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

The Experimental Therapeutics Clinical Trials Network (ETCTN) Pharmacokinetic Resource Laboratories (U24 Clinical Trial Not Allowed)

Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

New

Related Notices
  • January 17, 2019 - Notice of a Pre-Application Webinar for RFA-CA-19-007 and RFA-CA-19-008. See Notice NOT-CA-19-021.
Funding Opportunity Announcement (FOA) Number

RFA-CA-19-008

Companion Funding Opportunity

RFA-CA-19-007, UM1 Research Project with Complex Structure Cooperative Agreement

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)

 93.395

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) issued by The National Cancer Institute (NCI) is to create Pharmacokinetics Resource Laboratories (PK Laboratories) that will support the Experimental Therapeutics Clinical Trials Network (ETCTN). The PK Laboratories will be expected to organize specimen collection and subsequent analysis of pharmacokinetic endpoints, drug-drug interactions, cytochromes P450 (CYP) interactions, and food effects in ETCTN studies of NCI Investigational New Drug (IND) agents. The overarching goal of the ETCTN PK Laboratories is to advance the clinical development of NCI-IND agents through achieving comprehensive understanding of pharmacokinetic behavior of these agents studied in ETCTN protocols. The ETCTN Pharmacokinetic Resource Laboratories will assure the availability of physicians, clinical pharmacologists, nurses and scientists who have the appropriate expertise in pharmacokinetic studies for early drug development and translational research. This FOA seeks U24 cooperative agreement applications from multidisciplinary groups that will conduct all pharmacokinetic studies for ETCTN early phase clinical trials filed to the IND applications in NCI’s Division of Cancer Treatment and Diagnosis (DCTD), Cancer Therapy Evaluation Program (CTEP). 

Key Dates

 

Posted Date

January 10, 2019

Open Date (Earliest Submission Date)

April 22, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

May 22, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on  this date. 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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October-November 2019

Advisory Council Review

 January 2020

Earliest Start Date

April 1, 2020

Expiration Date

May 23, 2019

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 this Funding Opportunity Announcement (FOA) is to create two Experimental Therapeutics Clinical Trials Network (ETCTN) Pharmacokinetics Resource Laboratories (PK Laboratories) as an infrastructure to support the ETCTN Clinical Sites. PK Laboratories will be responsible for the organization of specimen collection and subsequent analyses of pharmacokinetic endpoints, drug-drug interactions, cytochromes P450 (CYP) interactions, and food effects in ETCTN studies of NCI Investigational New Drug (IND) agents. The ETCTN PK Laboratories will conduct all pharmacokinetic studies for ETCTN clinical trials involving NCI-IND agents in NCI’s Division of Cancer Treatment and Diagnosis (DCTD), CTEP, NCI (http://ctep.cancer.gov). Clinical trials conducted by the ETCTN provide the dose, schedule, and early evidence of therapeutic activity including "proof of concept", "proof of mechanism", and target engagement/inhibition.

    ETCTN Objectives include:

    The research objective of the ETCTN is for the early-stage clinical development of novel cancer treatments that include NCI-IND agents based on sound preclinical findings, and that are consistent with national priorities for developmental therapeutics clinical cancer research. To meet this objective, all ETCTN awardees jointly will be expected to:

    • Use a coordinated and collaborative integrated team science approach in the drug development process.
    • Acquire high quality human specimens for ETCTN correlative laboratory studies.
    • Integrate scientific rigor into biomarker development and clinical trials.
    • Provide efficient and timely activation and conduct of clinical trials that meet regulatory requirements and Good Clinical Practice (GCP) standards and principles.
    • Promote collaborations with cancer biology experts to investigate critical pathways and processes in the treatment of oncology patients with investigational drugs.
    • Provide clinical study leadership opportunities for early career clinical investigators.
    • Commit to enrollment of racial/ethnic and rural populations to decrease cancer disparities.

    Key Terms for this FOA:

    Terms related to the organization of ETCTN:

    • ETCTN: The Experimental Therapeutics Clinical Trials Network, the network of sites and infrastructure that is devoted to the early clinical development of anticancer drugs for which NCI/CTEP is the Investigational New Drug (IND) holder.
    • ETCTN site: the institution that is the recipient of the ETCTN UM1 award under the companion UM1 RFA-CA-19-007 (also referred to as Lead Academic Organization, LAO) plus any clinical entities collaborating with the LAO (also referred to an Affiliated Organizations, AOs).
    • Cancer Therapy Evaluation Program (CTEP), which is responsible for NCI clinical trials.

    Other terms related to the ETCTN

    • Biomarker: A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition.
    • Pharmacokinetics (PK): study of drug absorption, distribution, metabolism, and excretion.
    Background

    The purpose of the ETCTN is to develop novel NCI-IND anticancer agents and to capitalize on NCI resources and molecularly characterized tumors to find appropriate biomarkers to select patients most likely to respond to specific agents. ETCTN clinical studies determine the safety of NCI IND agent drug combinations, find early signals of clinical activity of these agents in targeted populations, and perform in-depth analysis of biomarkers of response and resistance. CTEP currently holds approximately 100 INDs for investigational oncology agents which involve 60 pharmaceutical/biotechnology collaborators. Agents under evaluation include small molecules, immune-oncology agents, antibodies, vaccines, targeted toxins, oligonucleotides, and gene transfer agents.

    Pharmacokinetics determinations (with appropriate validation and interpretation) include pharmacokinetic measures of agent absorption (A), distribution (D), metabolism (M), and excretion (E). Commonly determined parameters are: area under the curve (AUC), maximum agent concentration (Cmax), clearance (CL), half-life, volume of distribution, and others. Drugs may be eliminated in the unchanged (parent) form or undergo metabolism to one or more active and/or inactive forms. The overall set of processes monitored (often referred to as ADME) ultimately determines systemic exposure to a drug and its metabolites after drug administration. This systemic exposure, reflected in plasma drug or metabolite, concentrations, or both, is generally correlated with both beneficial and adverse drug effects. All drugs and biologics show inter- and intra-individual variability in PK measures and parameters. (See FDA clinical pharmacology guidance: https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm064982.htm)

    NCI Organizational Groups Involved in the ETCTN

    Several NCI organizational groups (branches/programs/services) will have defined roles to achieve the research goals of the ETCTN. The ETCTN PK Laboratories will be expected to interact as appropriate with such NCI branches/programs/services as: CTEP; Biometric Research Branch (BRB); Cancer Diagnosis Program (CDP); Cancer Trials Support Unit (CTSU); Central Institutional Review Board (CIB); Clinical  Data Management System (CDMS); Clinical Trials Branch in the Cancer Imaging Program( CIP); Clinical Trials Monitoring Service (CTMS); Oncology Patient Enrollment Network; and Regulatory Support Service.

    Research Objectives and Main Requirements of this FOA

    The ETCTN PK Laboratory awards will provide the major resource for rapid, efficient, systematic evaluation and determination of the ADME profiles in patients participating in early phase clinical trials. The ETCTN PK Laboratories will be responsible for establishing pharmacokinetic profiles of NCI-IND anticancer agents and their metabolites in blood. Specific agents (alone and in combinations) will be analyzed for their half-lives and rates of elimination for these investigational agents to ensure the safe and effective therapeutic management of drugs in an individual patient. The ETCTN PK Laboratories will provide:

    • Technical and clinical evaluation of assays for study drug(s) PK that are quality assured/quality controlled and standardized for use in plasma and/or tumor tissue;
    • Evaluation of drug-drug interaction risk for each drug and its active metabolites in relationship to other therapeutics and concomitant medications;
    • Definition of PK sampling strategies, limited sampling strategies and population PK;
    • Evaluation of PK in plasma and tissue; and
    • Timely reporting and analysis to the study team and to NCI of the results of PK analyses.

    Specific Research Capabilities and Requirements

    ETCTN, including the ETCTN PK Laboratories, investigators and personnel will collaborate with each other and with involved NCI staff members to achieve ETCTN goals, objectives, and capabilities.

    Applicants proposing ETCTN PK Laboratories will be expected to:

    • Have in place prior to award an infrastructure to support PK studies for ETCTN clinical trials from trial initiation through clinical development of NCI-IND agents;
    • Provide access to multidisciplinary clinical and pharmacology experts, and
    • Perform biostatistical/computational data analysis, interpretation, and compartment modeling for PK studies.
    • Prospective applicants must have extensive experience in PK studies for early phase clinical trials and have the following specific capabilities:
    • Performing PK analysis in high quality specimens in the context of clinical trials;
    • Established Standard Operating Procedures (SOPs) for data quality and laboratory quality control, including institute quality control for reagents and technologies for ETCTN PK studies;
    • Conducting PK studies according to Good Laboratory Practice (GLP) principles;
    • Providing preliminary data to inform the design and conduct of PK studies for investigational drugs;
    • Evaluating PK data from early phase experimental therapeutic clinical trials using single or combinations of novel NCI CTEP IND agents;
    • Serving as PK resource centers within the ETCTN for collaborative validation studies, statistical and computational analyses, data management, and coordination of ETCTN pharmacokinetic studies; and
    • Providing technical and scientific expertise to CTEP Project Teams related to PK activities in the drug development plan.

    Additional NCI Support for the ETCTN sites. Through separate contracts, the NCI/DCTD/CTEP will provide the awardees with standardized central operational, regulatory, and administrative support (for details, go to: https://ctep.cancer.gov/initiativesPrograms/etctn_infrastructure.htm.)

    Key Capabilities and Attributes of Required Components

    Applicants responding to this FOA should have appropriate capabilities and attributes related to PK studies. Awardees will be expected to interact with other ETCTN sites and consortia, as well as relevant external programs.

    Scientific Leadership

    The PDs/PIs of the PK Laboratory will be responsible for studies that evaluate drug absorption, distribution, metabolism and excretion and, as appropriate, studies to evaluate proof of mechanism and suitable patient candidates. The goals of this FOA require the U24 scientific leadership to have a well-defined plan for communications and collaborations UM1 awardees and their participating clinical sites.

    Pharmacokinetic Laboratory

    Each applicant must have the capability to support clinical trials by conducting various pharmacokinetic laboratory assays of clinical specimens. The proposed investigators should therefore demonstrate the availability of state-of-the art analytical laboratory equipment to support the goals of the award. The laboratory will require highly trained laboratory personnel experienced in the pharmacokinetic analysis of clinical specimens, and a biostatistician who will help design specimen acquisition and data analysis.

    Coordination of Specimen Collection, Tracking, and Associated PK Laboratory Activities

    The applicant must have the ability to accept and transfer specimens from clinical trials both nationally and internationally. This component will be responsible for all administrative duties related to specimen collection and tracking and will reside at the contact PD/PI’s institution.

    Team Science for Project Development

    Each awardee will be expected to participate in multi-disciplinary, agent specific scientific Project Teams to provide expertise in the development of PK studies.

    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

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NIH intends to commit $750,000 (total funds) in FY 2020 to fund up to 2 awards.

    Award Budget

    Application budget requests are limited to $320,000 (direct costs) per year.

    Award Project Period

    Project period of 6 years should be requested. 

    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

    Higher Education Institutions

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

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

    o   Hispanic-serving Institutions

    o   Historically Black Colleges and Universities (HBCUs)

    o   Tribally Controlled Colleges and Universities (TCCUs)

    o   Alaska Native and Native Hawaiian Serving Institutions

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

    Nonprofits Other Than Institutions of Higher Education

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

    For-Profit Organizations

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

    Governments

    • State Governments
    • County Governments
    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 not 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.
    • o   NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
    • eRA Commons - Applicants must have an active DUNS number 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.

     Individual(s) designated as Program Director(s)/Principal Investigator(s) (PDs/PIs) are expected to be national and international leaders in cancer-related pharmacokinetic studies for early phase clinical trials of novel therapeutic agents and translational research.

    Proposed investigators must be highly capable of inter- and trans-disciplinary team-based research with investigators involved in the design and conduct of clinical trials.

    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:

    S. Percy Ivy, M.D.

    National Cancer Institute (NCI)

    Telephone: (240) 276-6107

    Email: ivyp@ctep.nci.nih.gov

    Page Limitations

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

    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.  

    SF424(R&R) Other Project Information

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

    Facilities & Other Resources: Provide a succinct description of the pharmacokinetic related resources, infrastructure and facilities that are available. Include information on resources, infrastructures that will be needed and used for the interactions with ETCTN Sites (e.g., information technology systems, logistical infrastructure, specimen receiving, and handling facilities, etc.).

    Describe the analytical equipment available for pharmacokinetic analyses and the experience of the technical staff who will be performing the analyses.

    The applicant should provide documentation regarding storage facilities and the ability to accept and transfer specimens from clinical trials both nationally and internationally.

    Other Attachments: Applicants must provide the following attachments identified in the Research Strategy. The filename provided must be used for each attachment, as it will become a bookmark in the application.

    Attachment 1. Communications Data (use filename Communications)

    – Outline existing weekly, monthly, quarterly, biannually ad hoc and annual meetings to monitor specimen collection and tracking, as well as PK study progress and results.

    Attachment 2. Organizational Charts (use filename Org Charts)

     – Outline of the organization of the proposed ETCTN PK Laboratory site(s).

    Attachment 3. Timelines (Use filename Timelines)

     – Existing timelines (based on past performance) should be provided and may include pharmacokinetic study completion and submission of abstracts and manuscripts.    

    Attachment 4. GLP Compliance (use filename GLP Compliance)

    - Provide a list of Standard Operating Procedures that the team has in place to demonstrate adherence to Good Laboratory Practice. (Do not provide the full procedure and policy documents.)  

    SF424(R&R) Senior/Key Person Profile

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

    The applicants must designate an appropriately qualified PD/PI who will be primarily responsible for PK Laboratory operations. PD(s)/PI(s) are expected to be recognized leaders in the areas of early phase PK drug and biologic development studies and have documented leadership experience.

    Each ETCTN Laboratory application should identify a statistician(s) with the skill and expertise in PK studies. Identify a senior statistician and other statisticians with expertise in early phase clinical trial pharmacokinetic studies.

    For each Senior/Key Person, document in their biosketches, as applicable, respective expertise and past performance in the conduct of PK determinations in the context of cancer clinical trials and clinical development of experimental therapeutics.

    R&R Budget

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

    The requested budget should not include costs for the standardized central operational, regulatory and administrative support provided by the NCI or existing NCI ETCTN Contractors. These services will be directly funded by the NCI at no cost to the applicant. See: https://ctep.cancer.gov/initiativesPrograms/etctn_infrastructure.htm

    Cost for data management on site may be included. However, a clear justification must be provided if such costs are related to the use of Medidata Rave as an interface to NCI-supported services (CTMS).

    In projecting cost, applicants should assume that each of the two ETCTN U24 awardees will be required to process/analyze approximately 15,000 PK specimens per year.

    The applicant can request less than the estimated amounts with appropriate budget justification.

    To justify the budget, the applicant needs to describe in detail (in the budget justification) the number of patient specimens expected for PK studies. For budget calculations, please note that each ETCTN LAO is expected to accrue at a minimum 100 patients to early phase clinical trials.

    Funds for travel. Two representatives from the ETCTN site (at least one of whom must be the PD/PI) will be required to travel to two NCI/CTEP Early Drug Development (EDD) meetings per year. Travel costs for two presenters for major national/international meetings should be included in the budget for Scientific Leadership.

    Senior/Key Person and Other Personnel. The budget request may include estimated costs of salary support (based on level-of-effort) for the PD(s)/PI(s), and other collaborators. 

    Each individual designated as a PD/PI must commit a minimum of 1.2 person-months of effort per year. This minimal effort level must be maintained throughout the entire project period.

    Pharmacokinetics, Specimen Collection, Tracking and Associated PK Activities. The request should include costs of research that are not considered a “cost of treatment” by medical insurers, and therefore are not reimbursed by insurers (e.g., blood and urine collection, etc.).

    The budget should include costs for the following activities:

    • Timely mailing/shipping or handling research-related patient specimens, forms, and materials.
    • Laboratory studies performed on specimens (e.g., blood, tumor tissue, buccal cells, plasma, serum, varied tissues, cerebrospinal fluid, pleural fluid, ascites fluid, hair, etc.) obtained from participants enrolled on ETCTN early phase clinical trials.

    Budgets shall NOT include or reflect any costs for the following activities:

    • Correlative studies and biomarker assays to enhance specific clinical trials; and
    • Any costs that are not solely research-related.
    R&R Subaward Budget

    All instructions in the SF424 (R&R) Application Guide must be followed. Budgets for affiliated consortium component organizations must be provided as subaward budget attachment forms

    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 Specific Aims for the proposed ETCTN PK Laboratory to perform comprehensive PK studies related to ETCTN clinical trials evaluating novel anticancer treatments. These Aims must be based on the demonstrated ability of the applicants to perform PK studies for at least 15,000 specimens per year.

    Research Strategy: The Research Strategy should consist of sub-sections A-D, as defined below:

    Sub-Section A: Overview of Relevant Capabilities and Past Performance

    Summarize the team ability and collective experiences in conduct of PK studies for early phase clinical trial experimental therapeutic agents. Describe relevant team accomplishments, infrastructure, capabilities. Specific information to provide must include (but is not limited to) the following aspects:

    Main Capabilities

    • ·    Analyzing PK data for clinical trials of experimental cancer therapeutics;
    • ·    Systematic approach to sample identification, tracking, processing and data sharing with study investigators; and
    • ·    Developing validated PK assays with control standards.

    Past Performance

    Address briefly the following aspects:

    • ·    Highlights of published results from clinical, translational and/or basic research; and
    • ·    Accomplishments of the team in performing early phase clinical trial related PK studies.

    Sub-Section B: Scientific Leadership

    Outline how the leadership of PK Laboratory will oversee the conduct of ETCTN pharmacokinetic studies and facilitate interactions with other ETCTN and NCI staff. Address, at a minimum, the following aspects:

    • The leadership and governance structure planned, including organization of the proposed site(s);
    • Integrating/coordinating activities related to the development and conduct of PK studies with other ETCTN participants and other NCI-sponsored research programs;
    • The institution’s willingness to utilize oncology PK early phase drug and biologic development expertise for the conduct of ETCTN PK assays; and
    • Plans, including benchmarks, to ensure effective interaction, communication, and monitoring of performance. Address such aspects as:
    • ·    Procedures and actions for failure to meet PK study timelines and objectives;
    • ·    Use and compliance with the ETCTN authorship guidelines for ETCTN-related publications (See: https://ctep.cancer.gov/initiativesPrograms/docs/ETCTN_Publication_Policy.pdf);
    • ·    Statistical analysis plans for clinical analyses related to PK and toxicity or outcome;
    • ·    Timely submission of required data to NCI centralized support; and
    • ·    Maintaining site personnel proficiency.

    Note: Supporting information pertaining to this Sub-section is requested under Other Attachments (see Section IV SF424(R&R) Other Project Information, subsection "Other Attachments", Attachments 1 and 2).

    Sub-Section C: Team Science for Project Development and ETCTN Participation

    The applicant will be expected to participate in multi-disciplinary scientific teams by providing expertise on PK studies during the development and implementation of ETCTN drug development plans. 

    Address such aspects as:

    • Assessing PK results for subsequent prioritization of agent development or dose escalation;
    • Experience participating in early drug and biologic development team science initiatives and inter-and intra-disciplinary team projects;
    • Enhancements of existing capabilities and new approaches to facilitate the goals of the collaborative team.
    • How the collective PK experience of the investigators will benefit ETCTN clinical trials and accelerate experimental therapeutic agent development; and
    • Educating ETCTN early career clinical investigators regarding clinical research pharmacology.

    Sub-Section D: Pharmacokinetics, Coordination of Specimen Collection, Tracking and PK Associated Activities

    In this sub-section, describe:

    • Approaches proposed to provide comprehensive PK characterizations of new anticancer agents. The proposed approaches should ensure extensive characterization of the liberation, absorption, distribution, metabolism and excretion of the drugs and biologics under evaluation in the ETCTN clinical trials.
    • Sample handling;
    • Coordinating the acquisition, handling, preparation, evaluation, and shipment of specimens to ETCTN sites and/or tumor banks/biorepositories when applicable;
    • Proposed management of complex PK studies for early phase clinical trials including data analysis plans and procedures;
    • Plans and procedures utilized to support the timely completion of early phase clinical trial PK studies 
    • Procedures for timely review and assessment of PK data, interim evaluation, and consideration of measures of outcome consistent with patient safety and Good Laboratory Practice (GLP) (https://www.fda.gov/ICECI/Inspections/NonclinicalLaboratoriesInspectedunderGoodLaboratoryPractices/ucm072706.htm) (See Section IV SF424(R&R), "Other Project Information", sub-section "Other Attachments", Attachment 4);
    • Plans to ensure timely submission of required data to NCI centralized clinical trial support systems, including plans to develop a module for reporting PK analysis on individual patients and the clinical trial patient population, as well as compartment modeling.
    • Procedures for high quality, on-site data management, including interactions with on-site and CTMS data management personnel, data transmittal via Medidata Rave to CTMS, data editing, timely resolution of queries from CTMS, quality control, and verification of submitted data;                                 
    • Use of an effective quality assurance (QA)/quality control (QC) program, including internal review and oversight of data submission; and
    • Procedures to ensure Conflict of Interest policies are consistent with PHS and NIH policies.

    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.
    • It is expected that these plans will address data compatibility. Formats, analytical algorithms, computational modeling and visualizations, and other bioinformatics tools resulting from this FOA are expected to be compatible with the NIH-approved bioinformatics platforms, such as those designed and implemented by the NCI Center for Bioinformatics platforms (http://cbiit.cancer.gov/data-sharing).
    • The data sharing plan is expected to ensure that ETCTN PK Laboratories provide any information/data that might be needed by ETCTN UM1 awardees to accurately and reliably assess treatment agent activity in patients.

    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 NIH-defined human subjects research, clinical research, and/or 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.

    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.

    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 the NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

    Use of Common Data Elements in NIH-funded Research

    Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies.  CDEs are data elements that have been identified and defined for use in multiple data sets across different studies.  Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records.  NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository).  NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection.  The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research.  Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

    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:

    The most crucial characteristics of the ETCTN Pharmacokinetics Resource Laboratories to be proposed under this FOA are their ability to provide the comprehensive PK analyses of NCI Investigational New Drug (IND) agents tested in ETCTN clinical trials at the requisite scale of at least 15,000 specimens per year as well as contribute their PK expertise to other aspects of these clinical trials.

    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?

    Specific for this FOA: What is the likelihood that the strategies proposed for pharmacokinetic analyses will significantly contribute to advancing the clinical development of NCI-IND agents?

    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? 

    Specific for this FOA: How strong are the expertise, experience, and ability of the team to analyze complex pharmacokinetic data and meet milestones and timelines? Does leadership show evidence of a collaborative, highly integrated, and effective program? Have the applicants made significant contributions to pharmacokinetic studies for early phase experimental therapeutic clinical trials? Is the level of clinical research-relevant administrative experience and skills that the PD(s)/PI(s) and other key personnel have in the organization adequate? Does the applicant provide adequate senior and other statistical support personnel for PK analysis? 

    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? 

    Specific for this FOA: Do the applicants propose novel or improved ways and/or methods to enhance or better conduct pharmacokinetic studies for early phase clinical trials?   

    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?  

    Specific for this FOA: Do the research strategy and communication plan demonstrate an appropriate understanding of pharmacokinetics in drug development and of the methodologies available to exploit these opportunities? Is the planned level of support for analyses and statistical analysis approach appropriate? Are the capabilities and procedures for data collection, data management, data analysis adequate and sufficient at the designated core laboratory?

    Are procedures to monitor and analyze the data sufficiently rigorous in terms of the safety of patients/participants? 

    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?

    Specific for this FOA: How valid and reproducible are the PK laboratory's quality assurance/quality control indicators?  Are sufficient support personnel available with the skills needed to implement PK laboratory studies and to analyze PK data for early phase experimental therapeutic clinical trials? How supportive are the proposed organizational structure and institutional environment for optimal communications, data collection/transmittal in an accurate and timely fashion, specimen transfer between the ETCTN sites, etc.? 

    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.

    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

    Not applicable.

    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 NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

    As part of the scientific peer review, all applications:

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

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

    Applications will be assigned to the NCI. 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.

    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’s 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:

    • Overseeing all the activities of the ETCTN PK laboratory;
    • Determining overall research strategy for ETCTN pharmacokinetic studies for early phase clinical trials:
    • Ensuring timely completion of PK analyses and reporting their results; and
    • Ensuring timely preparation, presentation, and publication of PK results and research findings.
    • Ensuring compliance with the applicable rules for the conduct of clinical research summarized in the following documents:
    • ·    NCI CTEP Investigator’s Handbook (Manual for Participants in Clinical Trials of Investigational Agents Sponsored by the Division of Cancer Treatment and Diagnosis, NCI) available at
    • https://ctep.cancer.gov/investigatorResources/docs/InvestigatorHandbook.pdf; and
    • ·    NCI Guidelines for Monitoring The Experimental Therapeutics Clinical Trials Network (ETCTN) and Other Early Phase CTMS-Monitored Studies at https://ctep.cancer.gov/initiativesPrograms/docs/ETCTN_Monitoring_Guidelines.pdf.

    The awardee is responsible for ensuring that the NCI CIRB will be the IRB of record for all studies

    conducted in the ETCTN.

    Required Systems Use: The investigator(s) will be required to use systems developed and maintained by NCI/CTEP. These systems are the Clinical Trials Monitoring System (CTMS), Cancer Trials Support Unit (CTSU), Identity and Access Management (IAM), Cancer Therapy Evaluation Program Enterprise (CTEP Enterprise), Medidata Rave (Theradex version), Technical Resources International (TRI), Oncology Patient Enrollment Network (OPEN), the NCI Early Phase Central Institutional Review Board (CIRB), ETCTN BioRepository (Nationwide Children’s ETCTN Biorepository and Accessioning Center), and WebReporting for aggregated Adverse Event analysis. See: https://ctep.cancer.gov/initiativesPrograms/etctn_infrastructure.htm

    Required Registration: For clinical study participation, site Clinical Investigators and all site Sub-Investigator research staff must register with the NCI and re-register annually using the Registration and Credential Repository (RCR). See: https://ctep.cancer.gov/investigatorResources/default.htm#guidelines_policies

    Staff must maintain an applicable, active person-registration status by submitting required documentation necessary for NCI to qualify research site personnel and to be added to the corresponding site roster in Regulatory Support Services (RSS) to allow for participation in the clinical investigations and to access all CTEP and CTSU websites and applications. Documentation submission requirements for qualifying personnel per person registration type are outlined on the CTEP website (https://ctep.cancer.gov/investigatorResources/default.htm).

    Awardees will retain custody of and have primary rights to the data and software developed under these awards, within the limits of any accepted binding NCI/NIH collaborative agreements with biotechnology and pharmaceutical partners and as governed by NCI-approved Data Sharing Plans and NCI-approved review for use of biospecimens collected in association with ETCTN trials. Custody of and primary rights to the data and software developed under these awards is subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. The NCI will have access to all data (including imaging data) collected and/or generated under this Cooperative Agreement and may periodically review the data.

    The Terms and Conditions of Award for all the Cooperative Agreements under the ETCTN define the operational principles under which the awardees must function to ensure the independence of the research conducted regardless of whether program income is or is not available for any of the awards. All key components of the ETCTN must report these “Program Income” to the NCI on an annual basis (in the non-competitive Type 5 application (Research Performance Progress Report (RPPR)) and must indicate the clinical trial PK study that the funds are being used to support (or other functional component if the funds are not provided to support specific trials).

    The PDs/PIs, as well as appropriate Co-Investigators, will become members of the IDSC and will be required to attend all IDSC meetings and are expected to serve on the ETCTN Pharmacology Task Force. (https://www.cancer.gov/about-nci/organization/ccct/steering-committees/investigational-drug.)

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

    Designated NCI Program Director(s) will have substantial involvement as a Project Scientist(s).

    Additionally, an NCI Program Director, acting as Program Official will be responsible for the normal,

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

    The main responsibilities of substantially involved NCI staff members include, but are not limited to, the following activities:

    • Working with awardees to collaboratively manage issues associated with their participation across the ETCTN;
    • Informing the PDs/PIs of scientific opportunities resulting from NCI-supported clinical research programs and facilitating collaborations between the ETCTN and other NCI-sponsored programs;
    • Auditing of ETCTN sites via their membership in the ETCTN;
    • Reviewing overall performance of ETCTN PK Laboratory activities by site(s);
    • Reviewing compliance with applicable HHS, FDA, OHRP, NIH, and NCI regulations;
    • Advising awardees concerning mechanisms established for quality control;
    • Monitoring PK Laboratory progress and performance;
    • NCI Leadership and NCI CTEP staff will review proposals from ETCTN investigators for correlative studies to enhance clinical trials and recommend approved studies for funding consideration; and
    • Reviewing all records related to awardees’ performance under the award for appropriate collection, review, and distribution of biospecimens collected in association with ETCTN trials.

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

    Areas of Joint Responsibility include:

    Experimental Therapeutics Clinical Trials Network. PDs/PIs of the ETCTN, NCI ETCTN Program Director(s)/Official(s), CTEP Medical Officers, and designated NCI staff will be members of the Experimental Therapeutics Clinical Trials Network. As part of the ETCTN, all members will:

    • Develop appropriate early phase experimental therapeutic clinical trial protocols.
    • Participate as active team members on drug development project teams led by IDB Medical Officers.  They will meet quarterly to review studies performed under the award and more often to participate on and provide input for the IDSC, with respect to the drug development plans.
    • Discuss and resolve any issues raised during the initial review of letters of intent
    • Collaborate on study development and conduct especially with respect to compliance with federal regulations for clinical trial research and participating in activities related to the collective management of the ETCTN, as appropriate.
    • Address other programmatic responsibilities jointly, as needed, by the ETCTN awardees and the NCI staff. 
    • General aspects of collaboration on study development and conduct especially with respect to compliance with federal regulations for clinical trial research (e.g., ensuring that when new avenues of cancer therapy involving investigational drugs are pursued, trials are designed, when appropriate, such that the clinical information obtained would be acceptable to the FDA for inclusion in a potential licensing application), conduct of Data and Safety Monitoring Boards (DSMBs) for randomized phase 2 trials and other trials with clear licensing potential, development of collaborative trials and international trials, collective management of the ETCTN.
    • Review of recommendations from the NCI Clinical Trials and Translational Research Advisory Committee (CTAC) on strategic directions for the ETCTN Program
    • PDs/PIs, including contact PDs/PIs, multiple PDs/PIs, co-investigators, will meet on a frequent basis to scientifically and financially manage the award. The cooperative agreement may function as a single institution or a consortium consisting of the contact PI and all other PDs/PIs. For early phase trials the meetings should occur weekly or more frequently if necessary, and on an ad hoc basis to review all ongoing patients and trials. Later phase studies should be managed every other week or less frequently, depending on the complexity of the planned clinical investigation. This ETCTN coordination committee/team will be charged with the safe conduct of clinical trials based on Good Clinical Practice principle and will assure that all regulatory requirements and reporting are fully met for all trials they are conducting. The NCI monitors and audits all these trials in their position as IND sponsor. The ETCTN coordination team will be responsible for reviewing all trials open in the ETCTN that they accrue to which are open at their institution and that appropriate disease specific experts are identified to champion all disease specific phase 1 and 2 trials. This group along with the study PDs/PIs are required to work collaboratively with NCI Program staff to assure that competitive proposals are discussed and submitted to CTEP for review and decision.

    The Investigational Drug Steering Committee (IDSC) is a body convened by the NCI Coordinating Center for Clinical Trials (CCCT).  The characteristics and activities of IDSC are outlined below.

    • The IDSC is constituted by the CCCT to include the following membership: 2 elected chairs, all cooperative agreement contact PD/PIs and other multiple PDs/PIs, ETCTN coordinators who liaise with the NCTN Groups, subject matter experts in the areas of biomarkers, molecular characterization, statisticians, pharmacologists, radiation oncologists, interventional radiologists, research pathologists and others added ad hoc based on need and expertise. Leadership of the trans-ETCTN Biospecimen Working Group (EBWG) will become members of the IDSC.
    • The IDSC has a coordination team (CT) consisting of 2 leaders elected from the membership of the IDSC, the NCI Program Director of the ETCTN, the Branch Chief of the Investigational Drug Branch, and other CT leaders.  
    • The main goal for IDSC is to facilitate ETCTN collaborations and provide scientific and technical expertise related to experimental therapeutics development.
    • The IDSC will work in concert with CTEP and the ETCTN Program Director to 1) further the goals and objectives to treat, control, and cure cancer, 2) clinically evaluate investigational agents with an emphasis on translational research to elucidate molecular targets and mechanisms of drug effects, 3) provide advice during all phases of drug development, and 4) facilitate scientific dispute resolution.
    • The IDSC will meet at least quarterly.

    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 ETCTN representatives 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 panel members. 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)

    For inquiries related to ETCTN management and trials, contact

    S. Percy Ivy, M.D.
    National Cancer Institute (NCI)
    Telephone: 240-276-6107
    Email: ivyp@ctep.nci.nih.gov

    For inquires related to science, contact

    Fernanda Arnaldez, M.D.
    National Cancer Institute (NCI)
    Telephone: 240-276-6565
    Email: fernanda.arnaldez@nih.gov

    Peer Review Contact(s)

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

    Financial/Grants Management Contact(s)

    For inquiries related to financial matters, contact

    Shane Woodward
    National Cancer Institute (NCI)
    Telephone: 240-276-6303
    e-mail: 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.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.