Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to fund one Pharmacokinetics Resource Laboratory (PK Laboratory) for the Experimental Therapeutics Clinical Trials Network (ETCTN) as a central resource to support all ETCTN sites participating in the network’s clinical trials. The ETCTN PK Laboratory will be responsible for the organization of biospecimen collection from all network sites as well as for the subsequent analyses of pharmacokinetic endpoints, drug-drug interactions, cytochromes P450 (CYP) interactions, pharmacodynamics, and food effects. This PK Laboratory will conduct all pharmacokinetic studies for ETCTN clinical trials involving Investigational New Drug (IND) agents under the regulatory sponsorship of NCI’s Division of Cancer Treatment and Diagnosis (DCTD), Cancer Therapy Evaluation Program (CTEP).  The ETCTN is funded through separate awards under the NOFO listed below.

• The ETCTN – Network Lead Academic Organizations under RFA-CA-27-016

Background

The ETCTN and its supporting infrastructure was established for early-stage clinical development of novel anticancer treatments that are then evaluated in clinical trials conducted under DCTD/CTEP IND in national, high-priority areas of unmet medical need. The ETCTN also uses NCI resources to molecularly characterized tumors to identify appropriate biomarkers that can be used to select patients most likely to respond to specific agents. ETCTN clinical studies determine the safety of 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. DCTD/CTEP currently holds approximately 210 INDs for investigational oncology agents/combinations which involve about 100 collaborative agreements with pharmaceutical/biotechnology companies. Agents under evaluation include, but are not limited to, small molecules, immune-oncology agents, antibodies, 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 include 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.

The ETCTN PK Laboratory provides the major resource for rapid, efficient, systematic evaluation and determination of the ADME profiles in patients participating in early phase ETCTN clinical trials. The ETCTN PK Laboratory is responsible for establishing pharmacokinetic profiles of DCTD/CTEP 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 Laboratory is responsible for studies that evaluate drug absorption, distribution, metabolism and excretion, pharmacodynamics, as well occasional studies to evaluate proof of mechanism and suitable patient candidates. The ETCTN PK Laboratory is expected to have: 

1. extensive experience, with access to multidisciplinary clinical and pharmacology experts, in performing PK analysis in high quality specimens in the context of early phase clinical trials according to Good Laboratory Practice (GLP) principles; 
2. established Standard Operating Procedures (SOPs) for data quality and laboratory quality control, including institute quality control for reagents and technologies for PK studies; 
3. capability to perform biostatistical/computational data analysis, interpretation, and compartment modeling for PK studies and to assess and analyze various pharmacodynamic parameters; and 
4. ability to serve as a resource center for the ETCTN to perform collaborative validation studies and provide technical and scientific expertise to ETCTN Project Teams for PK studies associated with drug development plans; and (5) ability to accept and transfer biospecimens from clinical trial sites in the U.S. and Canada. 

Interactions with Other NCI-supported Programs: In addition to NCI DCTD/CTEP staff and the ETCTN Lead Academic Organization and their participating sites, other NCI grant and contract-supported programs as well as NCI Program Advisory Committees having important supporting roles in carrying out the research objectives of the ETCTN. Thus, the PK Laboratory is required to interact, as appropriate, with such entities/programs as the DCTD Biometric Research Program (BRP); DCTD Cancer Diagnosis Program (CDP); Cancer Trials Support Unit (CTSU) with its Regulatory Support Services (RSS); NCI Central Institutional Review Board (CIRB); the ETCTN Clinical Data Management System (CDMS); the ETCTN Clinical Trials Monitoring Service (CTMS); and the NCTN Radiotherapy and Imaging Core Services Center (IROC).

Main Objectives and Requirements of this NOFO

Applicants for this NOFO are expected to have in place a standing infrastructure to support PK studies for ETCTN clinical trials from trial initiation through clinical development of NCI-IND agents. The ETCTN Pharmacokinetics Resource Laboratory application must include the following 3 functional components:

Technical Services Core - This functional component should provide the technical services for the full range of PK and associated assays and analyses needed to support ETCTN clinical trials.

Scientific Leadership and Project Development Core - This functional component should provide scientific leadership and expertise for a team-science approach to project development in support of PK activities for the ETCTN.

Biospecimen Collection, Tracking, Processing and Data Reporting Core - This functional Component should provide an integrated system/service for the collection, tracking, and processing of biospecimens from the ETCTN Lead Academic Organizations and their participating sites for ETCTN clinical trials. 

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

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

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)

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• 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. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; 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 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.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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 their organization to develop an application for 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 How to Apply - 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 trials of novel therapeutic agents and translational research. Proposed PD/PIs must be highly capable of interacting with inter- and trans-disciplinary team-based research with investigators involved in the design and conduct of clinical trials.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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

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 NOFO. 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 instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

For this specific NOFO, the Research Strategy Section is limited to 30 pages.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

Facilities & Other Resources: Provide a succinct description of the facilities and other resources/infrastructure that are available for the PK Laboratory. Include information on resources and resources/infrastructure that will be used for interactions with the ETCTN Lead Academic Organizations and their participating sites (e.g., information technology systems, logistical infrastructure, facilities for specimen receiving, tracking, and handling, etc.). The applicant should describe the storage facilities for biospecimens collected from national and international ETCTN trial sites and the analytical equipment available to perform pharmacokinetic studies and other analyses.  

Other Attachments: Applicants must provide the following attachments. Applications that do not include these attachments will be deemed incomplete and withdrawn by CSR before review. The filename provided must be used for each attachment, as it will become a bookmark in the application.

Attachment 1. PK Laboratory Communications Plans (use filename Communications)

• Outline proposed weekly, monthly, quarterly, biannually, ad hoc, and annual meetings that will be used to monitor biospecimen collection and tracking, as well as the progress and results of PK, pharmacodynamic, and other studies performed on ETCTN clinical trial biospecimens.

Attachment 2. PK Laboratory Organizational Charts (use filename OrgCharts)

• Outline of the organizational structure of the proposed ETCTN PK Laboratory (including all laboratory sites).

Attachment 3. PK Laboratory Performance Timelines (Use filename Timelines)

• Provide existing timelines (based on past performance) for pharmacokinetic study completion with references to submitted abstracts and manuscripts.   

Attachment 4. PK Laboratory Compliance with Good Laboratory Practice (use filename GLPCompliance)

• Provide a list of Standard Operating Procedures that the applicant 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 How to Apply - Application Guide must be followed.

Applicants should designate appropriate qualified senior/key personnel with significant responsibility for PK Laboratory operations. Applicants should also identify senior/key personnel who are statisticians with expertise in early phase clinical trial pharmacokinetic and pharmacodynamic studies.

R&R Budget

All instructions in the How to Apply - 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 Contractors that support the ETCTN. These services will be directly funded by the NCI. See: https://ctep.cancer.gov/initiativesPrograms/etctn_infrastructure.htm

In projecting costs, applicants should assume that the proposed ETCTN PK Laboratory will be required to process/analyze approximately 25,000 biospecimens per year. To justify the budget, applicants need to describe in detail the number of biospecimens expected for PK studies. For budget calculations, please note that the ETCTN is expected to have between each 4 to 6 ETCTN Lead Academic Organizations (LAOs) and each LAO is expected to accrue a minimum of 80 patients per year to early phase ETCTN clinical trials.

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 should not include or reflect any costs for the following activities:

• Correlative studies and biomarker assays to enhance specific clinical trials
• Any costs that are not solely research-related

Data Management: Cost for data management on site may be included. However, a clear justification must be provided to show that these costs are being incurred because the existing Clinical Trials Management System (CTMS) for data management that is provided by the NCI ETCTN program infrastructure is not sufficient to provide all needed data management for the proposed ETCTN PK Laboratory.

Funds for travel: Two representatives from the ETCTN PK Laboratory at least one of whom must be one of the PK Laboratory PD(s)/PI(s)] will be required to travel to at least one NCI/CTEP Early Drug Development (EDD) meeting per year for the purpose of enhancing communications between PK Laboratory PIs/Key staff and the ETCTN investigators conducting ETCTN trials and presenting key pharmacokinetic, pharmacodynamic, and other analyses from ETCTN trials.

Travel costs for two presenters for major national/international meetings should also 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.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Outline the specific aims of the proposed ETCTN PK Laboratory to perform comprehensive PK studies related to ETCTN studies evaluating novel anticancer treatments as well as other related assays/analyses including pharmacodynamics. These aims must be based on the demonstrated ability of the applicants to perform PK studies on about 25,000 biospecimens per year.

Research Strategy: Organize the overall Research Strategy section with sub-sections in the specified order and using the instructions below. Start each sub-section with the appropriate sub-section heading: Sub-section A. Overview; Sub-section B. Techical Services Core; Sub-section C. Scientific Leadership and Project Development Core; Sub-section D. Biospecimen Collection, Tracking, and Processing Core; and Sub-section E. Overall Progress Report (applicable for renewal applications only).

Sub-section A. Overview 

• Briefly describe the organizational structure and existing infrastructure of the PK Laboratory to support PK studies for the early phase clinical trials involving a wide spectrum of solid tumor cancers and hematologic malignancies to meet the scientific and clinical goals of the ETCTN.

Sub-section B. Technical Services Core 

• Summarize the PK Laboratory team's capability and experience in conducting PK studies for early phase clinical trial experimental therapeutic agents. Describe relevant team accomplishments and general capabilities to ensure extensive characterization of the liberation, absorption, distribution, metabolism and excretion of the drugs and biologics in clinical trials consistent with FDA Good Laboratory Practice (GLP).
• Provide specific information on the PK Laboratory's capability to develop validated PK assays with control standards and to provide timely comprehensive analyses of PK and pharmacodynamic data from clinical trials involving experimental cancer therapeutics. Information on the capability of developing and conducting other assays and analyses relevant for drug development may also be provided.
• Provide information on the PK Laboratory's ability to provide expert biostatistical/computational data analysis, interpretation, and compartment modeling for PK studies as well as statistical support for analyses related to PK, pharmacodynamics, toxicity, and outcome.
• Provide high-level summaries of important published results from clinical, translational, and/or basic research and other accomplishments of the Laboratory team with respect to the performance of PK studies for early phase clinical trials.

Sub-section C. Scientific Leadership and Project Development Core 

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

• The leadership and governance structure planned for integrating and coordinating activities for development and conduct of PK studies with ETCTN investigators/sites and other NCI-sponsored research
• Plans, including benchmarks, to ensure effective interaction, communication, and monitoring of performance
• Procedures and actions for failure to meet study timelines and objectives
• Use and compliance with ETCTN authorship guidelines for ETCTN-related publications (https://ctep.cancer.gov/initiativesPrograms/docs/ETCTN_Publication_Policy.pdf) 
• Policies and procedures to maintain proficiency of PK Laboratory staff and ensure Conflict of Interest policies for staff are consistent with PHS and NIH policies
• Plans for how the PK Laboratory team will provide scientific leadership and expertise to ETCTN investigators on PK studies to be included in drug development plans for new experimental agents (Project Development), emphasizing how the collective experience of the Laboratory team will benefit ETCTN clinical trials and accelerate the developmental process. Address the following specific elements:
  • Methods to assess results for 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; and
  • Plans to educate ETCTN early career clinical investigators on clinical research pharmacology.

Sub-section D. Biospecimen Collection, Tracking, Processing and Data Reporting Core 

• Describe the PK Laboratory's integrated system/service for the collection, tracking, and processing of biospecimens from the ETCTN Lead Academic Organizations and their participating sites associated with ETCTN clinical trials. Include information on biospecimen shipment, acquisition, handling, preparation, and evaluation.
• Describe how reporting of PK/pharmacodynamic analyses on individual patients and the clinical trial patient population, as well as compartment modeling, will be provided to NCI's centralized clinical trial support systems in a timely manner, including any plans for development of a module for direct electronic data transfer.
• Describe plans to ensure timely submission of required data to NCI centralized clinical trial support systems, including plans to develop a module for reporting PK/pharmacodynamic analysis on individual patients and the clinical trial patient population, as well as compartment modeling.
• Describe procedures for high quality, on-site data management, including interactions with on-site and Clinical Trial Monitoring Service (CTMS) data management personnel, data transmittal via NCI's data management system to CTMS, data editing, timely resolution of queries from CTMS, quality control, and verification of submitted data.
• Describe how quality assurance (QA)/quality control (QC) programs, including internal review and oversight of data submission, are incorporated at the PK Laboratory pharmacology.

Sub-section E. Overall Progress Report (applicable to Renewal applications only)

• The progress report should include a summary of the most significant achievements of the PK Laboratory in terms of conducting PK studies for ETCTN clinical trials and analyzing the results from those studies in a timely manner. The Progress Report should also emphasize how the PK Laboratory was able to provide expertise to ETCTN investigators regarding PK studies in new drug development plans and providing adequate biospecimen collection and tracking for the PK studies from the ETCTN Lead Academic Organizations and their participating sites.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format should not exceed two (2) pages. Where the DMS Plan Format Page requires a “Yes or No” response, no additional narrative is allowed.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - 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 How to Apply - 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 How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – 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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - 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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. 

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov. 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described 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 NOFO, note the following:

The most crucial characteristics of the ETCTN Pharmacokinetics Resource Laboratory to be proposed under this NOFO are its ability to provide comprehensive PK analyses of NCI DCTD/CTEP Investigational New Drug (IND) agents being evaluated in ETCTN clinical trials at the requisite scale of 25,000 biospecimens per year and to contribute its staff PK expertise to other aspects of ETCTN trials.

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).

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.

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.

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.

2. Review and Selection Process

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

As part of the scientific peer review, all applications will receive a written critique.

May undergo a committee 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.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director’s Statement of Priorities, entitled “Advancing NIH’s Mission Through a Unified Strategy.” 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for all activities of the ETCTN PK Laboratory as outlined below:

• Determining an overall research strategy for ETCTN pharmacokinetic and pharmacodynamic studies for ETCTN early phase clinical trials and overseeing all activities ot the ETCTN PK Laboratory
• Ensuring timely completion of PK and other analyses and results reporting to the ETCTN investigators overseeing the applicable clinical trials
• Ensuring timely preparation, presentation, and publication of results and research findings 
• Ensuring compliance with the applicable rules for the conduct of clinical research summarized in the following documents and any updates to the 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
  • 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.

PDs/PIs and the PK Laboratory staff will be required to use appropriate applications/electronic systems of the NCI DCTD/CTEP Enterprise system that supports the ETCTN, including, but not limited to, the Clinical Trials Monitoring System (CTMS), Clinical Data Management System (CDMS), and the Cancer Trials Support Unit (CTSU) as well as the ETCTN BioRepository and Accessioning Center. See: https://ctep.cancer.gov/initiativesPrograms/etctn_infrastructure.htm.

The PDs/PIs, as well as other appropriate PK Laboratory investigators will be members of the NCI Investigational Drug Steering Committee (IDSC) and will be required to attend IDSC meetings and serve on the ETCTN Pharmacology Task Force. See: https://www.cancer.gov/about-nci/organization/ccct/steering-committees/investigational-drug.

Recipients will comply with the NCI DCTD CRADA agreements and the Intellectural Property Option to Collaborators for ETCTN clinical trials conducted under a NCI DCTD/CTEP Investigation New Drug (IND) applications and/or Investigator Device Exemption (IDE). See: https://ctep.cancer.gov/branches/rab/intellectual_property_option_to_collaborators.htm.  

Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.

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

• Working with the recipients to collaboratively manage issues between the PK Laboratory and the ETCTN Lead Academic Organizations, their investigators, and their participating trial sites
• Informing the PDs/PIs of the PK Laboratory of scientific opportunities resulting from NCI-supported clinical research programs that might be relevant to PK Laboratory activities with the ETCTN and new mechanisms for quality control for PK activities
• Reviewing the performance of the activities of the PK Laboratory and its sites(s)
• Reviewing compliance with applicable HHS, FDA, OHRP, and NIH regulations
• Reviewing all records related to recipients performance for appropriate collection, review, and distribution of biospecimens collected form ETCTN trial sites

Additionally, an agency program official or NCI program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Designatied NCI Program Director(s) will have substantial involvement as a Project Scientist(s).

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

Areas of Joint Responsibility include:

• General aspects of PK Laboratory governance and collaboration with respect to quality assurance/control for PK studies and analyzes in ETCTN trials 
• Review of recommendations from the Investigational Drug Steering Committee (IDSC) and the ETCTN Pharmacology Task Force on strategic directions for improvements related to PK Laboratory activities and development of any action plans based on those recommendations.

• The IDSC will consist of the following voting members:
  • The PD(s)/PI(s) of each awarded CTEP’s ETCTN UM1 center will collectively have one vote.
  • The PD(s)/PI(s) of each awarded PK U24 laboratory will collectively have one vote.
  • Representative(s) from each NCTN group will collectively have one vote.
  • The subject matter experts in trial design, clinical imaging, radiation therapy, radiation therapy, pharmacokinetics/pharmacodynamics, cancer omics, health-related quality of life, and biostatistics will collectively have one vote.
  • The patient advocate(s) will collectively have one vote.
  • The NCI staff members will collectively have one vote.
• Additional NIH/NCI program staff and other government staff may participate in IDSC meetings as non-voting members.
• Two PD(s)/PI(s) will be elected to serve as co-chairs of the IDSC on a rotating basis following award issuance. All IDSC decisions and recommendations that require voting will be based on a majority vote. The IDSC provides recommendations for consideration by CTEP Program Officials.
• The Steering Committee may have additional non-voting members.
• Establish a transition plan to transfer data and procedures in the case that the PK Laboratory transitions to a new recipient after the conclusion of the award. 

Dispute Resolution:

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

3. Data Management and Sharing

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format should not exceed two (2) pages. Where the DMS Plan Format Page requires a “Yes or No” response, no additional narrative is allowed. 

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

eRA Service Desk - Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

NCI ETCTN RFA
National Cancer Institute (NCI)
Telephone: 240-276-5930
Email: NCIETCTNRFA@mail.nih.gov

 

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Office of Grants Administration
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: NCIFinancialContact@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.

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 2 CFR Part 200.