394, 93.395, 93.396

Funding Opportunity Purpose

The purpose of the proposed Funding Opportunity Announcement (FOA) is to enable the provision of support for AIDS Malignancy Consortium (AMC).

AMC is a major infrastructure intended to stimulate cooperative research efforts in the following areas:

Design, development, and evaluation of clinical interventions for the prevention and treatment of HIV-associated malignancies;

Development of more effective therapeutics and management strategies for HIV-associated malignancies;

Investigation of the biology of HIV malignancies within the context of clinical trials;

Management of issues of international importance in HIV associated-malignancies; and

Distribution of excess tumor tissue and other relevant biologic fluids to the AIDS and Cancer Specimen Resource for ongoing or future investigations.

The AMC must consist of the following functional units: a Coordination Center; Clinical Trial Sites; Network Laboratories; and a Statistical Center. The AMC team must have scientific disease-oriented Working Groups to study Kaposi Sarcoma, Lymphoma, Human papilloma virus-associated cancers, and non-AIDS-Defining cancers. The Network Laboratories will be responsible for routine clinical trial support activities, pathogenesis-driven correlative studies, and clinical pharmacology and pharmacokinetics studies of anticancer/antiviral interactions. All clinical trials to be conducted by the AMC must be available to subjects of all racial/ethnic groups.

Key Dates

 

Posted Date

September 11, 2019

Open Date (Earliest Submission Date)

December 10, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

Only accepting applications for the AIDS Application Due Date(s) listed below.

AIDS Application Due Date(s)

January 10, 2020, by 5:00 PM local time of applicant organization.

All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on the listed date(s).

No late applications will be accepted for this Funding opportunity Announcement.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Scientific Merit Review
Advisory Council Review

May 2020

Earliest Start Date

September 2020

Expiration Date

January 11, 2020  

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) 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.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

    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


    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    The purpose of the proposed Funding Opportunity Announcement (FOA) is to enable the provision of support to the AIDS Malignancy Consortium (AMC) to conduct research activities in the following areas:

    • Maintaining a multidisciplinary research team that will develop and implement the scientific research agenda of the consortium;
    • Conducting pilot phase, Phase I, Phase II, and Phase III clinical trials of novel agents and/or innovative approaches of AIDS-related cancer management;
    • Developing and conducting domestic and international clinical trials in the treatment and/or prevention of AIDS-related cancers and non-AIDS defining cancers (NADC) associated with HIV disease;
    • Developing correlative studies in the context of the clinical trials; and
    • Distribution of excess tumor tissue and other relevant biologic fluids to the AIDS and Cancer Specimen Resource for ongoing or future investigations.

    To be considered for the renewal award, the Consortium must have disease oriented working groups that will address AIDS-defining and non-AIDS-defining cancers occurring among people living with HIV, such as Kaposi sarcoma, lymphoma, cervical cancer, anal cancer, liver cancer, lung cancer among others.

    The proposed AMC must consist of the following functional units:

    • An Operation Center;
    • Clinical Trial Sites (CTS, domestic and international);
    • Network Laboratories; and
    • A Statistical Center.

    The Network Laboratories will be responsible for routine clinical trial support activities, pathogenesis-driven correlative studies, and clinical pharmacology and pharmacokinetics studies of anticancer/antiviral interactions. All trials conducted by the AMC will be available to subjects of all racial/ethnic groups.

    The AMC is expected to continue the conduct of the "ANCHOR" study, which AMC initiated in the current funding period. The ANCHOR [i.e., Anal Cancer High Grade Squamous Intraepithelial Lesion (HSIL) Outcomes Research] study, with a sample size of 5058 patients, is designed to determine whether treatment of anal HSIL prevents anal cancer. This study is needed before widespread screening for anal HSIL can be adopted.

    The Consortium will be expected to collaborate with NIH-supported HIV/AIDS Clinical Trials Networks and other NCI-supported cooperative groups and international networks (such as the NCI’s National Clinical Trials Network) to achieve the goals of the AMC and to leverage NCI funds in areas of mutual research interests.

    Background:

    Cancer has been a major feature of the HIV epidemic since its beginning. Three of these cancers, Kaposi sarcoma (KS), high-grade B cell non-Hodgkin lymphoma (NHL), and invasive cervical cancer, are called AIDS-defining cancers (ADC) when they develop in HIV-infected individuals.  HIV-infection is also associated with increased risk of a number of other cancers. The spectrum of cancers seen in HIV-infected individuals is complex and is changing as the epidemic evolves.

    With the introduction of combination antiretroviral therapy (cART) for treatment of HIV infection in the United States and other developed countries, the incidence of certain AIDS-defining malignancies decreased. However, the incidence of AIDS-defining cancers has more recently stabilized, and these cancers continue to be a major cause of morbidity and mortality.  In Africa and other regions of the developing world where access to cART is more limited, AIDS-defining cancers continue to be among the most common tumors overall.  More than two-thirds of the HIV-infected population live in Sub-Saharan Africa, and this region is also an epicenter of KS and other virally-related malignancies such as cervical cancer and Burkitt lymphoma. In this region, AIDS-defining malignancies (KS, aggressive NHL and invasive cervical cancer) are among the most common tumors overall.

    In regions in which anti-retroviral therapy is more widely used, HIV-infected patients are living longer, and the population of HIV-infected patients is aging. In part, as a result of this, while the rates of ADC are decreasing the rates of certain non-AIDS-defining cancers (NADCs) are on the rise, with significant increases in anal cancer, lung cancer, liver cancer, oropharyngeal cancer and several other tumors. Various other cancers, such as breast or prostate cancer that affect the general population are not more common in the HIV-infected population. Nonetheless, these cancers do contribute to the complexity of cancer patterns in the HIV-infected population.  All these cancer patterns lead to complex challenges for the clinical community regarding development of standards of care and appropriate treatment regimens. Some recent studies have shown that in areas where cART is widely available, cancer is now the most common cause of death in HIV-infected patients, accounting for approximately one-third of the deaths.

    One cancer that has been increasingly substantially in HIV-infected individuals in the United States and other areas where cART is available is anal cancer. In addition, there has been an increase in the incidence and prevalence of pre-cancerous anal lesions. HIV-infected patients with human papillomavirus (HPV) infection are more likely to have persistent HPV infection and develop precancerous lesions than HIV-uninfected individuals. Also, these patients are less likely to have lesion regression, and more likely to have disease recurrence after standard lesion ablation therapy. Although cART seems to improve tolerability of more aggressive therapy for anal disease in HIV+ patients, toxicity and relapse continue to be a problem and cART seems to have little effect on the natural history of established lesions. Overall, there is a substantial and increasing need for improved prevention and treatment of tumors in HIV-infected patients. Moreover, there is a substantial need for approaches to these tumors as well as other tumors caused by HPV that are appropriate for resource-limited regions.

    Given these needs, it is extremely important that a clinical trials program be structured to evaluate and optimize clinical interventions for the treatment and prevention of HIV-associated cancers in the United States as well as resource-limited regions. Such a program should optimally involve investigators with substantial expertise in HIV/AIDS-related malignancies and should include correlative laboratory studies aimed at gaining a better understanding of cancer pathogenesis and parameters related to disease progression and response to treatment.  In addition, it is important to support studies on the impact of cART on the pharmacokinetics of the anti-cancer chemotherapy, on toxicity profiles, and the response to treatment.

    Objectives and Scope:

    The overarching goal for the Consortium is to continue its domestic and international efforts to develop more effective prevention and treatment strategies for cancers associated with HIV/AIDS. It is expected that the geographical distribution and composition of the clinical trial sites (CTS) will reflect geographical areas with high HIV/AIDS disease burden.

    Scientific approaches taken by the Consortium will continue to be broad in scope and will reflect the creativity and capabilities of team participants. Broad areas of study include translational research, optimization of clinical management and cancer prevention studies including those of risk and cancer susceptibility.

    The AMC will evaluate clinical interventions for treatment and prevention of cancer in HIV-positive patients, investigate the biology of these malignancies in the context of clinical trials, and donate specimens and clinical data to the AIDS and Cancer Specimen Resource (ACSR) (https://acsr.ucsf.edu/). In the case of pilot, Phase I, or Phase II clinical trials, laboratory studies to monitor patients (e.g., pharmacokinetics, pharmacodynamics) or to measure a particular biological response (e.g., imaging) that may provide information relevant to the interpretation of the success or failure of the therapy administered are encouraged. Tissue specimens and/or biological fluids are expected to be collected for: AMC genomic and biomarker laboratory studies; donations to the ACSR; and NCI Office of HIV and AIDS Malignancy(OHAM, https://www.cancer.gov/about-nci/organization/oham)-supported projects or projects OHAM has identified as programmatically important for the NCI AIDS malignancy effort.

    The research agenda of the consortium is encouraged to include cancer survivorship and quality of life research as applicable.  It is expected that the research of the AMC will focus on HIV-infected individuals and be aligned with the criteria for AIDS research as defined by the NIH Office of AIDS Research, https://www.oar.nih.gov/. This research may include however, a limited number of HIV-uninfected patients as controls to optimally study the tumors that most commonly develop in the context of HIV infection.

    It is expected that the AMC will substantially expand their international agenda particularly in Sub Saharan Africa and Latin America. This expansion is warranted to meet the challenges and the needs of these locales and to find scientific solutions to improve the standard of care of HIV patients with AIDS-related malignancies. This is expected to be accomplished by involving foreign investigators cooperatively in identifying the scientific issues to be addressed, capacity building, appropriate designs of treatment and prevention trials as needed.

    The AMC biobanking needs for clinical trial support (excluding the ANCHOR trial) will be supported by the ACSR.

    Examples of research directions that may be pursued include (but are not limited to):

    A) AIDS Defining Cancers:

    Kaposi’s sarcoma (KS): Despite the dramatic effects that cART had on the incidence of KS, the tumor continues to be the most commonly diagnosed tumor in HIV-positive patients. To date, there is not an accepted standard of care policy for patients on cART with well controlled HIV infection who develop KS. Research on KS is needed in the following areas:

    • Evaluation of pathogenesis-based approaches for treatment of KS including approaches that target virus-driven, host-directed processes, HHV-8 viral gene targets, angiogenesis or a combination thereof;
    • Management in pediatric patients with HIV and cancer;
    • Evaluation of new classes of molecules with unique and improved features such as better pharmacologic or toxicological properties;
    • Integration of immune-based therapeutic approaches in treatment regimens;
    • Identify new strategies for the treatment of KS-related fibrosis, including lower extremity edema;
    • Refinement and evaluation of more precise methods for KS tumor assessment;
    • Development and refinement of biomarkers for tumor responses that can predict the progression of the natural history of the disease and response to treatment; and
    • Evaluation of new hypotheses generated from pathogenesis studies.

    Non-Hodgkin’s Lymphoma (NHL): HIV-infected individuals are at increased risk for developing NHL. Although cART dramatically decreased the incidence of primary central nervous system lymphoma, conflicting results have been reported for systemic lymphoma. Though the introduction of cART has improved patient survival substantially, the standards of care for NHL have not been fully optimized in the HIV/AIDS setting. Areas of interest may include:

    • Novel pathogenesis-driven therapeutic approaches including relapsed and/or refractory lymphoma;
    • Integration of immune-based therapeutic approaches to treatment regimens;
    • Identifying and testing biomarkers to identify predictors of response to interventions in symptom management;
    • Identifying and testing biomarkers that will identify predictors of cancer risk;
    • Identification of host determinants that influence response to therapy;
    • Elucidation of biological determinants of tumor sensitivity/resistance to therapeutic interventions; and
    • The effects of therapy on the host innate and adaptive immunity to HIV and EBV as they may affect long-term toxicities and tumor responses.

    Cervical cancer: Despite that the incidence of cervical cancer in the general population has been

    decreasing in the last 15 years, it has not changed substantially among HIV-seropositive women. The prevalence of HPV infection in HIV-positive women is more than twice that in HIV-negative women. Treatment failure and recurrence are common among HIV-infected women. Cervical cancer continues to be a major problem in developing countries particularly those in sub-Saharan Africa. Addressing the scientific research needs for optimizing prevention, and treatment of cervical cancer in women in those countries is warranted. Areas of interest may include:

    • Optimization of chemoradiotherapy for advanced stages of cervical cancer in HIV-infected women;
    • Optimization of management of different disease stages in the context of antiretroviral therapy;
    • Determination of optimal cervical cancer prevention strategies;
    • Determination of the biologic and molecular interactions between HIV and HPV that might influence the natural history of the lesions; and
    • Evaluation of novel anti-HPV therapies such as check point inhibitors, therapeutic vaccination or adjuvants to surgical treatments to improve long term outcomes.

    B) Non-AIDS defining cancers:

    Anal cancer and its precursors: HIV-infected patients are at increased risk for developing anal cancer as compared to the general population. Anal high-grade squamous intraepithelial lesion (HSIL) is a precursor of anal cancer that can be treated.  However, detection and treatment of anal HSIL are challenging; and treatment-associated morbidity and relapses are common among HIV-infected patients. cART seems to have a little effect on the natural history of these lesions.

    • Development of successful treatment and prevention strategies for anal HSIL;
    • Development of novel approaches for prevention of progression of anal HSIL to cancer;
    • Development of effective and well tolerated treatment options for anal HSIL and/or anal cancer including immunotherapeutic approaches such as therapeutic vaccination and check point inhibitor therapy; and
    • Determining the genetic, immunologic, and virologic correlates of these lesions.

    Head and Neck Cancers (HNSCC): People with HIV infection are at elevated risk for HNSCC. The risks of cancers of the tongue, tonsil and oropharynx are greater than expected among HIV-infected individuals in the U.S. and elsewhere. Both molecular and epidemiological data indicate a strong and consistent association between HPV and cancers that arise from the lingual and palatine tonsils within the oropharynx. HPV16 accounts for the overwhelming majority (90-95%) of HPV-associated cases of such cancers. Therefore, it is necessary to:

    • Evaluate the effectiveness of novel therapeutic strategies;
    • Identification of biomarkers that may predict cancer risk; and
    • Testing different methods of diagnosis and early detection.

    Hodgkin’s Disease (HD):

    • Optimization of the treatment strategies of HD in the HIV setting; and
    • Elucidation of biological determinants of tumor sensitivity/resistance to therapeutic interventions.

    Other non-AIDS-Defining-Cancers: Other cancers that have been reported to increase among people living with HIV in the era of cART include lung cancer, hepatocellular carcinoma and ocular surface squamous neoplasia, OSSN.

    • The management of these cancers in the HIV setting needs to be optimized;
    • Identifying the factors associated with the risk and susceptibility to these cancers:
    • Testing screening technologies aimed at reducing cancer risk

    C) Other Aspects of Interest

    Clinical Pharmacology: The NCI has several initiatives aimed at removing barriers to general cancer trial participation among HIV-infected patients. These initiatives focus mainly on non-AIDS-defining cancers. However, the success of such initiatives requires a clear understanding of the issues related to drug-drug interactions between anticancer agents and antiretroviral therapeutics, including pharmacologic interactions. As such, the following area of investigation needs to be emphasized:

    Evaluation of pharmacokinetic interactions of antiretroviral agents and novel and established anti-cancer agents used for treating HIV/AIDS-related and non-HIV/AIDS-related malignancies.

    Cancer Survivorship: The number of cancer survivors in the United States is expected to increase significantly with the aging of the United States population and the improvement in the management of people living with HIV infection. Cancer survivors may experience a host of long-term and late effects of cancer and cancer therapy and many comorbid conditions that require coordinated follow-up care after completion of primary treatment for cancer. The following area of investigation needs to be emphasized:

    • Evaluation of late complications, health status, and factors affecting quality of life in cancer survivors, especially those who have been on AMC protocols.
    • Evaluation of social determinants and barriers of access to health care and treatment that will affect the outcome and quality of life of cancer patients living with HIV infection.

    AMC Operation in International Settings: 

    The conduct of international collaborative work into sub Saharan Africa, Latin America and other low- and middle-income countries on other continents is vital for epidemiologic, basic, and clinical research in populations with high prevalence of KS, NHL and cervical cancer and other HPV-related neoplasia. It is expected that the AMC will:

    • Continue to expand their research agenda in sub-Saharan Africa and Latin America;
    • Develop studies that address research questions aligned with the needs of these communities;
    • Develop a research agenda focused on enhancing our knowledge of the host, genetic, and viral factors involved in cancer development that will eventually guide improving upon the current standards of care in these populations;
    • Involve the international investigators in developing the AMC international research agenda and take leadership roles in AMC activities; and
    • Provide professional development and capacity building for foreign site personnel.
    Consortium Organization

    The AIDS Malignancy Consortium must include the following functional units:

        1. AMC Chair Administrative Office (Administrative Core);

        2. Operations Center;

        3. Research Program based on disease-oriented scientific Working Groups;

        4. Domestic Clinical Trials Sites (Domestic and International)

        5. AMC Core Resource Laboratories; and

        6. Statistics and Data Management Center.

    The AMC Chair is expected to be Program Director/Principal Investigator (PD/PI) of the applicant institution. AMC Chair will be responsible for ensuring that the AMC’s major structural components are capable of carrying out their respective responsibilities and that they operate in a well-coordinated fashion. The AMC Chair will be responsible for the scientific integrity, productivity, governance, and fiscal accountability of the group.

    The Operations Center is expected to provide administrative leadership, central operations, communications, and monitoring of domestic and foreign clinical trials sites, including those involved in the ANCHOR trial.

    Research Program of the AMC is to be based on the disease-oriented scientific Working Groups. Each Working Group is expected to include member investigators of appropriate profile from AMC clinical trial sites. These Working Groups will contribute to the ongoing refinement of the Network scientific research plan and oversee the development and implementation of clinical trial protocols in their respective areas. The research activities of each Scientific Working Group are expected to include efforts to develop international clinical trials. The international research agenda should address the needs of resource-limited countries (primarily in Africa and Latin America) for a specific disease area.

    Domestic and International Clinical Trial Sites must be able to efficiently and effectively enroll subjects for the clinical research, contribute to the AMC scientific research agenda, and engage in capacity building.

    AMC Core Resource Laboratory will be responsible for performing standard testing of various parameters needed for the correlative studies pertaining to clinical trials and preclinical drug screening functions and will work closely with the ACSR network which will be providing tumor banking support for AMC trials.

    The AMC Statistical and Data Management Center must be able to provide biostatistics leadership and central data management capabilities for the AMC clinical research.

    AMC Governance

    AMC will be led by the AMC Chair with assistance of the Executive Committee for the daily operations.

    Scientific Planning Committee (SPC): In terms of overall strategies and direction, the Consortium will be governed by the SPC. The primary function of the AMC SPC will be to define research directions of the AMC and to assure that the clinical research procedures for the AMC are: (a) sufficient to meet the program objectives; (b) sufficient to protect participants enrolled on AMC studies; and (c) are being followed in the execution of the AMC clinical activities.

    For details on the composition and functions of the Executive Committee and Scientific Planning committees, see Section VI.2. Cooperative Agreement Terms and Conditions of Award.

    Program Evaluation

    The program under which the AMC is funded will be subject to external evaluation near the end of the third year of the funding period (to be coordinated by the NCI Program Staff). Such evaluation is part of NIH efforts to optimize the efficiency of the funded research. The evaluation process will involve monitoring and assessing the progress of the AMC toward achieving its goals. This aspect includes evaluating the quality, value, and scientific impact of the research conducted by the Consortium.

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

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

    Application Types Allowed

    Renewal of previous award under RFA-CA-14-502.

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

    Clinical Trial?

    Required: Only accepting applications that propose clinical trial(s)

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NCI intends to commit $24 million in fiscal year 2020 to fund one award. Future year amounts will depend on annual appropriations

    Award Budget

    The application budget needs to reflect the actual needs of the proposed Consortium but must not exceed $24 million for year one, with a total 5-year cost not to exceed $114 million.

    Award Project Period

    A project period of 5 years must be proposed.     

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

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Only the current awardees of the AIDS malignancy Consortium supported under RFA-CA-14-502are eligible to apply to this FOA, with the provision that the applicant team may choose, which of the participating institutions will serve as the seat of the AMC Operations Center and as application-submitting institution.

    Foreign Institutions

    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.

    Required Registrations

    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)– 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.
    • 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 to register in eRA Commons.  Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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.

    Eligible Individuals (Program Director/Principal Investigator)

    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.

    A PD/PI from the application submitting institution is expected to be designated as AMC Chair.

    2. Cost Sharing

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

    3. Additional Information on Eligibility
    Number of Applications

    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).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

    2. Content and Form of Application Submission

    It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

    Letter of Intent

    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:

    Mostafa Nokta, M.D., Ph.D.
    National Cancer Institute (NCI)
    Fax: 240-541-4520
    Email: Noktam@mail.nih.gov

    Page Limitations

    All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

    The Research Strategy must consist of the following sub-sections with the indicated page limits:

        A. AMC Overview: one required ─ 12 pages

        B. AMC Chair Office: one required ─ 6 pages

        C. Operation Center: one required ─ 6 pages

        D. Research Program: one required ─ 12 pages

        E. Clinical Trial Sites: one required ─ 12 pages

        F. Network Resource Laboratory: one required ─ 6 pages

        G. Statistics and Data Management Center: one required ─ 6 pages

    Instructions for Application Submission

    The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

    SF424(R&R) Cover

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

    SF424(R&R) Project/Performance Site Locations

    All instructions in the SF424 (R&R) Application Guide must be followed. Each Clinical Trial Site must be able to efficiently and effectively enroll subjects/patients in the clinical trials, contribute to the Consortium scientific capabilities, and engage in capacity building at less well-developed clinical research sites.

    Each International Clinical Trial Site must be able to efficiently enroll subjects to clinical research studies, to be conducted by the Network and contribute to the international research agenda of the AMC.  

    SF424(R&R) Other Project Information

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

    Facilities & Other Resources:

    For each Clinical Trial Site proposed, provide documentation demonstrating the scientific expertise and capacity to conduct clinical research on AIDS-related malignancies. For each clinical research site provide information on: the infrastructure for the research proposed such as clinical, laboratory, pharmacy, and space for document storage; available resources for routine laboratory testing, such as safety laboratories; facilities for processing and storage of blood and other clinical specimens; and institutional support for the conduct of clinical research under U.S., DHHS, and NIH regulations and policies regarding human subjects.   

    Other Attachments:

    Applicants must provide the following additional materials specified below in support of their application.

    Each attachment must be uploaded as separate PDF files. The filename provided for each attachment will be the name used for the bookmark in the application image.

    Attachment 1: Organizational Data. Provide the following information as a PDF file with the name “Organizational Data”:

    • Table of content of the attachment
    • Flow chart with the organizational structure, leadership, management/administration, scientific Working Groups and committees—etc.
    • Summary Table for Scientific and Laboratory Working Groups and the International Committee. In the table, list all members of respective groups. Include columns for member’s affiliation and fields of expertise. Other critical characteristics may also be listed, if appropriate.
    • Summary Table of Domestic Clinical Trial Sites. For each site/institution, include the most relevant site characteristics.
    • Summary Table of International Clinical Trial Sites. For each site/institution identify city and country) and include the most relevant site characteristics.
    • AMC process for selecting new clinical sites as "members".
    • The process for application and selection of AMC junior investigator trainees.

    Attachment 2: Accomplishment Data. Provide the following information as a PDF file with the name “Accomplishments”:

    • Table of content of the attachment;
    • Summary of the consortium’s most impactful and practice-changing accomplishments relative to HIV+ patients with cancer;
    • Summary Tables for completed, active and in development domestic clinical trials by disease area (for years 2015-2019;
    • Summary Table for completed, active and in development International Clinical Trials (2015-2019);
    • Summary Table for completed AMC Trials (pre-2015);
    • Summary Table for clinical trials collaborations with other NIH-supported groups;
    • Summary Table listing letters of intent (submitted and approved by CTEP) and clinical trials protocols submitted (for years 2015-2019);
    • Accrual Summary Table (for years 2015-2019);
    • Summary Table for the ANCHOR Participating Sites. Include columns for lead investigator, date of site certification and subject accrual including numbers of screened and randomized subjects.
    • Summary Table for demographics of the ANCHOR trial participants including gender race /ethnicity composition;
    • Summary Table providing data on annual Domestic patient accrual to AMC trials by gender and race/ethnicity composition (for years 2015-2019); and
    • Summary Table for carrier enhancement activities during the period from 2015-2019, with such information as names of trainee-investigators and mentors, affiliations, and areas of training.

    Attachment 3: Protocol Development:  Provide the following information as a PDF file with the name “Protocol Development”:

    • AMC Protocol Development process
    • Protocol Intensity Scoring

    Attachment 4: Site Performance: Provide the following information as a PDF file with the name “Performance Evaluation”).

    • Standard operating procedures (SOPs) used for AMC Site Performance Standards and Measures
    • Procedures for addressing remediation and defunding poorly performing sites

    Attachment 5: Strategic Planning Process. Provide the following information as a PDF file with the name “Strategic Planning” (not to exceed 2 pages)

    • Outline the process for strategic planning of the research agenda for the consortium relative to prioritization of research related activities (e.g. cancer therapy trials, correlative biology/genomics, cancer prevention/intervention trials, cancer survivorship)

    Attachment 6: Clinical Trial Sites. Provide the following information as a PDF file with the name ”Clinical Trial Sites”:

    • Summary Table for participating Clinical Trial Sites. Include columns for the site name, site Clinical Director and protocols opened. Other critical characteristics may also be listed, if appropriate.
    • Use separate tables for domestic and international sites.

    Attachment 7: Data for Network Resource Laboratory. Provide the following information as a PDF file (use filename “Data for Network Resource Laboratory”):

    • Table of content of the attachment
    • Organizational chart for the Network Resource Laboratory and its specialized Core units;
    • Chart for specimen flow across AMC clinical trial operation;
    • Summary Table for AMC sample donations to the AIDS and Cancer Specimen Resource (ACSR) (2015-2019);
    • Summary Table for samples processed by each of the Core units, indicating the nature of the assay and related studies (2015-2019); and
    • AMC Laboratory Quality Assurance process.

    Attachment 8: Statistics and Data Management. Provide an organizational flow chart for the Statistical and Data Management Center (use filename "SDMC Organization").

    SF424(R&R) Senior/Key Person Profile

    All instructions in the SF424 (R&R) Application Guide must be followed.  Each Clinical Trial site must also have a designated Clinical Director. Clinical Directors should have appropriate leadership skills, expertise, and experience (documented by their scientific contributions) to ensure their abilities to design, prioritize, and conduct required research activities. All proposed Domestic and International Clinical Trial Sites should have appropriately skilled clinical investigators.

    Biographical Sketches: In addition to standard content, as appropriate for individual researchers, include in the Biographical Sketches under "Personal Statement" the following:

    For each individual designated as a Clinical Director of a domestic or international Clinical Trial Site, summarize this individual's:

    • ·    Major strengths, critical experience, and scientific contributions relevant to the design and conduct of AMC clinical trials;
    • ·    Ability to lead, contribute to, and prioritize research activities; and
    • ·    Capacity to conduct AIDS-related malignancies clinical research.

    For each individual designated as a Director of AMC Laboratory Core unit, summarize this individual's: experience with performing standard testing of various parameters needed for the correlative studies pertaining to clinical trials and/or preclinical drug screening functions.

    For the individual designated as the Director of the Operations Center, describe this individual's critical operational experience with managing multi-center clinical trials networks.

    For the individual designated as a Director of the Statistical and Data Management Center, outline the relevant expertise for the statistical and data management support of the AMC clinical research plan.

    R&R Budget

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

    In the budget justification, provide budget breakout for the following categories:

    • Conduct and management of the ANCHOR trial. A sum of up to approximately 58% of the total budget requested in year one may be allocated for ANCHOR activities, including biobanking and support of investigators meetings. This amount should include an ANCHOR Trial Patient Care Support Fund (approximately $3,000,000 total cost). The budget request for this Fund should cover costs for patient care screening, high-resolution anoscopy, reimbursement to patients for transportation, and treatment modalities. The cumulative budget allocated for the ANCHOR trial during the entire project period cannot exceed $60.8 million in total costs.
    • Basic AMC Site Support (approximately 7.6% of the requested budget):  Applicants may propose expenses to support an appropriate number of domestic Clinical Trial Sites. The budgetary request should include per capita costs of accrual for four to six patients per site/year depending on the intensity of the protocol. Additional support for sites participating in the ANCHOR trial is permitted.
    • Foreign Site Budget (approximately 8.5% of the requested budget): Applicants may propose expenses for basic site support for up to 12 foreign institutions.  The budgetary request may include costs of personnel, travel, training, and capacity building and compensation for the leadership of the International Program.
    • Protocol Implementation Fund (approximately 6.7% of the requested budget): The budget request for this Fund may include costs of per capita patient accrual, protocol-mandated drug purchases, storage, and distribution for international trials, costs for laboratory diagnostics not reimbursed as standard of care, clinical trial insurance, computerized tomography (CT) scans, remote audits of radiotherapy machine output and on-site dosimetry review audits for international trials.
    • AMC Clinical Trial Research Fund (approximately 3.5% of the requested budget): The budget request for this Fund should cover costs of support for AMC Resource Laboratory, Clinical Pharmacology and Correlative studies.
    R&R Subaward Budget

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

    PHS 398 Cover Page Supplement

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

    PHS 398 Research Plan

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

    Specific Aims: Outline the general strategic objectives for the AMC and the plan to achieve these goals.

    Research Strategy: Research Strategy must consist of the sub-sections A-G described below, uploaded as single PDF attachment:

    Sub-section A. AMC Overview

    Briefly outline the vision and proposed goals for AMC. Include your understanding of the opportunities and challenges for multidisciplinary clinical research on AIDS-related malignancies and strategy for domestic and international clinical studies (particularly in resource-limited countries).

    Define organizational and governing structure, lines of authority, and decision-making processes. Describe how the AMC units will interact to address specific scientific research priorities of the AMC Program. Discuss how the special features of the Consortium environment and resources will create unique opportunities to serve the AMC scientific goals and career enhancement activities for junior investigators. Indicate any major organizational changes proposed for the Consortium renewal.

    Progress Report. In this Sub-section, summarize also AMC progress in the current funding period. In addition to standard instructions for Progress Report, address the following elements:

    • Major accomplishments during the current funding period;
    • Overview of clinical trials conducted, including the ANCHOR trial;
    • Progress of the ANCHOR trial performance, choice and certification of performance sites, and patient accrual and demographics; and
    • New resources/capabilities established as a result of AMC award and collaborations with other NIH/NCI clinical trial infrastructures.
    • Career enhancement research activities of junior investigators

    Note: Supporting documentation for this sub-section is requested under "Other Attachments" (Attachments 1 and 2).

    Sub-section B. AMC Chair Office

    In this section, describe the infrastructure in support of the required administrative activities of the AMC Chair including, but not limited to the leadership of the Executive Committee, the logistics and organizations for various meetings, site visits, preparation of required reports, etc.

    • Describe protocol development and prioritization process
    • Career enhancement plans for junior investigators: describe plans to incorporate new, minority, and junior investigators into the Network's research activities
    • Outline activities intended to increase the role of patient advocate/patient community in AMC.

    The applicants are encouraged to designate a vice-chairperson, who would be capable of leading the Executive Committee and the entire AMC in the event that the chairperson is unable to continue serving in this role. Provide rationale for the selection of both AMC Chair and vice-chairperson.

    Note: Supporting documentation for this sub-section is requested under "Other Attachments" (Attachment 3).

    Sub-section C. Operations Center

    The Operations Center is expected to provide administrative leadership, central operations, communications, and monitoring of domestic and foreign clinical trials sites, including those involved in the ANCHOR trial. Describe the organizational structure, including lines of authority, decision-making processes, policies and procedures for Consortium communication, committee support, protocol development, implementation and mandated-regulatory monitoring of clinical trial sites.

    Performance Evaluation. Describe criteria and processes for ongoing evaluation and problem resolution of all Consortium components and criteria for defunding poorly performing clinical trial sites.

    Note: Supporting documentation for this sub-section is requested under "Other Attachments" (Attachment 4).

    Sub-section D. Research Program

    • High Priority Research Areas. Summarize the ongoing research, and articulate the vision of the AMC and the scientific research agenda of the applicant team for the proposed funding period. The proposed research plan may include the continuation of ongoing clinical trials, with appropriate rationale and brief discussion of how those studies contribute to the proposed research program. Indicate those understudied/underappreciated areas of the management of HIV-related cancers for which AMC efforts may be unique or prevalent.
    • Provide plan/steps currently in place or that will be implemented to increase the rate of accrual on clinical trials.
    • Scientific Working Groups. Define disease-specific Working Groups and describe their intended activities and future directions. Outline how these groups will contribute to the ongoing refinement and updating of the AMC research goals, oversee protocol development and implementation, and ensure timely publication of study results. The number of Working Groups and the applicable scientific areas involved must be based on the scientific activities of the Network and reflect the patterns of malignancies that occur among individuals with HIV infection. The Working Groups will need to have an efficient structure with the necessary expertise. New Scientific Working Group(s), if any, need to be described in terms of their research agenda and the plans for implementation and achievement of those objectives. The description of Scientific Working Groups needs to include their current and/or future international research efforts particularly in Africa and Latin America.
    • Management of the ANCHOR clinical trial. The AMC is currently conducting a large randomized trial (the “ANCHOR” study), and successfully completing this study will be an important part of the AMC activities. Given the size and complexity of the ANCHOR study, describe coordination, implementation and ongoing efforts to complete accrual and ensure study subject adherence and retention to the trial.
    • Correlative Research Agenda. Describe the correlative science research agenda for the group.
    • Cross-Network Collaborations. Outline how the AMC expects to interact with other NIH-sponsored HIV/AIDS programs and other NCI-supported research networks to achieve the AMC aims and objectives.
    • Overall Requirements for AMC Clinical Trial Sites. Identify the approximate number and capacity of the clinical research sites the Consortium will require to efficiently and effectively implement the proposed domestic and international clinical research agenda. Describe the criteria and process used to select them.
    • Community Advisors.  It is expected that the AMC will work closely with local patient advocacy groups and institutional community advisory boards. Describe the organizational structures and Consortium policy and procedures for ensuring community input and community representation within the Consortium.

    Note: Supporting documentation for this sub-section is requested under "Other Attachments" (Attachment 5).

    Sub-section E. Clinical Trials Sites

    Under separate subheadings describe Domestic and International Clinical Trial Sites addressing the following aspects:

    Part 1: Domestic Clinical Trials Sites

    A Domestic Clinical Trial Site is expected to accrue a minimum of four patients on clinical trials per year in any of the following disease areas: KS; lymphomas; and NADCs. HPV-related premalignant disorders can also contribute to the minimum site accrual target (albeit two such patients will count as a single accrual towards the fulfillment of the recruitment quota). New sites must be able to initiate subject recruitment within the first 6 months of award.

    Explain how these requirements will be met by specifically addressing the following:

    • The rationale for selecting each clinical research site (in the context of site's expertise and experience in AIDS malignancy clinical research);
    • Accomplishments of each site in AIDS-related cancer clinical research and past performance in multicenter clinical trials;
    • Summary of the active involvement of Site investigators in AMC activities, including service on committees, Working Groups, and group efforts to develop clinical trial protocols; and
    • Site expected contribution to AMC, including recruitment of clinical trials subjects.

    Part 2: International Clinical Trials Sites

    Address the following:

    • The rationale for selecting each clinical research site (in the context of the site's expertise and experience in AIDS malignancy clinical research); and
    • The expected contribution of each site to AMC research and accrual potential for clinical trials.
    • Training and capacity building

    Note: Supporting documentation for this sub-section is requested under "Other Attachments" (Attachment 6).

    Sub-section F. Network Resource Laboratory

    The Network Resource Laboratory (NRL) must be capable of performing standard testing of various

    parameters needed for the correlative studies pertaining to clinical trials and preclinical drug screening functions. The laboratory, operating through its specialized Core units, must use standard good laboratory practice techniques and must maintain a quality assurance/quality control program that will ensure the integrity of the data generated.

    In this section, describe the following:

    • Management plan for the Network Resource Laboratory and its specialized Core units.
    • Address areas of competence and responsibility of each Core unit. The number and types of Core units should relate to projected type, size and complexity of the proposed Consortium clinical research protocols.
    • Laboratory expertise and competence that will be available to serve the needs of the Consortium Research Program.
    • Procedures for communication across the NRL (among its Core units) as well as with other Consortium parts.
    • Procedures for conducting and reporting laboratory studies in the areas necessary to the Consortium clinical research plan, including:(i) procedures for collection, testing, tracking, storage and retrieval of laboratory specimens; and (ii) quality assurance and quality control procedures; (iii) a method for interfacing with Network Statistics and Data Management Center (SDMC) for tracking laboratory specimens and merging laboratory data with clinical data.
    • Interaction with the AIDS and Cancer Specimen Resource and AMC/ACSR biorepository.
    • Biospecimen collection and banking for the ANCHOR trial.

    Note: Supporting documentation for this sub-section is requested under "Other Attachments" (Attachment 7).

    Sub-section G. Statistics and Data Management Center (SDMC)

    The Statistical and Data Management Center must be able to provide biostatistics leadership and central data management capabilities for the AMC clinical research, including the ANCHOR trial.

    In this section, describe the following:

    • Operational, procedural, and overall management plans for the SDMC.
    • Biostatistics and data management approaches planned to be used in AMC multi-site clinical trials.
    • Any innovative aspects and plans relevant to data collection, processing, statistical workout and data integration, quality control, data related to the safety of the patients, etc.    
    • Proposed procedures for managing both clinical and laboratory data, including database architecture and plans for improvements of the relevant aspects of the information technology system used.

    Note: Supporting documentation for this sub-section is requested under "Other Attachments" (Attachment 8).

    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.

    Appendix:

    Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

    PHS Human Subjects and Clinical Trials Information

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) 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 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 should not propose any specific clinical trials at the time of application, Study Record should NOT be completed.

    Delayed Onset Study

    Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

    Complete the Delayed Onset Study record and must check box "Anticipated Clinical Trial?"

    Study Title-- use:  "Multiple Delayed Onset Studies"

    Justification Attachment:  Indicate that the clinical trials will be designed and conducted by the AMC during the Project Period. Each clinical trial protocol developed will be subject to approval through the standard NCI procedure that involves an initial concept submission and subsequent review.  If the concept receives approval, the next stage will be development of the protocol, which also must undergo review and approval by NCI/DCTD Clinical Trial Evaluation Program, prior to activation through the AMC network. Indicate areas of oversight, regulatory compliance monitoring, etc. that will be the responsibility of the AMC.

    PHS Assignment Request Form

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

    3. Unique Entity Identifier and System for Award Management (SAM)

    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

    4. Submission Dates and Times

    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). 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.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

    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.

    7. Other Submission Requirements and Information

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

    Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

    For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

    Important reminders:

    All PD(s)/PI(s) 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. See Section III of this FOA for information on registration requirements.

    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. 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.

    Post Submission Materials

    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.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process.

    Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

    For this particular announcement, note the following:

    As this FOA is to support the essential AMC clinical trials infrastructure, reviewers will assess to what degree the proposed Research Base will be able to fulfill all the required functions, including rigorous study design, focus on interventions that address clinically important questions or unmet needs.

    The emphasis of this FOA is on the ability of the proposed Consortium to provide strong, competent, and comprehensive scientific and statistical leadership for developing, implementing, and analyzing multi-institutional cancer treatment and prevention clinical trials domestically and internationally in the context of HIV. Integration of individual functional components, the ability to adapt their research agenda to reflect the state of the cancer burden in HIV positive individuals, and the ability to overcome the challenges of conducting international trials are particularly important.

    A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but 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.

    Overall Impact

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

    Scored Review Criteria

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

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 

    Are the 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?

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? 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: Is the justification for the selection of AMC chair and vice chair sufficiently strong? Is the selection of consortium investigators adequate to the AMC goals? How well does the entire consortium represent a team with broad multidisciplinary expertise in HIV management, management of oncologic morbidities that are common in the HIV-infected patients? To what degree do the investigators show understanding of the opportunities and challenges in conducting international U.S.-supported clinical studies, particularly in resource-poor countries? How strong is their experience in collaborating with other NIH/NCI clinical trial infrastructures relevant to AMC? Do the identified Working Group Chairs have sufficient expertise and abilities to lead specific disease area Working Groups?    

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?  

    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?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? 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 project 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 individuals of all ages (including children and older adults), 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:

    Organizational and governing structure

    Is the organizational and governing structure proposed by the applicants adequate for the mission of the AMC? and are the lines of authority and decision-making processes sufficient? Do the AMC units and their interactions as proposed address the specific scientific research priorities of the AMC Program? Are the special features of the Consortium environment and resources reasonable to create unique opportunities to serve the AMC scientific goals and career enhancement activities for junior investigators? Are the organizational changes proposed for the Consortium renewal reasonable?

    Research Program and Clinical Trial Sites

    • ·     Have the proposed clinical studies been judiciously selected so as to make major contributions to the management of HIV-related cancers and other cancers developing in HIV-infected individuals, where these contributions are unlikely in the absence of the AMC?
    • ·     Are the structure and number of committees and Working Groups appropriate and well selected?
    • ·     Will these Working Groups contribute to the ongoing refinement of the AMC research goals, oversee protocol development and implementation, and ensure timely publication of results?
    • ·     To what degree have the proposed studies leveraged other existing clinical trial structures in developing cancer related studies?
    • ·     To what extent is the vision of international studies relevant to the needs of the population?
    • ·     Are the efforts toward developing international clinical trials sufficient?
    • ·     Are the proposed criteria and evaluation metrics of the clinical trial sites reasonable and sufficient?
    • ·     Are the proposed procedures for implementing required actions for inadequate performance of sites and /or laboratories adequate?
    • ·     How appropriate are the criteria and processes for ongoing evaluation and problem resolution of all Consortium components and criteria for defunding poorly performing clinical trial sites?
    • ·     For each proposed clinical trial site: How well does the individual site fit into the AMC structure? Does this site have all the required capabilities to meet the accrual goals specified in the FOA?
    • ·     Statistics and Data Management Center
    • ·     Are the statistics and data management structure and leadership of the Statistics and Data Management Center adequate?
    • ·     Are the plans to collect, monitor, and analyze the data and assure the safety of the patients sufficiently developed?
    • ·     The “ANCHOR” study: Given the size and complexity of the ANCHOR study, are the coordination, implementation and ongoing efforts to complete accrual adequate? and are the proposed efforts to ensure study subject adherence and retention to the trial reasonable?
    • ·     Is the correlative science research agenda for the group adequate?
    • ·     Are cross-network collaborations with other NIH-sponsored HIV/AIDS programs and other NCI-supported research networks to achieve the AMC aims and objectives reasonable?
    • Are the AMC Consortium policy and procedures for ensuring community input and community representation within the Consortium adequate?

    AMC Chair Office

    • ·     Are the AMC Chair and members of the EC sufficiently effective in terms of increasing patient accrual? How appropriate are the plans for the protocol development and prioritization process? Are the proposed steps to include new and junior investigators in AMC activities sufficient? Are the activities of the AMC Chair and members of EC adequate to increase patient advocate/patient community involvement?

    Operations Center

    • ·     How well will the Operations Center serve the needs of AMC in terms of coordinating multiple facets of the AMC clinical trials? Will the proposed organization and procedures ensure the efficiency of the Operation Center?

    Network Core Laboratories

    • ·     Are the Network Resource Core Laboratories appropriate and sufficiently justified? Will they provide the required resources in all specified areas?
    Environment

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

    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? 

    Additional Review Criteria

    As applicable for the project 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)?

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the 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  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.

    Inclusion of Women, Minorities, and Individuals Across the Lifespan 
     

    When the proposed project 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 individuals of all ages (including children and older adults) 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.

    Vertebrate Animals

    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.

    Biohazards

    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.

    Resubmissions

    Not Applicable

    Renewals

    For Renewals, the committee will consider the progress made in the last funding period.

    Revisions

    Not Applicable

Additional Review Considerations

As applicable for the project 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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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).

Resource Sharing Plans

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 (GDS).

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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:

  • 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.
3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information
1. Award Notices

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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that 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). 

2. Administrative and National Policy Requirements

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html.  Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.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 (DHHS) 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 primary responsibility for:

  • The Principal Investigator (or multiple PDs/PIs, if applicable) will have the primary responsibility for strategic planning and to define the objectives and approaches needed to conduct, analyze, and publish results, interpretations, and conclusions of the studies conducted. Specific responsibilities of PD/PI, awardee institution, and other key personnel are defined below.
  • The AMC Group Chair will oversee the development of the clinical and laboratory research design, including definition of objectives and approaches, planning, implementation, analysis, and publication of results, interpretations, and conclusions of studies. The Network will continue to develop pilot, Phase I, Phase II, and Phase III protocols in accord with the research interests, abilities, and goals of the Network, and submit them to CTEP for review prior to their implementation.
  • The AMC Group Chair with the assistance of the Operations Center, and the Executive Committee (EC), is responsible for coordinating protocol development, protocol submission, study conduct, quality assurance including quality control and study monitoring, data management, statistical design and analysis, protocol amendments/status changes, adherence to requirements regarding investigational drug management and federally mandated regulations and protocol and performance reporting. Specific responsibilities are listed below.
  • Organization Structure, By-Laws, Standard Operating Procedures (SOPs) and Evaluation Criteria: The Group Chair and the Executive Committee, with support from the Operations Center, are responsible for development and maintenance of an organizational structure for the AMC, including a charter/by-laws for the Group. The organizational structure should include the Scientific Working Groups and other Committees that the Network needs to support its research objectives. The Operations Center is responsible for the preparation and maintenance of SOPs that cover all aspects of AMC activities and for assistance in development of Evaluation Criteria for Domestic and International Clinical Trials Sites, Protocol Chairs, the Group Chair, Committee Chairs, the Operations Center, and the AMC as a whole.
  • Clinical Trial Protocol Development: It is the responsibility of the AMC to develop the details of the research design, including definition of objectives and approaches, planning, implementation, analysis, and publication of results, interpretations, and conclusions of studies. The Operations Center is responsible, in accordance with the AMC standard operating procedures, for the preparation and implementation of procedures for development and submission of Network protocols to the CTEP Protocol and Information Office (PIO) in a timely fashion for review and approval by NCI.
  • ·      Clinical trials protocols should be developed, submitted, and implemented in accordance with the NCI “Investigator's Handbook" (http://ctep.cancer.gov/investigatorResources/docs/hndbk.pdf).
  • ·      AMC protocols should be preceded by a written Letter of Intent (LOI) from the AMC to the CTEP LOI Coordinator declaring interest in conducting a particular study. LOIs should be submitted using the LOI template at (http://ctep.cancer.gov/protocolDevelopment/lois_concepts.htm) to pio@ctep.nci.nih.gov.
  • ·      The Operations Center is responsible for communicating the results of the CTEP Protocol Review Committee to relevant Network Committees and Network members.
  • ·      All protocols utilizing NCI-sponsored investigational agents shall be conducted in accordance with the terms of the “Intellectual Property Option to Collaborators” (http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm) and the NCI Standard Protocol Language for Cooperative Research and Development Agreements (CRADAs) and Clinical Trial Agreements (CTAs). When new avenues of cancer therapy involving investigational agents are pursued, the clinical information should be acceptable to the U.S. Food and Drug Administration (FDA) for inclusion in a new drug application (NDA).
  • ·      The Network’s SOPs should include timelines for the steps involved in the development of LOIs, Concept Proposals, and protocols, and should include mechanisms for monitoring the performance of the Operations Center, Biostatistician and Network members in meeting these time lines. They should also include corrective action plans outlining the steps to be taken when these time lines are not met. Data concerning the AMC performance in meeting timelines for protocol development should be provided in the Annual Progress Report.
  • Study Monitoring (http://ctep.info.nih.gov/monitoring/section2.html#2.2.2): The Network is responsible for assuring accurate and timely knowledge of the progress of each study, and therefore must have 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, Phase II studies. Standard procedures include (but are not necessarily limited to):
  • ·      Precise tracking of patient accrual (eligible and ineligible patients) and adherence to protocol-defined accrual goals. In the event that the AMC wishes to continue accrual to a study beyond the protocol-specified total accrual goal for eligible and ineligible patients, the AMC must seek approval from CTEP prior to continuing patient accrual;
  • ·      Procedures for assigning dose level (for Phase I/dose escalation studies) at the time a new patient is entered, and assuring that the required observation period has elapsed before beginning a higher dose level;
  • ·      Ongoing assessment of patient eligibility and evaluability;
  • ·      Adequate measures to ensure timely medical review and assessment of individual patient data;
  • ·      Adequate measures to ensure timely submission of study data. These measures should include procedures for monitoring compliance with AMC guidelines for data timeliness on an institution and a study basis, including summary reports of data submission timeliness to be used for Institutional Performance Review and to be used for study monitoring (e.g., by the DSMC). These summary reports should also be included in the Annual Progress Report;
  • ·      Rapid reporting of treatment-related morbidity information and measures to ensure communication of this information to all relevant parties;
  • ·      Interim evaluation of outcome measures and patient safety information;
  • ·       Preparation of study monitoring reports describing patient accrual and demographics, data timeliness, toxicity, and other items as appropriate. Examples of study monitoring reports include reports prepared for study chairs, the biannual reports for AMC meeting agendas, and reports for Data and Safety Monitoring Committees; and
  • ·      Adequate policies and procedures for closure of studies. If the AMC wishes to close accrual to a study prior to meeting the initially established accrual goal, the interim results and other documentation should be made available to NCI staff for review and concurrence prior to implementation of the decision. It is recommended that statistical guidelines for early closure be presented as explicitly as possible in the protocol in order to facilitate these decisions. In the event that the DSMC has recommended early closure, DSMC procedures regarding notification of CTEP must be followed.
  • Data Management Policies and Practices: The responsibilities of the Operations Center for data management related to study monitoring include:
  • ·      Providing for central storage, security, processing and retrieval of study results;
  • ·      Incorporating security features consistent with DHHS guidelines;
  • ·      Implementing procedures for backing up the AMC clinical and administrative data, including intermittent duplication of the database with storage at a remote facility;
  • ·      Protecting patient confidentiality at all steps in the submission and analysis of clinical trials data and ensuring the technical integrity and security of the data management systems; and
  • ·      Providing NCI in a timely manner, upon the request of the NCI Grants Management Officer, true copies of data files and supporting documentation for all NCI-supported protocols that have a major impact on patterns of care, as determined by the NCI.
  • Quality Control of AMC Clinical Trials: Quality Control (QC) and Quality Assurance (QA) Programs are inherently linked. The Clinical Trials Monitoring Branch of CTEP provides direct oversight of NCI-sponsored clinical trial Consortia, including the AMC, QA/QC programs. The AMC is responsible for establishing and implementing mechanisms to assure the accuracy and reliability of its clinical trials data. Quality control is a complex topic spanning the entire range of diagnostic and therapeutic modalities employed by the AMC. Key items that should be addressed concerning quality control procedures include:
  • On-site Auditing: As a sponsor for investigational agents and the funding agency for other cancer clinical trials, FDA regulations require the NCI to maintain a monitoring program. The Clinical Trials Monitoring Branch (CTMB) of CTEP provides direct oversight of AMC's monitoring program. The AMC is responsible for maintaining its on-site auditing program in compliance with the Clinical Trials Monitoring Branch (http://ctep.cancer.gov/branches/ctmb/clinicalTrials/monitoring_multicenter.htm), and for submitting the results of audits to the NCI in accordance with the guidelines. The on-site audit will address issues of data verification, protocol compliance, compliance with regulatory requirements for the protection of human subjects, and investigational agent accountability.
  • ·      On-site auditing of AMC Clinical Trial Site institutions should be planned to occur at least twice during the project period.
  • ·      Any serious problems with data verification or compliance with Federal regulations must be reported to the Clinical Trials Monitoring Branch immediately.
  • ·      In the event that the NCI determines that an AMC Clinical Trial Site Institution failed to comply with these guidelines, the accrual of new patients to AMC protocols at the affected institution shall be suspended immediately upon notice of the NCI determination. The suspension will remain in effect until the AMC conducts the required audit and the audit report or remedial action is accepted by the NCI.
  • ·      The Operations Center will be responsible for notifying any affected participating institution of the suspension. During the suspension period, no funds from this award may be provided to the participating institution for new accruals, and no charges to the award for new accruals will be permitted.
  • Data Report to CTEP: The Consortium will be responsible for assuring accurate and timely monitoring of the progress of each study, and therefore must have standard procedures for timely data collection and data management.  Standard procedures include (but are not necessarily limited to):
  • ·      Adequate measures to ensure timely submission of clinical trials data (e.g., adverse events, anticancer response, etc.) from Member Institutions to the AMC Data Management Center.  These measures should include procedures for monitoring compliance with Consortium’s guidelines for data timeliness on an institution and a study basis, including summary reports of data submission timeliness to be used for Institutional Performance Review and to be used for study monitoring (e.g., as specified by the Data and Safety Monitoring Plan)].
  • ·      Rapid reporting of treatment-related morbidity information and measures to ensure communication of this information to all relevant parties.  For investigational agents sponsored by the NCI, this involves reporting to the Investigational Drug Branch (IDB), CTEP, via the expedited CTEP-Adverse Event Reporting System (AERS) according to CTEP guidelines specified in each protocol (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adverse_events.htm)
  • ·      Preparation of study monitoring reports describing patient accrual and demographics, data timeliness, toxicity, and other items as appropriate.  Examples of study monitoring reports include reports prepared for study chairs, the semiannual reports for Consortium meeting agendas, and reports as required to comply with the Consortium’s Data and Safety Monitoring Plan; and
  • ·      Adequate policies and procedures for closure of studies.  If the Consortium wishes to close accrual to a study prior to meeting the initially established accrual goal, the interim results and other documentation should be made available to NCI staff for review and concurrence prior to implementation of the decision.  It is recommended that statistical guidelines for early closure be presented as explicitly as possible in the clinical trial protocol in order to facilitate these decisions.  In the event that the study is recommended for early closure for safety reasons, procedures in the Data and Safety Monitoring Plan regarding notification of CTEP must be followed.
  • Publications: Timely publication of major findings is central to the mission of the AMC and is a primary means by which the AMC’s accomplishments can be evaluated.
  • ·      Publication or oral presentation of work done via the AMC’s Cooperative Agreement requires appropriate acknowledgment of NCI support.
  • ·      For publications using an agent supplied under a CRADA or CTA, the NCI pharmaceutical collaborator will have 30-day review as per the NCI Standard Protocol Language for CRADAs and CTAs.
  • ·      For Consortium publications associated with NCI-support that do not involve agent(s) supplied under CTEP Collaborative Agreements (except as noted below for press releases), the AMC Program Director must receive a copy of the manuscript 30 days in advance of publication and a copy of abstracts should be provided three days in advance of publication. Unlike the situation for agent(s) supplied under CTEP Collaborative Agreements, however, no review or comments will be provided by CTEP and/or OHAM unless specifically requested by the Consortium. This is simply a confidential notification.  Review timing for publications other than abstracts or manuscripts should be discussed with appropriate NCI/OHAM staff.
  • ·      All press releases issued by the NCI and/or the Consortium on primary study findings and results require review by NCI, NIH, and DHHS.  Pre-review timing for press releases on study finding and results must be discussed with and approved by the AMC Program Director. The AMC is encouraged to send drafts of press releases on other topics to NCI for pre-review and/or pre-release notice.
  • AMC Meetings: The Operations Center is responsible for the organization of biannual meetings to review the Network’s progress, establish priorities, and plan future activities. Additional regional meetings between AMC members and meetings with NCI staff may be held as needed. Relevant responsibilities for meeting organization include:
  • ·      Arranging for appropriate meeting space and accommodations for attendees;
  • ·      Developing and distributing meeting agendas;
  • ·      Providing the Report of Studies (including the ANCHOR trial) to include information detailing patient accrual and demographics, data timeliness, toxicity experienced by study participants, and other items as appropriate, including outcome data as appropriate. The Operations Center is responsible for assuring that copies of the Report (electronic and/or hard copy) are distributed to AMC members and NCI program staff; and
  • ·      Preparing summaries as appropriate after each meeting to be sent to AMC members and NCI program staff.
  • AMC Communications: The Operations Center is responsible for establishing routine electronic communication with Clinical Trials Site Institutions to facilitate protocol development and study monitoring and to facilitate the work of the AMC’s Study and Scientific Committees. Relevant communication methods include web site postings, e-mail, teleconferences, and video conferences.
  • Compliance with Federal Regulations Concerning Clinical Research: The Operations Center is responsible for assuring that the Network is in compliance with all applicable federal regulations concerning the conduct of human subject research. Policies and guidelines to be addressed include:
  • ·      OHRP Assurances: The AMC must assure that each member has a current, approved Federal wide Assurance (FWA), on file with OHRP. Information on assurances is available on the OHRP website at: http://www.hhs.gov/ohrp/.  In addition, federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained.
  • ·      Ensuring that all U.S. member sites are members of the NCI CIRBs and use the NCI CIRB for all AMC multi-site clinical trials and eligible related studies. 
  • ·      IRB Review of International AMC Protocols: The Central Operations Office must assure that each AMC clinical trial protocol is reviewed and approved by each foreign member institution’s IRB prior to patient trial entry, and must ensure that each clinical trial protocol undergoes continuing review no less than once per year by the IRB so long as the clinical trial is active.
  • ·      Assuring Appropriate Informed Consent: The AMC must have procedures in place to ensure that each member institution is trained and understands the policies and procedures relevant to ensuring that patients are enrolled on studies with appropriate informed consent per NCI/NIH policy and federal regulations.
  • ·      Institutional Review Board (IRB) Review of the Clinical Research Program and Statistics and Data component: (http://archive.hhs.gov/ohrp/humansubjects/guidance/engage08.html): An IRB should review and approve the research activities related to the receipt and processing of the identifiable private information by the Clinical Research Program and Statistics and Data component for ongoing domestic clinical trials and clinical trials conducted in foreign institutions. The IRB should ensure that there are sufficient mechanisms in place to adequately protect the privacy of subjects and maintain the confidentiality of the data.
  • ·      Education on the Protection of Human Subjects: NIH policy requires education on the protection of human subject for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. This policy is available on the NIH website at: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
  • Managing and coordinating the acquisition and shipping of protocol specified tumor specimens and biological fluids (with relevant clinical data) to the appropriate laboratories for testing and to a tumor/specimen repository for storage of specimens for future correlative laboratory studies. Any tumor and tissue repository must be in compliance with OHRP regulatory requirements for such repositories (http://ohrp.osophs.dhhs.gov/humansubjects/guidance/reposit.htm).
  • Fiscal management of the Network, including:
  • ·      Funds for Training, International Studies and Community Representatives will be dispersed in accordance with the AMC By-Laws and by direction of the Group Chair and approval NCI Project Officer.
  • ·      Distribution of funds from the Patient Recruitment and Retention to Clinical Trial Site Institutions to support special clinical research costs for patients accrued onto Network clinical trials. Funds will be disbursed on a capitation basis upon documentation of accrual. It is anticipated that for each Network protocol, the capitation formula for institutional reimbursement required to offset specific research expenses will be reviewed and approved by the Executive Committee.
  • ·      Allocation, distribution and per capita patient reimbursement plans and major expenditures for the ANCHOR trial recommended by the ANCHOR Trial Coordinating Committee (ATCC) will have to be approved by the AMC EC prior to implementation.
  • Progress Report: Submission of annual progress reports to the NCI that describe activities and accomplishments during the previous year of funding. The report should include:
  • ·      A summary of the overall performance of the Operations in meeting its responsibilities to the AMC for protocol development, study monitoring, and complying with Federal regulations.
  • ·      Summary data on performance of each AMC Clinical Trials Site, including protocol accrual, quality and timeliness of submitted data, and involvement in protocol development activities.
  • ·      Research plan, changes in procedures and/or staff, and the proposed budget for the coming year.
  • Patient accrual and credit: The AMC is expected to accrue at least 120 domestic patients (U.S.) per year and 80 patients per year in international resource limited settings. A patient entered on an interventional protocol (treatment, vaccine, etc.) is counted as one patient, as is one entered for pharmacokinetic studies. Patients entered on non-treatment trials such as natural history studies where patients are followed for more than six months will also count as one patient credit. Such patients cannot simultaneously count towards two trials if on natural history studies. All other non-treatment protocols including those involving a single tissue and/or body fluid collection will be counted as half a patient credit.
  • Specimen Banking: The AMC will use the AIDS and Cancer Specimen Resource (ACSR) as the central resource for the storage of tumor specimens and biological fluids from patients entered onto Network clinical trials for future correlative studies. The ACSR is currently funded as a separate cooperative agreement with the NCI (http://acsr.ucsf.edu).
  • The release and utilization of tumor specimens and biological fluids, banked from the ANCHOR trial, to AMC investigators or to out of network investigators will require prior approval by OHAM/NCI.
  • Protocol Implementation Fund (PIF): The AMC will maintain a restricted portion (approximately $1,600,000 in year 1) of the AMC award to support efforts related to patient accrual and retention costs for patients accrued onto AMC clinical trials (excluding the ANCHOR trial). The funds will be allocated according to the instructions of the EC and disbursed on a capitation basis after documentation of patient accrual. A primary anticipated use of these funds is to provide incentive to Clinical Trial Sites for increased accrual above the minimum requirement to maintain Clinical Trial Site status. The PIF will also cover: protocol-mandated drug purchases, storage, and distribution for international trials; costs for laboratory diagnostics not reimbursed as standard of care; clinical trial insurance; computerized tomography (CT) scans; remote audits of radiotherapy machine output and on-site dosimetry review audits for international trials.  These funds will be restricted for this purpose only and cannot be used for other purposes without permission from the AMC Program Director. This restriction will be incorporated into Terms of Award in the Notice of Grant Award.
  • Member Clinical Trial Site Institutions: The AMC is responsible for having a comprehensive and consolidated membership roster of all its sites and associated investigators and research staff and for maintaining the roster for both auditing and financial management purposes with “real-time” status of all members. All member institutions/sites must have appropriate and accurate NCI institutional codes approved by NCI. All sites will participate in on-site Monitoring Program established by the AMC and will follow AMC’s SOPs for the conduct of clinical research and complying with the AMC’s By-Laws.
  • Human Subjects Protection: Each institution must comply with OHRP and FDA regulations concerning protection of human subjects. Core Site Institutions must implement the procedures established by the AMC to meet OHRP and FDA requirements for the protection of human subjects.
  • Adverse Event Reporting: All AMC member Institutions will follow the procedures established by the AMC for assuring timely reporting of all serious and/or unexpected adverse events.
  • Investigational agent responsibilities: Member institutions will  implement the procedures established by the AMC for assuring that AMC investigators performing trials involving NCI Investigational Agents are NCI registered investigators (Form 1572) and for assuring that the AMC is in compliance with CTEP requirements described in the NCI Investigators' Handbook for storage and accounting for investigational agents (including NCI/HHS Drug Accountability Records (DAR) procedures), and is in compliance with FDA requirements for investigational agents.
  • International Clinical Trial Sites: An International Clinical Trial Site will be directed by a Lead Senior Collaborator from the Foreign Institution. A Foreign Site may have a U.S. Collaborator from the AMC as a consultant for that Site. The AMC U.S. Collaborator may have at least 5 percent effort if he/she is the Chair of a Foreign Clinical Trial Protocol for the duration of the protocol. The Sites are expected to meet the minimal requirements of Foreign Clinical Site criteria defined by the AMC for a Foreign Clinical Trial Site. The sites will be reimbursed for per capita patient accrual. The AMC will conduct an annual performance evaluation of the Sites and will develop correction plans for underperforming Sites who may be subject to termination.
  • Network Resource Laboratory: The network laboratory will be responsible for performing standard testing of the correlative science pertaining to clinical trials and preclinical drug screening functions. This laboratory will have the necessary Cores such as the Pathology Core (Hematopathology, dermatopathology, etc.), Virology Core (HPV, EBV, KSHV), Pharmacology Core (clinical pharmacology and pharmacodynamics), and a Biomarker Core (gene expression, cytokine measurement in tissues and blood and body fluids). The network resource laboratory will use standard good laboratory practice techniques and will maintain a quality assurance/quality control program that will insure the integrity of the data generated.
  • If the PD/PI serving as AMC Group Chair is been replaced by another individual as AMC Chair in a procedural vote by the AMC Steering Committee, the Institution of PD/PI named in the notice of grant award who no longer serves as AMC Chair will release the award to the Institution of the new AMC Chair upon NCI approval.
  • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

One or two designated NCI Program Directors acting as the Project Scientist/Coordinator(s) will have substantial involvement in the AMC program to a degree that is above and beyond the normal programmatic stewardship responsibilities in the administration of grants. This individual(s) will be the main NCI contact with the awardees for scientific and/or analytic issues.

As needed, additional NCI scientific staff members with relevant expertise may also have substantial involvement (e.g., as Collaborators) in the conduct of the AMC scientific activities.

All NCI staff members who may be substantially involved in the scientific activities of AMC will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

The NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Main NCI responsibilities include:

  • Interacting with the PD(s)/PI(s) on a regular basis to monitor study progress (which may include: regular communications with the PD(s)/PI(s) and staff, periodic site visits for discussions with awardee research teams, observation of field data collection and management techniques, quality control, fiscal review, etc., as well as attendance at Steering Committee, Data and Safety Monitoring Committee, and related meetings);
  • Serving as voting members of the Executive Committee, the Scientific Planning Committee and, if applicable, subcommittees;
  • Assisting in the design and coordination of research activities for awardees;
  • Coordinating clearances for investigational agents held by NCI (the NCI may reserve the right to cross file or independently file an Investigational New Drug Application form with the FDA);
  • Contributing scientifically to the process of data collection and participating in data analyses and publication efforts of the Consortium;
  • Advising on the management and technical performance of the AMC investigations;
  • Coordinating activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocols and statistical evaluation of data; in the preparation of questionnaires and other data recording forms;
  • Assisting in the publication of results;
  • Reviewing and approving clinical trial protocols to ensure that they are within the scope of peer review and are safe, as required by Federal regulations (final drafts of protocols approved by the Executive Committee will be reviewed by the CTEP Protocol Review Committee);
  • Monitoring protocol progress and involvement in protocol closure. The NCI Program Director and NCI Scientific Coordinator will monitor protocol progress and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; and (f) emergence of new information that diminishes the scientific importance of the study question. The NCI will not permit further expenditures of NCI funds for a study after requesting closure (except for patients already on-study);
  • Reviewing and providing advice regarding the establishment of mechanisms for quality control and study monitoring. For specific Phase I/II trials with NCI-sponsored agents, the NCI will arrange for the Clinical Trial Monitoring System, CTMS, to document regulatory compliance, to maintain a computerized data base, and to produce periodic routine reports of the results and special reports as necessary. For Phase II trials with NCI-sponsored investigational agents not requiring the above described monitoring, NCI will delegate to the AMC the task of providing an independent audit of each research study. The CTMS shall be used to conduct these audits. Random audits by NCI staff will be performed to assure that the awardee is performing the delegated audit duties; and
  • Making recommendations to the EC and the SPC on the allocation of monies from the Discretionary Fund.

The NCI reserves the right to adjust funding, withhold, suspend, or terminate the AMC award for poor performance and/or non-adherence to the terms and condition of the award.

Areas of Joint Responsibility include:

Execution of this program will require collaboration among NCI staff, the Group Chair, the Directors of the Clinical Trials Sites, the Principal Investigator of the Operations Center, the Group or Protocol statistician, the Chair of the Network Laboratory, and other NIH-Funded Clinical Trials Networks. The NCI Program Director will assist in coordinating the activities of the AMC with the other Networks as defined below and will facilitate the exchange of information. Specific tasks and responsibilities in carrying out the activity will be shared among the awardee and NCI staff. NCI reserves the right of final authority to approve all tasks performed in the context of this award.

NCI Staff members and Awardees shall share responsibility for the following activities:

  • Executive Committee: The leadership of the AMC will be vested in the Executive Committee, which will perform the executive and final scientific review functions of the AMC. Its membership will consist of the Group Chair, the Group Vice Chair, a senior representative of the Network Laboratories, the Director of the Operations Center, the Group Statistician, the NCI Program Director and Scientific Director (with one vote between these two NCI representatives) and a community representative. The Executive Committee will be responsible for the establishment and amendments and final approval of the AMC’s bylaws and standard operating procedures, review and approval of new protocols for implementation, Clinical Trials Sites' performance evaluation, approval of new member sites (including ANCHOR trial implementation sites) and cooperative group collaborations, approval of funds from the discretionary, protocol implementation fund and Clinical trial research fund and final approval of budgets including ANCHOR.
  • Strategic Planning Committee (SPC): The committee that is primarily responsible for the research direction of the Network and for assuring that the clinical research procedures of the Network are being followed and sufficient to meet these objectives and protect participants enrolled on AMC clinical trials. Its membership will be prescribed by the Network By-Laws and should include (but need not be limited to) the AMC Chair, Working Group Chairs, the Operations Center Director, the Group Biostatistician, domestic Clinical Trial Site representation, international Clinical Trial Site representation, and patient/family representatives. Each full member will have one vote, with the exception for NCI representatives, who will jointly have one vote. Awardee members of the SPC will be required to accept and implement policies approved by the SPC.
  • International Resource Committee: The Working Group responsible for facilitating selection, vetting and accreditation and capacity building of Foreign Clinical Trials Sites. The committee will be responsible for working out the logistics for conduct of clinical trials in international sites. Capacity building will include training for good clinical practices, good laboratory practices, personnel training for clinical management and data collection.
  • ANCHOR Trial Coordinating Committee (ATCC): The leadership of the ANCHOR trial will be vested in the ATCC. Its membership will consist of the AMC Chair, ANCHOR trial protocol Chair and Vice Chair, a senior representative of the Network Laboratories, the Director of the Operations Center, the Group Statistician, the NCI Program Director and Scientific Director (with one vote between these two NCI representatives) and a community representative. The ATCC will be responsible for the establishment and amendments and the ANCHOR trial initial site selection, new member sites and performance evaluation, develop a budget plan for the ANCHOR trial, make recommendations to the AMC EC for ANCHOR trial expenditures from the ANCHOR budget set by the NCI.
  • Data and Safety Monitoring Committee and Ad Hoc Monitoring Committees: The major emphasis of the Network is on exploratory Phase I and Phase II trials. However, the AMC has the capability to expand to Phase III trials. Phase III trials will require an independent Data and Safety Monitoring Committee (DSMC) established by the Executive Committee; the DSMC is responsible for insuring the safety of participants for each AMC clinical trial, the validity of data, and the appropriate termination of studies for which significant benefits or risks have been uncovered or when it appears that the trial cannot be concluded successfully. The Data and Safety Monitoring Committee will review interim results periodically and report to the EC Committee and the NCI. The NCI Scientific Coordinator, or his designee, will serve as an advisory (non-voting) member of the DSMC.
  • In all other studies, exploratory Phase I and Phase II trials, where warranted, the NCI Program Director and NCI Scientific Coordinator will facilitate, and the awardee shall allow for, interim data and safety monitoring through ad hoc committees established by the Operations Center in accordance with the Data and Safety Monitoring Plan for early phase studies.
  • Additionally, an agency program official or NCI Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

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 Steering 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 DHHS regulation 45 CFR Part 16.

3. Reporting

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.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, 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 instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (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: support@grants.gov

Scientific/Research Contact(s)

Mostafa Nokta, M.D., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3366
Email: Noktam@mail.nih.gov

Peer Review Contact(s)

Referral Officer
National Cancer Institute
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Financial/Grants Management Contact(s)

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.


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