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

NCI Experimental Therapeutics-Clinical Trials Network with Phase 1 Emphasis (ET-CTN) (UM1)

Activity Code

UM1 Multi-Component Research Project Cooperative Agreements

Announcement Type

Reissue of RFA-CA-07-031

Related Notices

  • March 15, 2013 - See Notice NOT-CA-13-007. Notice of Pre-Application Teleconference Meeting.

Funding Opportunity Announcement (FOA) Number

RFA-CA-13-006

Companion Funding Opportunity

Not Applicable

Number of Applications

Only one application per institution may be submitted in response to this FOA; see 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 support an experimental therapeutics clinical trials program through the creation of a consolidated, integrated NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN). This FOA solicits UM1 cooperative agreement applications for multidisciplinary groups that will conduct early phase experimental therapeutics clinical trials. Members of the ET-CTN will work on investigational agent-specific trans-network project teams to define the drug development plan, and to conduct experimental therapeutic clinical trials filed to the Investigational New Drug (IND) applications by NCI’s Division of Cancer Treatment and Diagnosis (DCTD), Cancer Therapy Evaluation Program (CTEP).

The ultimate purpose of the ET-CTN is to define better approaches to the development of novel anticancer agents that capitalize on the ability to characterize tumors molecularly and find appropriate biomarkers to select patients most likely to respond to specific agents. The clinical trials to be conducted by the ET-CTN are intended to provide the dose, schedule, and early evidence of activity that will help guide disease-specific clinical trials to be conducted by the National Clinical Trials Network (NCTN), which will focus on controlled, randomized, Phase 3 trials.

Key Dates
Posted Date

February 8, 2013

Letter of Intent Due Date(s)

March 23, 2013

Application Due Date(s)

August 23, 2013     

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October - November 2013   

Advisory Council Review

January 2014  

Earliest Start Date

February 2014   

Expiration Date

August 24, 2013

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 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. While some links are provided, 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.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of 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


Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to transform the NCI-sponsored cooperative experimental therapeutics clinical trials program from a series of separate organizations conducting early phase cancer treatment trials into a consolidated, integrated NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN).  Members of the ET-CTN will work on investigational agent-specific trans-network project teams to define the drug development plan, and conduct experimental therapeutic clinical trials for agents with Investigational New Drug applications (INDs) held by the NCI Division of Cancer Treatment and Diagnosis (DCTD), Cancer Therapy Evaluation Program (CTEP, http://ctep.cancer.gov/).

The clinical trials to be conducted by the ET-CTN are intended to provide the dose, schedule, and early evidence of therapeutic activity including "proof of concept", "proof of mechanism", and target engagement/inhibition that will help guide disease-specific trials to be conducted under other NCI-supported programs, including the National Clinical Trials Network (NCTN) which will focus on controlled, randomized, Phase 3 clinical trials.

The NCI will facilitate formation of multi-institutional, multi-disciplinary project teams to establish a development plan for a series of trials for each novel agent to answer important questions. A drug development plan for each agent will be evaluated by the Investigational Drug Steering Committee (IDSC) run by the Coordination Center for Clinical Trials (CCCT) out of the Office of the Director. The IDSC is composed of ET-CTN contact PDs/PIs (awardees), subject matter experts, NCTN representatives, statisticians, pharmacologists, and NCI staff members with expertise in optimal early drug development. NCI representatives serve as non-voting liaisons. Emphasis will be placed on understanding and assessing both the molecular target(s) of the agent being studied as well as developing appropriate biomarker assays to select patients whose tumors are most likely to respond to the agent. The ET-CTN will focus on the pharmacokinetics (PK)/pharmacodynamics (PD), biomarker assays, and molecular characterizations of the majority of patients enrolled on its clinical trials, with an initial emphasis on genomic evaluation. Drug development will include assays for PD to define target engagement by the investigational agent. Investigators will collaborate with each other and with NCI staff to achieve ET-CTN objectives. The projects outlined in the drug development plan will be submitted as protocols for final approval to CTEP’s Protocol Review Committee (PRC). The ET-CTN will efficiently perform trials with new anticancer agents in compliance with the timelines established by the Operational Efficiency Working Group (OEWG).

ET-CTN members, sites, and selected external participants will have the opportunity to enroll patients on all trials conducted by the ET-CTN, irrespective of the specific ET-CTN site leading the trial. All participating sites will be responsible for monitoring and reporting patient safety information throughout the conduct of their clinical trials. NCI will provide standardized central operational, regulatory, and administrative support including data management, trial registration, and Central Institutional Review Board (CIRB) review for approved, early phase trials. 

The goals of the ET-CTN include:

Background

NCI's early therapeutics development program funds and oversees clinical development of new agents. The program has:

This program has been designed and implemented to ensure that: (1) early phase clinical trial designs can accommodate new therapeutic approaches; (2) early phase clinical trials are conducted safely and efficiently; and (3) potential doses and schedules are determined for use in patients in clinical trials to evaluate agent combinations and/or for Phase 2 testing. NCI currently sponsors 85 early phase clinical trials with novel agent combinations. Approximately two-thirds of the Phase 1 combination studies listed in ClinicalTrials.gov and in published literature have been conducted in the NCI Phase 1 program, which performs only cancer-relevant studies.

Through this program, the NCI promotes exploration of scientifically important clinically-relevant questions in areas that: (1) are not the primary focus of pharmaceutical companies; (2) involve investigational agent combination studies; (3) are aimed at maximizing target inhibition; (4) are aimed at abrogating signaling through parallel and complementary pathways in cancer cells; and (5) molecularly characterize patients’ tumors to further elucidate mechanisms of therapeutic response and/or resistance.

Through NCI’s Experimental Therapeutics Program, 540 INDs for investigational agents have been filed since 1972. CTEP currently holds approximately 100 INDs for investigational oncology agents which involve 60 pharmaceutical/biotechnology collaborators. CTEP prepares and submits approximately eight to fifteen IND applications to the Food and Drug Administration (FDA) each year. Agents under evaluation include small molecules, antibodies, vaccines, targeted toxins, oligonucleotides, and gene transfer agents.

In recent years, there have been unprecedented increases in the accumulation of data on mutations, epigenetic changes, and other "-omics" aspects with potential significance for various oncogenic molecular pathways.  This new information has led to the realization that assessing various cancer-relevant molecular abnormalities is essential for optimal and efficient development of targeted agents designed to exploit specific abnormalities in the therapeutic context. Combination studies with molecularly targeted agents have become an increasingly high priority for NCI, based upon evidence that resistance to initially effective single agents often develops quite rapidly in many adult tumors.

Overview of the Coordination of the Experimental Therapeutics Clinical Trials Network. To address the new opportunities and challenges in the development of novel targeted cancer therapeutics, the NCI has established a systematic approach with several interacting functional components. The NCI Experimental Therapeutics Program (NExT) is the portal through which NCI brings investigational agents into DCTD/CTEP for development. After a new agent is chosen for development, the Investigational Drug Branch (IDB) Project Team Leader will form an NCI Project Team from the various clinical, translational, and basic biology programs at NCI. Members of the Project Team will draft a preliminary drug/biomarker/assay development plan. Once this plan is reviewed and approved by the NCI Senior Advisory Committee (SAC), part of the NeXT-approved process, NCI will send out a request for Project Team Applications (PTAs) to the ET-CTN members, awardees of the NCI Phase 2 Contracts Program, NCTN awardees, and other appropriate investigators. The request for PTA will include publically available information about the drug being developed and the types and focus of the clinical trials being considered in the preliminary drug/biomarker/assay development plan. Once the PTAs have been reviewed and prioritized by NCI, the IDB Project Team Leader will constitute the Drug “X” Project Team with the PDs/PIs Lead Protocol Organization (LPOs), defined below, of the PTAs that have been approved as well as other relevant subject matter experts. This Drug “X” Project Team will be charged with refining the drug/biomarker/assay development plan for a team presentation to the IDSC. Following IDSC evaluation, the drug/biomarker/assay development plan will be finalized by the IDB and Letters of Intent (LOIs) will be requested from the Drug “X” project team. After approval of the LOIs by CTEP/DCTD, the protocols will be developed and submitted to DCTD/CTEP for final approval before activation.

NCI Organizational Groups Involved in the Early Experimental Therapeutics Clinical Trials Network

Several NCI organizational groups (branches/programs/services) will have important supporting roles in carrying out the research goals of the ET-CTN. The ET-CTN 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

Definitions

For the context of this FOA, several terms are used in specific meaning as defined below.

Terms related to the organization of ET-CTN:

Other terms related to the ET-CTN

Research Objectives

This FOA will support up to 10 ET-CTN sites dedicated to new agent developmental efforts with emphasis on early phase clinical trials. ET-CTN awards will provide the major resource for rapid, efficient, systematic evaluation and determination of optimal dose/schedule for specific agents and combinations of investigational agents sponsored under CTEP INDs. ET-CTN sites will also be expected to extensively characterize patient’s tumors on a molecular level to select appropriate patients for specific treatments, and to explore mechanisms of resistance and response to assist in defining follow-on treatment or determine future combination therapies.

Scope of Scientific Activities. Consistent with the objectives and priorities of the ET-CTN, each proposed ET-CTN site and its investigators need to be capable of clinical research involving the following main scientific activities:

Multi-disciplinary, Agent-specific Project Teams. The ET-CTN is designed to accomplish its objectives by forming multi-institutional, multi-disciplinary Project Teams, which will define early drug development clinical trials of novel drugs and/or combination therapies. All ET-CTN awardees will be expected to participate on Project Teams to define the development plans for specific novel agents/combinations relevant to their expertise and capabilities. Representatives of other NCI-supported programs will also participate on those teams. The NCI will coordinate and support logistically the formation and operation of the Project Teams. As novel agents progress from Phase 1 to Phase 2 clinical trials, investigators representing various relevant NCI-supported programs will collaborate with NCI’s Investigational Drug Steering Committee (IDSC) and its disease-specific steering committees. These Project Teams will develop novel treatments requiring molecularly guided patient selection and pathway-driven investigational combination therapies a wide variety of malignancies.

Additional NCI Support for the ET-CTN sites. The NCI/DCTD/CTEP will provide the ET-CTN awardees with standardized central operational, regulatory, and administrative support. This support will cover such activities as: data management, clinical trial registration, and Central Institutional Review Board (CIRB) review for approved, early phase trials. 

Required Organization and Capabilities of the Proposed ET-CTN Sites

Applicants responding to this FOA may include single or multiple institutions, as needed, to propose, develop, and perform early clinical trials, and to analyze the results of such trials. Each of the proposed functions of specific required organizational components for each ET-CTN site are outlined below.

Key Capabilities and Attributes of Required Components

For the outlined goals of ET-CTN, applicants responding to this FOA need to have appropriate capabilities and attributes. These aspects are defined below as key components that are expected to provide a scientific and organizational framework for the ET-CTN.

Experience in Conduct of Clinical Trials and Development of Experimental Therapeutic Agent

It is essential that investigators applying for the ET-CTN awards have considerable expertise and well documented experience and accomplishments (past performance) in the conduct of cancer clinical trials and clinical development of experimental therapeutics. This experience may be acquired through a past performance in the NCI Early Phase Clinical Trials Program with Phase 1 Emphasis. However, previous affiliation with the NCI Early Phase Clinical Trials Program with Phase I Emphasis is NOT required and all qualified applicants are encouraged to apply.

Scientific Leadership

Program Director(s)/Principal Investigator(s) (PDs/PIs) at the ET-CTN sites are expected to be national and international leaders in cancer related clinical trials of novel therapeutic agents, related clinical areas, and translational research relevant to such studies. PDs/PIs should also have documented administrative leadership experience. The emphasis is on a team science approach and the ability to establish productive collaborations among participating clinical and translational research investigators from the proposed ET-CTN site. ET-CTN awardees will be expected to interact with other ET-CTN sites as well as other relevant external programs. Each ET-CTN site will be required to establish a specific structure to oversee the conduct of early phase therapeutic clinical trials, ensure data safety monitoring, compliance with the required policies and regulations, and facilitate interactions with other ET-CTN and NCI staff.

Team Science for Project Development

Each ET-CTN site will be expected to lead and/or participate in multi-disciplinary scientific Project Teams formed during the development and implementation of ET-CTN drug development plans. This objective requires that ET-CTN investigators are highly capable of inter- and trans-disciplinary team-based research efforts, including potential for interactions with investigators from other ET-CTN sites, other NCI-sponsored programs, and NCI staff members.

Pharmacokinetic/Pharmacodynamic (PK/PD), Biomarker Assay, and Molecular Characterization of Patients

Each ET-CTN site must have the capability to support clinical trials by conducting various laboratory testing of clinical specimens as needed. In addition to the standard PK/PD determinations, the required capabilities include such aspects as: developing validated assays; using validated molecular imaging methods; ability to handle biospecimens for transfer to other ET-CTN sites or tumor banks/biorepositories; and participating in the molecular characterization of all patients enrolled on early phase therapeutics trials. The latter aspect includes the requisite expertise in acquiring fresh biopsy specimens from a high percentage of patients on trials (even if invasive procedures are required).

Coordination of Clinical Trials and Associated Activities

The research and managerial coordination component will be responsible for the organization and coordination for all aspects of clinical trials operations, implementation, and safe conduct. The administrative component shall collaborate with NCI support infrastructure to coordinate ET-CTN activities. (Key units of this supporting infrastructure are listed above in the Background section).

Research Pharmacy Management

It is essential that all ET-CTN sites have a dedicated component to conduct investigational drug pharmacy operations required to adequately fulfill obligations related to investigational agents.

Career Development and Mentored Training of Junior Investigators

Each ET-CTN site will be expected to organize appropriate career development and mentored training. The program should provide an adequate mentorship and/or training for new and junior investigators, including opportunities for trainees to lead clinical trials and participate in future ET-CTN activities and/or initiatives.

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 staff will assist, guide, coordinate, and/or participate in project activities.

Application Types Allowed

New

The OER Glossary and the PHS 398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NCI intends to fund approximately 10 awards, corresponding to a total cost of $8,500,000, for fiscal year 2014. Future year amounts will depend on annual appropriations.

Award Budget

Application budgets must not exceed $850,000 total costs/year.

Award Project Period

5 years

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

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are  eligible to apply but only if they are based in Canada.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply except for Canadian components.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Only U.S. and Canadian institutions are eligible to apply. Other Foreign institutions may participate in the program through collaborations with either U.S. or Canadian applicant organizations.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least6 weeks prior to the application due date.

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 PHS 398 Application Guide.

Provided that other all other qualification requirements are met, the PD/PI or LAO PD(s)/PI(s) may have any of the following degrees: M.D., M.D./Ph.D., D.O., or Ph.D. 

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 may be submitted in response to this FOA.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

1.            To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;

2.            Of an investigator-initiated application that was originally submitted to an RFA but not paid; or

3.            Of an application with a changed grant activity code.

Section IV. Application and Submission Information


1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS 398 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:

The letter of intent should be sent to:

S. Percy Ivy, M.D.
Investigational Drug Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
NCI Shady Grove
Room 5W458, MSC 9725
9609 Medical Center Drive
Bethesda, MD 20892-9725 (for Express mail, use Rockville, MD 20850)
Telephone: (240) 276-6107
Email: ivyp@ctep.nci.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission two additional copies of the application and all the Appendix files must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
9609 Medical Center Drive, Room 7W412
Bethesda, Maryland 20892-9750 (for Express mail, use Rockville, MD 20850)
Telephone: 240-276-6390
Fax: 240-276-7682
E-mail: ncirefof@dea.nci.nih.gov

Page Limitations

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed with the following exceptions or additional requirements.

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

A. Overview of Relevant Capabilities and Past Performance – 6 pages

B. Scientific Leadership & Site Organization – 12 pages

C. Team Science for Project Development – 6 pages

D. PK/PD, Biomarker Assays and Molecular Characterization of Patients – 6 pages

E. Coordination of Clinical Trials and Associated Activities – 12 pages

F. Research Pharmacy Management – 6 pages

G. Career Development and Mentored Training of Junior Investigators - 6 pages

Supplemental Instruction for the Preparation of Applications

The following sections supplement the instructions found in the PHS 398 Application Guide.

The application should be assembled and paginated as one complete document in the following order:

Face Page

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells

Detailed Budget for Initial Budget Period

Budget for Entire Proposed Period of Support

Budgets Pertaining to Consortium/Contractual Arrangements

Biographical Sketches

Resources

Research Plan

Specific Aims

Research Strategy with the following sub-sections:

Bibliography and References Cited

Protection of Human Subjects

Inclusion of Women and Minorities

Targeted/Planned Enrollment Table

Inclusion of Children

Vertebrate Animals

Select Agent Research

Multiple PD/PI Leadership Plan

Consortium/Contractual Arrangements

Letters of Support (e.g., Consultants)

Resource Sharing Plan

Appendix

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions for the application parts listed below.

Table of Contents

Modify Form Page 3 of the PHS 398 to replace standard sub-sections of "Research Strategy" with the following new sub-sections:

A. Overview of Relevant Capabilities and Past Performance

B. Scientific Leadership & Site Organization

C. Team Science for Project Development

D. PK/PD, Biomarker Assays and Molecular Characterization of Patients

E. Coordination of Clinical Trials and Associated Activities

F. Research Pharmacy Management

G. Career Development and Mentored Training of Junior Investigators

Detailed Budget for Initial Budget Period and Budget for Entire Proposed Period of Support

Follow the current PHS 398 instructions to provide a detailed budget (direct costs) for the entire application for the first 12-month period (Form page 4) and the entire proposed project period (Form page 5).

Use Additional Form Pages 4 and 5 to provide detailed separate budget information (first year and cumulative budgets for the entire project period) for the following individual application components:

Important Note on Budget: The requested budgets should take into consideration the standardized central operational, regulatory and administrative support provided by NCI. These services will be directly funded by the NCI and respective cost must not be included in the requested budgets.

The budget should include (in addition to support for scientific leadership, administrative and regulatory activities, data management and analysis, and travel, etc.) the following items:

1. Scientific Leadership and Site Organization Funds for travel. The LAO PD(s)/PI(s) will be required to travel to four IDSC meetings per year. Travel funds for two NCI/CTEP Early Drug Development (EDD) meetings per year for three representatives from the ET-CTN site (at least one of whom must be the LAO PD/PI and for two presenters for major national/international meetings should be included in the budget for Scientific Leadership.

2. PK/PD, Biomarker Assays, and Molecular Characterization Research Funds for laboratory studies (e.g., PK and PD studies) performed on specimens (e.g., blood, tumor tissue, buccal cells, etc.) obtained from participants enrolled on ET-CTN clinical trials. Include this within the PK/PD, Biomarker Assays, and Molecular Characterization of Patients budget pages. Note: Biomarker assays will be prioritized and funded separately through administrative supplements. Other biomarker assays will require other sources of funding.

Pharmacology and specimen acquisition to be allocated to support institutional 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 and shipping for PK studies, tumor tissue handling and shipping to the tissue bank or pathology component, and performance of research imaging studies).

3. Coordination of Clinical Trials and Associated Activities Research Funds to be allocated to support institutional 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 and shipping for PK studies, tumor tissue handling and shipping to the tissue bank, and performance of research imaging studies). Include this cost within the Coordination of Clinical Trials and Associate Activities budget pages.

The budget for early clinical trials of new anticancer agents with early-phase emphasis should include funding to be allocated to support research and development and ET-CTN collaboration (in addition to support for scientific leadership, administrative and regulatory activities, data management and analysis, etc.).

All costs for on-site data management using Medidata Rave and services provided by CTMS must be fully justified. The cost of mailing or handling research-related patient specimens, forms, and materials should be included. Other consulting costs should be outlined.

Coordination of Clinical Trials and Associated Activities (protocol development, and statistics and data management) for the institution(s) costs to support the non-accrual responsibilities associated with participating in early-phase experimental therapeutic clinical trials (e.g., CIRB submission, amendment distribution and continuing review, site training, pharmacy set-up, and site administration) that must be met even if patients are never enrolled on a study at an institution. An annual accrual rate of at least 50 patients per year should be assumed.

4. Career Development and Mentored Training of Junior Investigators Funds (approximately 3% of the total budget request) for activities to develop junior investigators/junior faculty through mentorship and other initiatives. Junior investigator career development and mentored training costs should be addressed in the research plan in the proposed budget.

Budgets Pertaining to Consortium/Contractual Arrangements

Budgets for affiliated consortium component organizations (i.e., “AOs”) must be provided as individual subcontractual budget pages following the PHS 398 instructions.

Resources

In addition to standard information, provide in this section documentation of important capabilities and available resources for specific functional components of the ET-CTN LAO. Relevant information may be provided in tabular form as listed below. Applicants are strongly encouraged to use, as appropriate, table templates provided at http://ctep.cancer.gov/investigatorResources/docs/RFA-CA-13-006_TABLE_TEMPLATES.PDF.

Template Table 1. Leadership Staffing: List the staff in specific leadership positions.

Template Table 2. Completed and Ongoing Phase 1 and Phase 2 Clinical Trials: List Phase 1clinical trials that have been completed during the last 5 years and of any ongoing clinical trials for which significant research findings are available. Include first-in-human studies and trials that determined dose and schedule for both single agents and investigational agent combinations. Phase 2 trial examples may be provided. A table is recommended that enumerates total actual accrual by year for each clinical trial described.

Template Table 3. Other Scientific Achievements for Clinical Trials

Template Table 4. List of PK/PD Assays and Molecular Characterizations Performed During Conduct of Early Phase Clinical Trials

Template Table 5. Summary Accrual for Screened and Treated Patients on All Early Experimental Therapeutic Clinical Trials.

Template Table 6. Summary of Letters of Intent (LOI) Submitted and Approved, and Protocols Submitted: List Phase 1 clinical trial protocol development activities during the last 5 years, including relevant dates and milestones for LOIs submitted, clinical trial protocols submitted, and clinical trials activated.

Template Table 7. Inclusion Enrollment Report: Provide data on annual patient accrual to early phase clinical trials by gender and race/ethnicity composition as for the PHS 398 Inclusion Enrollment Report form (http://grants.nih.gov/grants/funding/phs398/enrollmentreport.pdf). Group clinical trials by phase of study.

Template Table 8. Operational Timelines for Activation of Clinical Trial Proposals: List timelines for the LAO and any AOs (if applicable).

Template Table 9. Patient Accrual for Individual Clinical Trials: List actual timelines for specific steps in the clinical trial protocol development process, including accrual rate projected and achieved, total accrual, and study duration.

Template Table 10. Summary of Biomarker and Correlative Studies: List biomarker assays and other correlative laboratory studies performed on patient tissue during the previous 5 years, especially those that included surgical or image-guided biopsies.

Template Table 11. List of Procedures and Policies: List the relevant Standard Operating Procedures (SOPs) and LAO policies including, but not limited to: specimen acquisition and handling; tumor banking procedures and policy; Institutional Review Board (IRB) policies, Human Subjects Research Protections (HSRP) policies, safety, and pharmacovigilance procedures and policies, assay validation procedures, etc.

Research Plan

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Research Strategy: The Research Strategy should consist of the following sub-sections.

A: Overview of Relevant Capabilities and Past Performance

In this sub-section, applicants should summarize their ability and experience to conduct clinical trials and experimental therapeutic agent development. Describe relevant clinical and research activities related to the development of investigational agents either held under IND in collaboration with the NCI or performed as part of other academic pursuits.

B: Scientific Leadership and Site Organization

In this Sub-section, describe the qualifications and experience of the scientific leadership, their plans for participating in ET-CTN activities, and the organization of the proposed ET-CTN site.  

Specifically, applicants are required to address, at a minimum, the following aspects:

Scientific Leadership

ET-CTN Site Organization:

C: Team Science for Project Development

ET-CTN sites will be expected to lead and/or participate in multi-disciplinary scientific teams during the development and implementation of ET-CTN drug development plans. In this section, describe relevant experience of the applicant team in the conduct and management of team science projects. Address plans with regard to such aspects as:

Provide an example of an inter- and trans-disciplinary team project focused on early drug development (ongoing or previously completed).  The example should demonstrate cooperation and coordination among investigators across disciplines in the investigation of a research question in a coherent fashion. The roles for each team member and the methods and/or processes that the team utilizes to promote a team effort in answering complex research challenges should be clearly articulated. These activities should demonstrate enhancements of existing capabilities and new approaches to reach the goals of the collaborative team.

This example may include, but is not limited to, the description of activities such as:

The example to be provided is for purposes of peer review only. There is no expectation that the project described will be implemented or funded within the ET-CTN. It will serve as a representative example of the groups’ ability to select and constitute a highly multi-disciplinary team project. Examples that go beyond the LAO to include organizations involved in early phase experimental therapeutics are encouraged.

D: PK/PD, Biomarker Assays, and Molecular Characterization of Patients

In this section, outline expertise in PK/PD and acquisition/analysis of clinical specimens. Describe unique molecular characterization capabilities available at ET-CTN sites that can be utilized to analyze patients on ET-CTN trials. Address such elements as:

For patient molecular characterization, applicants should describe their expertise in the acquisition and analysis of high quality clinical specimens. Describe also experience, expertise, and procedures for validating and conducting studies using genomics, expression, analysis, or other assay-driven integral biomarker evaluations such as:

E: Coordination of Clinical Trials and Associated Activities

Applicants should describe their experience and the proposed management of complex early phase clinical trials, including protocol development, patient accrual, data and specimen management, and compliance with regulatory statutes. Clinical trials must be conducted in accordance with the Investigator’s Handbook, A Manual for Participants in Clinical Trials of Investigational Agents Sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute (http://ctep.cancer.gov/handbook).

The application should address the items specified below:

Protocol Development and Clinical Trial Execution

Data Management

Regulatory Compliance

Data Formats

Protocol templates utilized by the ET-CTN should be referenced using appropriate websites such as the CTEP website, or included in the appendix.

F: Research Pharmacy Management

Describe plans for investigational pharmacy operations to fulfill obligations related to investigational agents.  Summarize the existing/implemented and planned policies and procedures regarding the following elements:

Infrastructure/Equipment

Inter-institutional pharmacy exchange and secondary distribution of investigational drugs are NOT permitted.

G: Career Development and Mentored Training of Junior Investigators

A description of career development and mentored training in experimental therapeutics education and training for junior investigators (less than 7 years post oncology fellowship training) is required in this section. The proposed activities should include adequate mentorship and/or training for new and junior investigators that provides opportunities for the trainees to lead clinical trials and participate in future ET-CTN activities and/or initiatives. Training should provide opportunities to enhance skills in conducting clinical trials, skills in molecular pharmacology, and learn principles of clinical development of experimental therapeutics. Translational research (“bench to bedside” and “bedside to bench”) should be an integral part of these activities. Define and career development and mentored training activities in experimental therapeutics program for Junior Investigators.

The development of junior faculty through mentorship is expected to include such activities as:

Describe any relevant activities and opportunities that will be available to junior investigators in the environment of the proposed ET-CTN site:

Protection of Human Subjects: In addition to standard items indicated in the PHS 398 Application Guide, include in this Section SOPs and policies of the proposed ET-CTN related to study monitoring, data monitoring, and conflict of interest issues.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modifications:

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.

Foreign Institutions

Foreign (non-U.S.) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS 398 Application Guide.

(Note that the only foreign institutions eligible to apply in response to this FOA are Canadian institutions.)

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS 398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

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

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information


1. Criteria

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

The overarching goal of this FOA is to bring novel anticancer agents into early therapeutic clinical trials for cancer patients. This goal requires investigators with outstanding leadership, robust infrastructure, and a strong record of conducting clinical trials. Particularly important for the clinical development of current generations of experimental cancer therapeutics is the ability to integrate clinical trials with translational approaches and additional clinical studies, including the ability to obtain and analyze PK/PD and biomarker data in all patients enrolled on all studies. Essential for ET-CTN will be the awardees' ability to work as part of a network. In this context, the important aspects are whether the applicants have assembled a team of investigators capable of conducting state-of-the-art early phase therapeutics trials and PD-pilot studies in patients with cancer, and whether they will be able to work as a coherent research team to efficiently and expeditiously conduct early phase clinical trials.

Overall Impact       

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the proposed ET-CTN site 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 ET-CTN site 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 program that by its nature is not innovative may be essential to advance a field.

Significance

Does the proposed ET-CTN site address an important problem or a critical barrier to progress in the field? If the aims of the proposed ET-CTN site 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: Will the ET-CTN site, as proposed, be able to introduce appropriate novel anticancer agents into oncology clinical trials in a timely, safe, and efficient manner? 

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the proposed ET-CTN site? If Early Stage Investigators or New Investigators, or 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:

Does the project have adequate biostatistical expertise to conduct and analyze complex clinical and molecular data?  How complete and comprehensive is the expertise of the PD(s)/PI(s) and the entire team of investigators assembled by the applicant(s) in terms of their ability to conduct state-of-the-art early experimental therapeutics studies in patients with cancer? How well do the research experience and qualifications of the PD(s)/PI(s) correspond to the need for multi-disciplinary capabilities (e.g., in medical oncology, radiation oncology, imaging, surgery) and across a broad range of cancer types? 

Will these investigators be able to work as a coherent research team to efficiently and expeditiously conduct early phase clinical trials?

Do the PD(s)/PI(s) demonstrate the ability to facilitate collaborations between ET-CTN investigators and other clinical/translational science investigators? 

Do the PD(s)/PI(s) have sustained, high-level participation in the scientific leadership of early experimental therapeutics (e.g., serving as scientific  committee or protocol/trial study chairs, contributing new trial ideas including participating in LOI development, co-authoring publications on clinical trials research)?

What is the ability of the PD(s)/PI(s) to contribute in a meaningful way to the development of clinical trials in rare cancers? 

How capable are the PD(s)/PI(s) of providing meaningful contributions to translational research, PK/PD, biomarker assays, and molecular characterization integral to or integrated into the ET-CTN clinical trials?

Do the PD(s)/PI(s) have adequate and appropriate experience in administering clinical trial research, including organization and management of the infrastructure required for patient recruitment/accrual, data collection, data reporting, and safety monitoring for patients enrolled on clinical trials?

Are the other key personnel appropriately trained and well suited to carry out the work associated with early clinical trials?

Is there sufficient and appropriately experienced support personnel available for the proposed ET-CTN site with the skills needed to develop, implement, and analyze early phase experimental therapeutic clinical trials?

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 early clinical trials? 

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?  

Specific for this FOA:

Are the overall strategy, methodology, and analyses well reasoned and appropriate to accomplish the specific aims of the ET-CTN site?

How strong are the overall approaches proposed for individual components of the ET-CTN? 

Do the research plans demonstrate an appropriate understanding of research opportunities in drug development and of the methodologies available to exploit these opportunities?

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?   

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.

Relevant Capabilities and Past Performance

How strong are the applicants’ expertise and experience in early phase clinical trials for patients with cancer? Specifically, how adequate is this experience in terms of collection, management, and analysis of data from single institution or multi-institution clinical trials? What is the level of applicants’ experience in performing independent response auditing?

How productive were the applicants in terms of the timeliness of the development, implementation, and completion of recently conducted early phase clinical trials?

How accomplished are the applicants in terms of their research contributions (documented by peer-reviewed publications) to multi-institutional early phase experimental therapeutic clinical trials and dissemination of the results of such research?

Leadership, Governance, and Site Organization

To what extent are the proposed leadership and governance structure, decision-making processes, and interactions among key investigators optimal for designing and conduct of multi-disciplinary, multi-institutional clinical trials in a range of cancer types and special populations?

For applications designating multiple PD/PIs, is the leadership approach, including the designated roles, responsibilities, governance, and organizational structure consistent with the aims of the project and the expertise of each of the PD/PIs?

How well are defined the plans for an appropriate governance structure to coordinate activities related to the ET-CTN across the various disciplines and departments at the LAO institution? 

Are the proposed leadership efforts and activities  reasonably distributed across such areas as patient enrollment, clinical data collection and management? Are these efforts optimally balancing the various disciplines and the roles of clinical departments involved in the clinical trials at the proposed ET-CTN site)? Are these plans in line with the proposed workload and anticipated accrual to clinical trials to ensure/enhance participation in ET-CTN trials by various disciplines at the LAO?

Is the staffing plan appropriate to ensure the efficient governance of the proposed ET-CTN site?

Are the organizational plans for the LAO sufficient and optimal to ensure the LAO’s ability to develop, propose, implement, and monitor ET-CTN clinical trials?

How appropriate is the proposed organization to ensure monitoring the performance of the affiliated clinical sites (AOs) in an ongoing manner?

How adequate is the ET-CTN organization in terms of supporting other aspects of early clinical trials and related activities? How well is the organization of the proposed ET-CTN site matched to its leadership (especially for applications designating multiple PD/PIs)?

Team Science for Project Development

How strong is the potential of the applicants for team science approaches to developing and implementing ET-CTN’s early phase experimental therapeutic studies?

At what level will the proposed ET-CTN site be able to participate (and/or lead) inter- and trans-disciplinary team-based research efforts, including potential for interactions with investigators from other ET-CTN sites, other NCI-sponsored programs, and NCI staff members?

PK/PD, Biomarker Assays, and Molecular Characterization of Patients

Are the proposed plans and capabilities for incorporating PK/PD, and pharmacogenomic endpoints into the clinical trials appropriate and sufficient?

Are the proposed plans and capabilities for incorporating molecular characterization endpoints into the clinical trials appropriate? In particular, is the scope of such efforts sufficient, given the goal to include in these characterizations a high fraction of patients participating in clinical trials? Are the plans and capabilities for incorporating imaging endpoints into the ET-CTN’s overall research program sufficient? How strong is the applicants’ understanding of the potential of imaging studies to aid drug development?

Coordination of Clinical Trials and Associated Activities

Protocol Development and Clinical Trial Execution. How appropriate are the overall coordination efforts for ensuring timely development of clinical trial protocols and clinical trial execution? Are the measures planned to maintain the proficiency of institution personnel in the management of early phase experimental therapeutic clinical trials clearly defined and sufficient? How appropriate and adequate are the mechanisms of periodic review of QA/QC, data management procedures, and safety monitoring? Will the proposed ET-CTN site have appropriate statistical expertise and support? How appropriate are study designs for early phase experimental therapeutic clinical trials that the applicants used previously? How appropriate are statistical designs for early phase clinical trials proposed for the ET-CTN? Do the ET-CTN sites have sufficient statistical support and utilize appropriate statistical design approaches for early experimental therapeutic clinical trials?

Correlative Studies. Does the applicant demonstrate the ability to obtain, process, and store high-quality specimens? Does the applicant demonstrate the ability to analyze and report on specimens from PK/PD and/or molecular characterization studies?

Data Analysis, Quality Assurance/Quality Control, and Reporting. Are the applicants’ capabilities for the analyses of data from multi-institutional clinical trials sufficient for the expected scale of activities? Does the application demonstrate adequate procedures to monitor and analyze the data and assure the safety of patients/participants? Are the QA/QC procedures adequate and sufficient to ensure the accuracy, integrity, and security of clinical trials data? Does the application demonstrate adequate procedures to review, analyze, and report data on serious and expedited adverse events? Are procedures for reporting of data from early phase clinical trials to CTEP using CTMS electronic data capture system sufficiently timely and reliable? Are all the critical needs for the required regulatory compliance adequately addressed?

Research Pharmacy Management

Are the resources, facilities, and equipment for research pharmacy management (including appropriate secure storage units) sufficient and in line with all applicable regulations? Do the proposed plans adequately address the needs for proper procedures for handling of experimental agents and maintaining all associated documentation? How complete is evidence  that Research Pharmacy in the proposed ET-CTN site will (a) adhere to all applicable regulations with regard to investigational agent handling, (including transport and disposal); and (b) will maintain proper documentation and record keeping, transport, etc?

Career Development and Mentored Training of Junior Investigators

Is there adequate institutional commitment to mentorship, training, and support of junior investigators in experimental therapeutics? What are the overall quality and expected effectiveness of the mentoring plans? How well do the plans incorporate the opportunities for junior investigators to learn the principles of early clinical development of experimental therapeutics and participate (or lead) relevant clinical trials, participate in scientific committees, etc?  How sufficient is the intended training in translational research? How valuable are for the ET-CTN goals other training and educational opportunities available to junior investigators? 

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

When the proposed ET-CTN site involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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 l

As applicable for the ET-CTN site 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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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) Genome Wide Association Studies (GWAS).

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.

How well are the applicants' budget projections aligned with the program objectives and proposed scale of operation? Are the funding allocations for PK/PD studies reasonable, appropriate, and not duplicative of other institutional funding?

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:

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

Applications will be assigned to the NCI and 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:

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

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 the DUNS,  SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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:

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

An NCI Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may be designated to have substantial involvement (e.g., in the role of Project Managers). The NCI Project Scientist(s)/Managers(s) will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

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. Some Program Officials may also have substantial programmatic involvement (as Project Scientists/Coordinators). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NCI waiver as stated above.

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

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 NCI may also review all records related to awardees’ performance under the award for appropriate collection, review, and distribution of biospecimens collected in association with ET-CTN trials.

In case of insufficient patient accrual per the protocol specified, inability to meet the scientific aims of the Cooperative Agreement, or noncompliance with the Terms and Conditions of Award, the NCI reserves the right to reduce award budget, withhold support, suspend, or terminate the award.

Areas of Joint Responsibility

The cooperative agreement awardee shall, with CTEP assistance, develop appropriate early phase experimental therapeutic clinical trial protocols. Principal Investigators (PIs) of the ET-CTN awards, NCI ET-CTN Director(s), and CTEP Senior Investigators (Project Scientists) will be members of the ET-CTN.

ET-CTN sites will be expected to participate as active team members on drug development project teams.  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 development of drug development plans. Areas of joint responsibility include:

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 ET-CTN Group representatives chosen from the ET-CTN Leadership 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.

Note that in addition to these general rules for dispute resolution, a specific appeal process will be in place for decisions regarding approval of ET-CTN study proposals and the types of studies supported by the ET-CTN.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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. 

Section VII. Agency Contacts

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

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone (301) 435-0714
TTY (301) 451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: (301) 402-7469 or (866) 504-9552 (Toll Free)
TTY: (301) 451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

S. Percy Ivy, M.D.
Investigational Drug Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
NCI Shady Grove
Room 5W458, MSC 9725
9609 Medical Center Drive
Bethesda, MD 20892-9725 (for Express mail, use Rockville, MD 20850)
Telephone: (240) 276-6107
Email: ivyp@ctep.nci.nih.gov

Peer Review Contact(s)

Referral Officer
Division of Extramural Activities
National Cancer Institute
9609 Medical Center Drive, Room 7W412
Bethesda, Maryland 20892-9750 (for Express mail, use Rockville, MD 20850)
Telephone: 240-276-6390
Fax: 240-276-7682
E-mail: ncirefof@dea.nci.nih.gov

Financial/Grants Management Contact(s)

Shane Woodward
Office of Grants Administration
National Cancer Institute
9609 Medical Center Drive
West Tower, 2W462
Rockville, MD  20850
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 Parts 74 and 92.  

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