IMPORTANT NOTE: NIH
has published new limitations on grant application appendix materials to
encourage applications to be as concise as possible while containing the
information needed for expert scientific review.EXPIRED
Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)
Components of Participating Organizations
National Cancer Institute (NCI) (http://www.nci.nih.gov; http://ctep.info.nih.gov/)
Title: Early Clinical Trials of New Anti-Cancer Agents with Phase 1 Emphasis (U01)
Announcement Type
This is a reissue of RFA-CA-02-011, which was previously released on November 19, 2001.
Request For Applications (RFA) Number: RFA-CA-07-031
Update: The following update relating to this announcement has been issued:
The purpose of this Funding Opportunity Announcement (FOA) is to continue funding for early development clinical trials of investigational new anticancer drugs sponsored by the NCI Cancer Therapy Evaluation Program (CTEP). The NCI solicits applications from established centers with clinical and scientific experience and patient resources to perform Phase 1 single agent clinical trials, Phase 1 agent combination clinical trials, limited Phase 2 clinical trials, and pilot clinical trials of novel anticancer agents. In addition to the clinical evaluation of new agents, the objectives include the characterization of the effects of these agents on their targets. This objective is to be addressed through the integration of suitable biochemical, pathological, immunological, molecular, and/or imaging methods and correlating the effects of the agents with clinically relevant endpoints.
Table of Contents
Part I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates
Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting
Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)
Section VIII. Other Information - Required Federal Citations
Part II - Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Purpose
This Funding Opportunity Announcement (FOA) is designed to continue funding for early development clinical trials of investigational new drugs (IND) sponsored by the NCI Cancer Therapy Evaluation Program (CTEP). The NCI invites applications from established centers with clinical and scientific experience and patient resources to perform Phase 1 single agent clinical trials, Phase 1 agent combination clinical trials, limited Phase 2 clinical trials, and pilot clinical trials of novel anticancer agents.
The overall objective of this FOA is to accelerate access to new cancer treatment strategies for patients. In addition to the clinical evaluation of new agents, the objectives include the optimization of clinical trials design and proper assessment of agents targeted against defined cancer-relevant biomolecules and/or processes. These objectives are to be addressed through the integration of suitable biochemical, pathological, immunological, molecular, and/or imaging methods and by correlating those effects with clinically relevant endpoints.
Background
More than 500 agents are currently in clinical development worldwide as new therapeutics for oncological indications. Many of these agents are designed to exert anticancer properties by specifically affecting various newly identified molecular targets. The NCI supports a program to facilitate the early stages of development of cancer therapeutics. To be effective, this program must ensure that: (1) Phase I clinical trial designs are promptly adapted to accommodate new therapeutic approaches, (2) early clinical trials are conducted safely and efficiently, and (3) potentially useful doses and schedules are determined for further clinical trials to evaluate agent combinations and/or for Phase 2 testing. In addition, the early proof-of-principle clinical trials need to address the issue of target validation by optimizing agent administration regimens and by verifying expected effects on putative targets and/or downstream processes. The NCI continues to support clinical studies in the area of developmental therapeutics that involve strategies aimed at optimizing the targeting of critical cancer-relevant biomolecules and/or processes and parallel as well as complimentary pathways using novel combinations of new agents.
The NCI Drug Development Group (DDG) prioritizes anticancer agents for development by NCI-supported mechanisms based on expert review of data on new agents provided by NCI and non-NCI scientists. The DDG determines the use of NCI resources supporting pre-clinical development by the Developmental Therapeutics Program (DTP) and clinical development through the NCI Cancer Therapy Evaluation Program (CTEP). New agents that are evaluated by DDG come from different collaborating sources: DTP, industry, academia, and NCI’s intramural laboratories. After DDG approval, a CTEP Senior Investigator prepares a strategic development plan, which integrates the input from CTEP, the collaborator who provides the agent(s), the Investigational Drug Steering Committee (IDSC), and other experts, whenever appropriate. CTEP staff prepares and submits to the Food and Drug Administration (FDA) the Investigational New Drug (IND) application. Subsequently, CTEP staff members request, review, and monitor protocols for Phase 1 single agent clinical trials, Phase 1 combination clinical trials, limited Phase 2 clinical trials, and pilot clinical studies.
The Early Therapeutics Development Program (ETDP) funds and oversees new agent development for CTEP.
NCI currently sponsors over 130 investigational new drugs (INDs) as oncology agents. The NCI participates in the clinical development of anticancer agents provided by collaborating pharmaceutical/ biotechnology companies. Co-development is in the best interest of the public because it can speed the access to new cancer treatment strategies for patients. Advancing the scientific understanding of the approach and extending the possible indication(s) beyond those explored by the collaborating pharmaceutical/ biotechnology companies in clinical trials directed towards New Drug Applications (NDAs) is a high priority for the NCI. The NCI promotes exploration of important scientific questions in areas that: (1) are not the primary focus of for-profit companies; (2) involve investigational agent combination studies using more than one investigational agent from different for-profit collaborators; (3) maximize target inhibition; and (4) abrogate signaling through parallel and complimentary pathways in cancer cells.
The size and scope of the ETDP is demonstrated by the existence of approximately 100 ongoing collaborative agreements, which involve 60 pharmaceutical/biotechnology collaborators. Under the scope of these collaborations, CTEP prepares and submits approximately 15 IND applications to the FDA each year. Agents under evaluation include small molecules, antibodies, vaccines, targeted toxins, oligonucleotides, and gene transfer agents. The classes of agents studied include angiogenesis inhibitors, receptor tyrosine kinase inhibitors, signal transduction inhibitors, farnesyl transferase inhibitors, cell cycle inhibitors, histone deacetylase inhibitors, inducers of re-expression of critical tumor suppressor genes, agents directed at novel targets (e.g., proteasome and heat shock proteins), cancer vaccines, immunotoxins, and cytotoxic agents.
The cooperative agreement awards supported by the ETDP have facilitated the development of novel Phase 1 clinical trial designs, including such aspects as: (1) accelerated dose escalation schemes; (2) evaluation of defined biological endpoints; (3) assessment of direct effects on defined molecular targets or on the downstream consequences of such targeting; and (4) dose determining trials in patients with organ dysfunction. Other innovations supported through the ETDP include pharmacogenetic studies and evaluation of combinations of investigational agents.
By continuing the ETDP under this RFA, the NCI intends to fund approximately 14 sites dedicated to new agent developmental efforts with the emphasis on Phase 1 clinical trials. The awards for Early Clinical Trials of New Anti-Cancer Agents with Phase 1 Emphasis 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.
The Project Directors/Principal Investigators (PD/PIs) of these awards, the NCI Program Director(s), and CTEP Senior Investigators will be members of an Early Clinical Trials Network. This group will meet semiannually to review studies performed under the award and more often to participate on and provide input for the Investigational Drug Steering Committee (IDSC).
Research Goals
The overarching objectives of the ETDP to be addressed by all the applications submitted in response to this FOA include the following research elements;
Required Organization of Sites for Early Development of Anticancer Drugs
Sites for Early Development of Anticancer Drugs responding to this FOA may include single or multiple institutions, as needed, to propose, develop, and perform early clinical trials, and/or to analyze the results of such trials. Strong justification, evidence of well-established collaborations, and clearly described procedures must be supplied for multi-institutional applications.
The functions of specific required organizational components needed for each Early Drug Development Site are outlined below.
1. Research Administration Component
The Research Administration component will provide scientific and organizational framework and a single Coordinating Center for the entire program with the following specific main responsibilities:
2. Clinical Trials Support Component
The Clinical Trials Support component will be responsible for the following aspects of the program:
3. Pharmacokinetics/Pharmacodynamics Component
The Pharmacokinetics/Pharmacodynamics component will support the performance of the relevant laboratory testing using clinical specimens by the following activities:
4. Data Management Component
All the awarded Phase 1 sites must have the Data Management component, which will be responsible for:
Related NCI Initiatives
In addition to the Early Therapeutics Development Program, a number of other complimentary or supportive initiatives form an integrated NCI program of drug discovery and development focused on molecularly targeted new agents. These initiatives include the following programs.
Quick Trial Grant (R21)(http://grants.nih.gov/grants/guide/pa-files/PAR-06-451.html): This initiative is intended to support hypothesis-driven, investigator-initiated clinical trials that advance the scientific understanding of cancer treatment. This complementary funding pathway for clinical trials currently supports only 15 grants with Phase 1 trials of CTEP IND agents. Correlative studies pertinent to ETDP-sponsored U01 award that contribute to elucidation of therapeutic hypotheses may receive support through Quick Trial R21 mechanism. This mechanism should be considered for support of laboratory studies that are complementary to individual Phase 1 trials funded by the ETDP U01 cooperative agreements.
Translational Research Initiative (TRI) (http://ctep.cancer.gov/resources/trf.html): The TRI provides an acquisition mechanism (contract) to fund correlative studies characterizing specific effects of new agents on their targets in CTEP-sponsored clinical trials, including pharmacodynamic studies. The approved correlative studies must be linked to the CTEP-sponsored clinical trials being conducted with CTEP IND agents. The TRI supports personnel time and procedures directly related to the laboratory correlative investigations and the laboratory studies. Because the type of assays, probes, and tools may vary widely with the agents tested, these costs are not included in the funding under this FOA (see Application Procedures).
Specialized Programs of Research Excellence (SPOREs) (http://spores.nci.nih.gov/): These programs promote interdisciplinary investigations on specific tumor sites to move basic research findings from the laboratory to clinical settings, including support for discovery and characterization of molecular targets.
Cancer Diagnosis Program (http://www.cancerdiagnosis.nci.nih.gov/): This program stimulates and supports diagnostics research, resources and improved technologies to guide the choice of treatment for cancer patients.
See Section VIII, Other Information - Required Federal Citations for policies related to this announcement.
1. Mechanism(s) of Support
This FOA uses an NIH cooperative agreement award (U01) mechanism. In the cooperative agreement mechanism, the Principal Investigator (PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the PI, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award. This FOA is a continuation of the CTEP request for applications previously issued as RFA-CA-02-011.
As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.
This funding opportunity uses just-in-time budget concepts. It also uses the non-modular budget format described in PHS 398 application instructions (http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the Initial Budget Period and the Entire Proposed Period of Support is to be submitted with the application.
2. Funds Available
Total amount of funding that NCI expects to award through this announcement is approximately: $41,300,000 total costs for Fiscal Years 2008-2013. In FY2008, NCI intends to commit approximately $8,260,000 to fund 14 new and/or competing continuation grants in response to this FOA.
An applicant may request a project period of up to 5 years and a budget for direct costs up to $590,000 per year. Direct costs for individual awards are expected to range from $400,000 to 590,000 per year.
Facilities and administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation, see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-004.html.
Although the financial plans of the NCI provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
Section III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
You may submit an application (one per institution or collaborating institutions) if your organization has any of the following characteristics and meets the additional requirements specified below:
Only U.S. and Canadian institutions (*) are eligible to apply. Other Foreign institutions may participate in the program through collaborations with U.S. and/or Canadian applicant organizations.
Applicant institutions must be medical centers with clinical and scientific experience, patient resources, and infrastructure to support clinical trials. A center responding to this FOA must have an established structure with the following components:
1.B. Eligible Individuals
Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution to develop an application for support. Individuals from underrepresented gender, racial, and ethnic groups as well as individuals with disabilities are encouraged to apply for NIH support.
More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).
One PI must be designated as Coordinating Center PI .
The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills, and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.
Eligible Principal Investigators. PDs/PIs must be affiliated with an eligible U.S. or Canadian institution and should have M.D., M.D./Ph.D., D.O., Ph.D., or equivalent degree(s) and the track records of performing clinical investigations of anticancer agents and leading a team in early therapeutics development with the commensurate qualifications, experiences, and accomplishments.
Qualifications and availability of appropriate personnel resources:
2. Cost Sharing or Matching
Not applicable.
The most current NIH Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing.
3. Other-Special Eligibility Criteria
Applicant institutions may submit only one application in response to this FOA.
Section IV. Application and Submission Information
1. Address to Request Application Information
The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance, contact GrantsInfo -- Telephone: (301) 710-0267; Email: [email protected].
Telecommunications for the hearing impaired are available at: TTY 301-451-5936.
2. Content and Form of Application Submission
Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.
The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.
The applicant must demonstrate in its application the ability to meet the RESEARCH OBJECTIVES of the FOA and to meet the investigator responsibilities described in Section VI.2.A.1. The Research Plan (Items A-D, PHS 398 form) should not exceed 50 pages (excluding pages that describe the capabilities of Member Institutions). Standard operating procedures and policies of the Phase 1 Program (e.g., study monitoring, Data Monitoring Policy, Conflict of Interest Policy, etc.) should be included as appendices in the application, as specified below. For competitive renewals, all clinical trials (identified by protocol number) that were active during the current project period should be briefly described using a tabular format (see Section 1 below).
For applications submitted in response to this FOA, the standard PHS398 Research Plan (Sections A-D) is altered as follows:
Section 1: Preliminary Data (Progress Report for competing renewal applications). The application must include a Preliminary Data/Progress Report section, which at a minimum addresses the following:
Section 2: Qualifications:
Section 3: Research/Administration Component - Standard Operating Procedures for Clinical Trial Development, Coordination, and Oversight. A description of the procedures developed and utilized by the Phase 1 program to support the timely development of Phase 1 single agent clinical trials, Phase 1 combination clinical trials, limited Phase 2 clinical trials, and pilot clinical trials for adults with cancer. The clinical trials must be conducted in accordance with the instruction in 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 procedures specified below and should describe indicators of success in implementing the procedures:
Section 4: Clinical Trials Support Component - Standard Operating Procedures for Conducting Clinical Trials, Data Analysis and Quality Assurance. The following should be addressed:
Section 5: Pharmacokinetic and Pharmacodynamic Component - Research Strategies and Plans and Standard Operating Procedures for Effort Coordination. The research strategy and plans of the Phase 1 program for developing new treatment approaches for cancer through Phase 1 and pilot clinical studies should be described, including:
Section 6: Data Management Component - Standard Operating Procedures for Data Reporting and Regulatory Compliance. A description of the following should be provided:
Section 7: Collaborating Member Institutions (needed only for multi-institutional applications). Generally, this FOA encourages single institution-based Phase 1 clinical trials programs. Nevertheless, if the program has established and documented collaborations with other institutions for Phase 1 investigations, a multi-institution application is allowed. In such a case, the applicants must identify one of the participating institutions as a Coordinating Center (the program Headquarters).
A multi-institutional application should include a description of the criteria used to select collaborating member institution(s). Appropriate procedures should be described for monitoring performance of member institutions. These procedures should address, for example, accrual of adequate number of eligible patients to program trials, timely submission of required data, observance of clinical trial protocol requirements, contributions to clinical trial protocol development and conduct, authorship in Phase 1 program publications, and participation in program administrative and scientific committees. The procedures should also define actions to be taken in case of inadequate performance of a member institution. A table(s) should be included that summarizes key aspects of the performance of collaborating member institution(s) (e.g., accrual to program trials by year, enrollment of ineligible and in-evaluable patients, timeliness of data submission, timeliness of AdEERS reports submission, compliance with specimen submission, etc.). The application should include a brief description of how each Collaborating Institution meets the criteria established by the Phase 1 program for appropriate research capabilities and for acceptable performance (limited to two pages per Collaborating Institution), including, but not limited to the following:
Section 8: Budget Considerations: The budget for early clinical trials of new anti-cancer agents with Phase 1 emphasis should include (in addition to support for scientific leadership, administrative and regulatory activities, data management and analysis, etc.) the following:
Special Instructions Applications with Multiple PIs
Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan (Section I of the Research Plan in the PHS 398), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. The PD/PIs at the Coordinating Center and the collaborating institutions should have their roles and responsibilities clearly defined in the application.
If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Grant Award (NoA).
IMPORTANT NOTE: NIH
has published new limitations on grant application appendix materials to
encourage applications to be as concise as possible while containing the
information needed for expert scientific review.
For details on what items are generally allowed as Appendix materials see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html
Additional Appendix items specific to this FOA:
As described in Sections 1-7 above, the following items are recommended for inclusion as the Appendix: the standard operating procedures of the site with key policy documents (e.g., the Data and Safety Monitoring Plan and Conflict of Interest policy); the institutions protocols activated during the preceding award period or the last three years including templates if appropriate; publications, manuscripts accepted for publication and abstracts accepted for presentation; the most recent clinical trial study reports prepared
Foreign Organizations
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.
Several special provisions apply to applications submitted by Foreign organizations:
Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, and/or environmental conditions in other countries that are not readily available in the U.S. or that augment existing U.S. resources.
3. Submission Dates and Times
Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.
3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date(s): February 26, 2007
Application Receipt Date(s): March 26, 2007
Peer Review Date(s): June/July 2007
Council Review Date(s): October 2007
Earliest Anticipated Start Date(s): January 2008
3.A.1. Letter of Intent
Prospective applicants are asked to submit a letter of intent that includes the following information:
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 NCI staff to estimate the potential review workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning of this document (i.e., February 26, 2006). The earliest anticipated start date is January 1, 2008.
The letter of intent should be sent to:
Dr. S. Percy Ivy
Associate Branch Chief
Investigational Drug Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN Room 7131, MSC 7246
Bethesda, MD 20892 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery; non-USPS mail)
Telephone: (301) 496-1196
Fax: (301) 402-0428
Email: [email protected]
3.B. Sending an Application to the NIH
Applications must be prepared using the research grant applications found in the PHS 398 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 (for U.S. Postal Service express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).
At the time of submission two additional copies of the application and all the appendix materials in pdf format (on a single CD) must be sent to:
Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery; non-USPS service)
Telephone: (301) 496-3428
Fax: ( 301) 402-0275
Email: [email protected]
Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.
3.C. Application Processing
Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the NCI. Incomplete and non-responsive applications will not be reviewed.
The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.
Information on the status of an application should be checked by the PI in the eRA Commons at https://commons.era.nih.gov/commons/.
4. Intergovernmental Review
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. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.
Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.
The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.
Principal Investigators should request support for their effort on the IDSC. Up to 5% effort should be requested. Travel funds for four IDSC meetings per year will be provided from another source and should not be requested in the application.
6. Other Submission Requirements
Plan for Sharing Research Data
All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.
The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.
The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.
Sharing Research Resources
NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.
The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.
The NCI is developing a policy that will require Clinical Terms of Awards for clinical studies and trials when they are a component of the proposed research. The policy will require that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. The new policy will be posted in the NIH Guide prior to implementation. All funded applicants will be expected to adhere to the new policy.
Section V. Application Review Information
1. Criteria
The following will be considered in making funding decisions:
2. Review and Selection Process
Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NCI in accordance with the review criteria stated below.
As part of the initial merit review, all applications will:
Receive a second level of review by the National Cancer Advisory Board.
The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on the following criteria in order to assess the likelihood that the institutions participating in the Early Therapeutic Development Program will be able to meet their responsibilities described in Section VI.2.A.1 and will be successful in meeting NCI’s goal of supporting a group of experienced investigators from highly capable institutions to expeditiously develop and conduct Phase 1 and other studies for adults with cancer using state-of-the-art research tools. Each of these criteria should be addressed and considered in assigning the overall score, weighing them as appropriate. Note that the application does not need to be strong in all categories to deserve a high priority score.
Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the proposed efforts significantly advance the development of new cancer therapeutics?
Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?
Track Record of Early Clinical Trials (new applications) or Progress (Competitive renewal applications):
Research/Administration Component (Clinical Trial Development):
Clinical Trials Support Component (Data Analysis and Quality Assurance):
Pharmacokinetics and Pharmacodynamics Component (Research Strategies and Plans):
Data Management Component (Data Reporting and Regulatory Compliance):
Innovation: Does the project challenge existing paradigms of clinical research; address critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?
Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?
Team Qualifications specific to early clinical trials:
Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?
Collaborating Institutions (if collaborating institutions are involved):
2.A. Additional Review Criteria:
In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:
Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).
Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).
Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.
2.B. Additional Review Considerations
Budget: The reasonableness of the proposed budget/budget justification and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.
2.C. Sharing Research Data
Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by NCI program staff through an administrative review plan. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The NCI will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).
2.D. Sharing Research Resources
NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and athttp://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.
Release of data collected in a clinical trial conducted under a binding collaborative agreement between the NCI Cancer Therapy Evaluation Program (CTEP) and a pharmaceutical / biotechnology company must be in compliance with the terms of the binding collaborative agreement and must be approved by CTEP and the pharmaceutical collaborator. Release of the data is also subject to the terms of any contracts between the Phase 1 program and other entities, which cover any of the requested data.
Program staff will be responsible for the administrative review of the plan for sharing research resources.
The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.
3. Anticipated Announcement and Award Dates
Applicants will be notified about the disposition of their applications once the National Cancer Advisory Board completes its second level of review of the applications. The applicants can expect notification in September 2007.
Section VI. Award Administration Information
1. Award Notices
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.
The following documents (and any subsequent modification to them) are hereby incorporated by reference as terms of award. These documents describe the programmatic responsibilities for the conduct of the research supported by this cooperative agreement.
o INVESTIGATOR'S HANDBOOK, a Manual for Participants in Clinical Trials of Investigational Agents Sponsored by the Division of Cancer Treatment and Diagnosis, (DCTD), National Cancer Institute (http://ctep.cancer.gov/handbook/);
o Intellectual Property Option to Collaborator (http://ctep.cancer.gov/industry/ipo.html) or may be obtained from the Regulatory Affairs Branch, CTEP, DCTD, NCI, at telephone number (301) 496-7912.
Responsibilities of Research and Administration Component:
The Coordinating Center under the direction of the Coordinating Center PI, is responsible for coordinating clinical protocol development, protocol submission for review and approval, study conduct (including central data collection and analysis), quality assurance including quality control and study monitoring, protocol amendments/status changes, adherence to requirements regarding investigational drug management and federally mandated regulations and protocol and performance reporting. Specific responsibilities are listed below.
1) Organizational Structure and Standard Operating Procedures (SOPs): The Coordinating Center, with the guidance of the Coordinating Center PI(s) and an appropriate Phase 1 program Internal Committee that includes the PIs at collaborating institutions (if applicable), is responsible for development and maintenance of an organizational structure and SOPs for the Phase 1 program.
2) Clinical Trial Development: It is the responsibility of the program to develop the details of the research design, including definition of objectives and approaches, planning, implementation, analysis, interpretations, and conclusions of studies, and publication of results. The Coordinating Center is responsible, in accordance with the program’s SOPs, for the preparation and implementation of procedures for development and submission of Phase 1 program clinical trial protocols to the CTEP Protocol and Information Office in a timely fashion for NCI’s review and approval.
a) Clinical trial protocols should be developed, submitted, and implemented in accordance with the DCTD Investigator's Handbook" (http://ctep.cancer.gov/handbook/index.html).
b) Submission of program clinical protocols for review and approval by NCI should be preceded by a written Letter of Intent (LOI) to the CTEP LOI Coordinator declaring interest in conducting a particular study. LOIs should be submitted using the LOI template (http://ctep.info.nih.gov/guidelines/index.html).
c) The Coordinating Center is responsible for communicating the results of the CTEP Protocol Review Committee to relevant program members.
d) The Phase 1 program will not expend NCI funds to conduct any study disapproved by CTEP unless CTEP's disapproval has been modified by the arbitration process (see Section VI.2.A.4 Arbitration Process).
e) All clinical trials utilizing CTEP-sponsored investigational agents co-developed with a pharmaceutical collaborator shall be conducted in accordance with the terms of the Intellectual Property Option to Collaborators (http://ctep.info.nih.gov/industry/ipo.html) and the NCI Standard Protocol Language for Cooperative Research and Development Agreements (CRADAs) and Clinical Trial Agreements (CTAs).
f) The Phase 1 program’s SOPs should include timelines for the steps involved in the development and electronic submission of LOIs, Phase 2 concept proposals, and clinical protocols, and should include mechanisms for monitoring the performance of the Coordinating Center and program members in meeting these timelines. The program’s SOPs should also include corrective action plans outlining the steps to be taken when these timelines are not met. Data concerning the Phase 1 program’s performance in meeting timelines for protocol development should be provided in the Annual Progress Report and quarterly tabular updates.
3) Study Monitoring (http://ctep.info.nih.gov/monitoring/section2.html#2.2.2): The Phase 1 program is responsible for assuring accurate and timely monitoring of the progress of each study, and therefore must have standard procedures for timely data collection and data management consistent with the intensive data requirements and the need for rapid reporting necessary for Phase 1 and other studies. Standard procedures include (but are not necessarily limited to):
a) Precise tracking of patient accrual and adherence to accrual goals defined by clinical trial protocol. If the Phase 1 program wishes to continue accrual to a study beyond the total accrual goal for eligible and ineligible patients specified in the clinical trial protocol, the Phase 1 must seek approval from CTEP prior to continuing patient accrual. Accrual will be an important measure of success by the program and will also be considered in the context of using novel trials designs, such as accelerated titrations designs that accrue fewer patients than 3 X 6 cohort expansion studies, timely accrual and completion of study objectives outlined in the protocol.
b) Procedures for assigning dose level (for Phase 1/dose escalation studies) at the time a new patient is enrolled in a study, and assuring that the required observation period has elapsed before beginning a higher dose level.
c) Patient screening and assessment of patient eligibility and evaluability.
d) Adequate measures to ensure timely medical review and assessment of individual patient data.
e) Adequate measures to ensure timely submission of clinical trials data (e.g., adverse events, anticancer response, etc.) from Collaborating Institutions. These measures should include procedures for monitoring compliance with the Phase 1 program’s guidelines for data timeliness on an institution and a study basis, including summary reports of data submission timeliness to be used for Institutional Performance Review and to be used for study monitoring [e.g., by the Data and Safety Monitoring Committee (DSMC)]. These summary reports should also be included in the Annual Progress Report.
f) Rapid reporting of treatment-related morbidity/mortality information and measures to ensure communication of this information to all relevant parties. For investigational agents sponsored by CTEP, this involves reporting to IDB, CTEP AdEERS according to CTEP guidelines specified in each protocol (http://ctep.info.nih.gov/reporting/adeers.html).
g) Preparation of study monitoring reports describing patient accrual and demographics, data timeliness, toxicity, and other items as appropriate. Examples of study monitoring reports include reports prepared for study chairs, the annual reports for program meeting agendas, and reports for the DSMC.
h) Adequate policies and procedures for closure of studies. If the Phase 1 program wishes to close accrual to a study prior to meeting the initially established accrual goal, the interim results and other documentation should be made available to CTEP staff for review and concurrence prior to implementation of the decision. It is recommended that statistical guidelines for early closure be presented as explicitly as possible in the clinical trial protocol in order to facilitate these decisions. In the event that the DSMC has recommended early closure, DSMC procedures regarding notification of CTEP must be followed.
4) Quality Control of Phase 1 program clinical trials: Quality Control (QC) and Quality Assurance (QA) Programs are inherently linked. The Clinical Trials Monitoring Branch of CTEP provides direct oversight of CTEP-sponsored programs and Cooperative Group QA/QC programs. The Phase 1 program is responsible for establishing and implementing mechanisms to assure the accuracy and reliability of its clinical trials data. Quality control is a complex topic spanning the entire range of diagnostic and therapeutic modalities employed by the program. Key items that should be addressed concerning quality control procedures include:
a) Institutional performance evaluations. Performance factors to be considered include:
i) Accrual of adequate number of eligible patients onto program trials;
ii) Timely, accurate submission of required data;
iii) Rigorous adherence to clinical trial protocol requirements;
iv) Participation in study development and in timely publication of study findings;
v) Participation in Phase 1 program administrative and scientific committees and/or other program activities; and
b) Procedures will be in place for putting Collaborating Institutions on probation for inadequate performance and for removing such institutions from the Phase 1 program if performance is not adequate by the end of the probationary period or at any time that the institution (or participating site) does not meet established Phase 1 program standards.
c) Educational functions that address data collection, data management, and overall data quality. These aspects include, but are not limited to, the following elements:
i) Training for new Clinical Research Associates (CRAs) in the Phase 1 program’s data submission policies and ongoing training for all CRAs concerning changes to program procedures and instructions for data submission in new protocols;
ii) Instruction for Study Chairs on their responsibilities for study monitoring;
iii) Instruction for Collaborating Institution PIs and all members at participating sites on their responsibilities in complying with the Phase 1 program’s SOPs and Federal regulations at their institution; and
iv) Training/guidance should also be provided to all participants on how to comply with NCI/NIH policies and procedures (e.g., Ethics, Conflict of Interest, etc.) in addition to the policies and procedures of other governmental agencies important to the conduct of clinical trials (e.g., OHRP, FDA).
d) Procedures for central review of major elements that impact on the outcome of clinical trials. This will include central review of claimed responses and adequacy of imaging studies submitted by member institutions, central review of submitted data with determination of protocol compliance in dose administration and dosage modification, and additional review as necessary.
e) On-site Auditing: The Clinical Trials Monitoring Branch (CTMB, CTEP, NCI) is responsible for monitoring and oversight of the Phase 1 QA/QC programs. The Clinical Trials Monitoring Service (currently awarded as a contract to a company called Theradex ) administers the Phase 1 data management and auditing functions on behalf of CTMB.
i) On-site auditing of Phase 1 program Collaborating Institutions will occur approximately three times/year for studies assigned to CTMS monitoring, with the timing of audits to be based in part on Collaborating Institution accrual. The on-site audit will address issues of data verification, protocol compliance, compliance with regulatory requirements for the protection of human subjects and investigational agent accountability. For Phase 1 studies assigned to be CDS monitored, audits will be conducted as part of the cancer center/single institution audits at least once every 3 years or more frequently if warranted by accrual. NCI/CTEP reserves the right to conduct an on-site audit at any time.
ii) The Coordinating Center and Statistics and Data Management component will be responsible for logistical coordination and ensuring follow-up of audit findings.
iii) Any serious problems with data verification or compliance with Federal regulations must be reported to the Clinical Trials Monitoring Branch immediately. Otherwise, written reports by CTMS must be submitted within 4 weeks of each audit to CTMB.
iv) The Coordinating Center and Statistics/Data Management components will be responsible for coordinating development of and compliance with corrective programs in response to audits. If the NCI determines that a program Collaborating Institution failed to adequately comply with NCI guidelines for conduct of clinical trials, accrual of new patients to Phase 1 program protocols at the affected institution shall be suspended immediately upon notice of the NCI determination. The suspension will remain in effect until the Phase 1 program conducts the required audit and NCI accepts the audit report or remedial action.
v) The Coordinating Center will be responsible for notifying any affected participating institution of the suspension. During the suspension period, no funds from this award may be provided to the participating institution for new accruals, and no charges to the award for new accruals will be permitted.
5) Publications: Timely publication of major findings is central to the ETDP mission and is a primary means by which the Phase 1 program’s accomplishments can be evaluated.
a) The program will have timelines for the development of abstracts and manuscripts based on its clinical trials and should have mechanisms for monitoring the performance of the Phase 1 program’s components in meeting these timelines. Corrective action plans will be implemented when these timelines are not met.
b) Publication or oral presentation of work conducted via the Phase 1 program’s Cooperative Agreement requires appropriate acknowledgment of NCI support.
c) For publications using an agent supplied under a CRADA or CTA, the CTEP pharmaceutical collaborator will have an opportunity for review prior to submission as per CTEP Standard Protocol Language for CRADAs and CTAs. The NCI will have access to all data generated under this cooperative agreement and will periodically review the data. The awardee will retain custody and primary rights to the data consistent with current HHS, PHS, and NIH policies.
6) Phase 1 Program Meetings: The Coordinating Center is responsible for the organization of biannual meetings to review the program’s progress, establish priorities, and plan future activities. The awardee and up to two additional individuals are required to attend the Early Therapeutics Development Meetings sponsored by CTEP and the PIs are required to attend the bi-annual IDSC meetings. Additional meetings between Phase 1 program members and meetings with NCI staff may be held as needed. Relevant responsibilities for meeting organization include:
a) Arranging for appropriate meeting space and accommodations for attendees;
b) Developing and distributing meeting agendas;
c) Providing the Report of Studies to include information detailing patient accrual and demographics, data timeliness, toxicity experienced by study participants, and other items (e.g., outcome data) as appropriate. The Coordinating Center and Statistics and Data Management component are responsible for ensuring that copies of the Report (electronic and/or hard copy) are distributed to program members and NCI program staff.
d) Preparing summaries as appropriate after each meeting to be sent to program members and NCI program staff.
7) Phase 1 Program Communications: The Coordinating Center is responsible for establishing routine electronic communication with Collaborating Institutions to facilitate clinical trial protocol development and study monitoring and to facilitate the work of the Phase 1 Program’s Research Administration and Clinical Trials Support components. Relevant communication methods include web site postings, e-mail, teleconferences, and video conferences.
8) Compliance with Federal Regulations Concerning Clinical Research: The PI and Coordinating Center are responsible for ensuring that the Phase 1 program is in compliance with all applicable federal regulations concerning the conduct of research involving human subjects. Policies and guidelines to be addressed include:
a) OHRP Assurances: The Coordinating Center must assure that each participating site has a current, approved assurance on file with OHRP.
b) IRB Review of Phase 1 Program Protocols: The Coordinating Center must assure that each clinical trial protocol is reviewed and approved by each Collaborating Institution’s IRB prior to patient entry, and must ensure that each clinical trial protocol undergoes continuing review no less than once per year by the IRB so long as the clinical trial is active.
c) Assuring Appropriate Informed Consent: The Coordinating Center must assure that each patient (or legal representative) gives written informed consent prior to entry on study.
d) IRB Review of the Coordinating Center and Statistics and Data Management Component (http://www.hhs.gov/ohrp/humansubjects/assurance/engage.htm): An IRB should determine and document that the Coordinating Center and Statistics and Data Management component have sufficient mechanisms in place to ensure that (i) management, data analysis, and DSM systems are adequate, given the nature of the research involved; (ii) sample protocols and informed consent documents are developed and distributed to each collaborating institution; (iii) each collaborating institution holds an applicable OHRP-approved Assurance; (iv) each clinical trial protocol is reviewed and approved by the IRB at the collaborating institution prior to the enrollment of subjects; (v) any substantive modification by the collaborating institution of sample consent information related to risks or alternative procedures is appropriately justified; and (vi) written informed consent is obtained from each subject in compliance with HHS regulations.
e) Registration of Phase 1 program Investigators: The Coordinating Center is responsible for assuring that Phase 1 program investigators performing trials involving CTEP investigational agents are NCI-registered investigators (Form 1572) and Financial Disclosure Form. All orders for CTEP IND agents must be signed or co-signed by an NCI-registered investigator.
f) Adverse Event Reporting: The Coordinating Center is responsible for assuring timely reporting of all serious and/or unexpected adverse events. Adverse events should be reported using the CTCAEv3.0, which is the NCI’s standard language for reporting adverse events in clinical trials (http://ctep.cancer.gov/reporting/ctc.html). For investigational agents sponsored by CTEP, this involves reporting to IDB, CTEP via AdEERS according to CTEP guidelines specified in each clinical trial protocol (http://ctep.info.nih.gov/reporting/adeers.html).
g) Assuring that the Phase 1 program is in compliance with CTEP requirements described in the DCTD Investigators' Handbook for storage and accounting for investigational agents {including NCI/HHS Drug Accountability Records (DAR) procedures}, and is in compliance with FDA requirements for investigational agents.
9) Managing and coordinating the acquisition and shipping of protocol-specified tumor specimens and biological fluids (with relevant clinical data) to the appropriate laboratories for testing and to a tumor/specimen repository for storage of specimens for future correlative laboratory studies.
10) The Coordinating Center is responsible for establishing a Conflict of Interest Policy for the Group. This policy should ensure that there is no reasonable expectation that the design, conduct, or reporting of research conducted by the Group will be biased by any conflicting financial interest of an investigator. The policy should be in compliance with the general policies of the NCI and the NIH.
11) Fiscal management of the Phase 1 program, including:
a) Establishment of program arrangements with Collaborating Institutions to support Program-related activities at each Collaborating Institution;
b) Administration of the Pharmacokinetics/Pharmacodynamics component, including the process for selecting laboratories to perform specific studies (a competitive process is encouraged when feasible); and
c) Distribution of funds from the Research/Administration component to collaborating institutions to support special clinical research costs for patients accrued onto program clinical trials. Funds will be disbursed on a capitation basis upon documentation that the test(s) have been performed. It is anticipated that for each program protocol, the capitation formula for institutional reimbursement required to offset specific research expenses will be reviewed and approved by the Steering Committee.
12) Submission of annual progress reports to the NCI that describe activities and accomplishments during the previous year of the Phase 1 Program. The report will use the PHS 2590 and include:
a) A summary of the overall performance of the Coordinating Center and Statistics and Data Management component in meeting their responsibilities for clinical trial protocol development, study monitoring, and complying with Federal regulations;
b) Summary data on performance of each Collaborating Institution, including clinical trial accrual, quality and timeliness of submitted data, and involvement in clinical trial protocol development activities; and
c) Research plans, changes in procedures and/or staff, and the proposed budget for the coming year.
13) Procedures to allow non-Phase 1 program institutions to participate in the development and conduct of Phase 1 program trials in those limited situations in which an institution has distinctive expertise or capabilities that would contribute to successful conduct of a program study.
Data Management Component:
1) Data Management Policies and Practices: The responsibilities of the Statistics and Data Management component for data management related to study monitoring include the following:
a) Providing for central storage, security, processing and retrieval of study results;
b) Incorporating security features consistent with the guidelines of the U.S. Department of HHS;
c) Implementing procedures for backing up the Phase 1 program’s clinical and administrative data, including intermittent duplication of the database with storage at a remote facility;
d) Protecting patient confidentiality at all steps in the submission and analysis of clinical trials data and ensuring the technical integrity and security of the data management systems; and
e) Providing CTEP in a timely manner, upon the request of the Project Officer, true copies of data files and supporting documentation for all CTEP-supported protocols that have a major impact on patterns of care, as determined by CTEP.
f) Providing verification of pathological diagnosis in cases where known variability in the accuracy of histological diagnosis is a potentially serious problem and where pathology data may provide important prognostic information.
g) Providing review either concurrently or retrospectively of port films and compliance with protocol-specified doses for individual patients, where relevant. Determination of adequacy of radiation delivery with the assistance of their respective radiological physics center, whose functions usually include equipment dosimetry, periodic institutional visits, and other aspects of physics review.
h) Providing review of pharmacy orders, drug administration, flow sheets, and drug distribution with determination of protocol compliance in dose administration and dose modification.
i) Providing assessment of adequacy of protocol-specified surgical procedures through review of operative notes and study-specific surgical forms where relevant.
j) Providing assessment of adequacy of protocol-specified imaging procedures. This assessment may include methods for acquisition and display of images, methods for monitoring quality of image interpretation (including quantitative measurement of lesions), and methods of data archiving and retrieval as appropriate to specific studies.
k) Establishing quality assurance procedures for laboratory assays for pharmacokinetic and correlative studies. These procedures may include such elements as assay validation procedures, calibration curves, check samples, standards for accepting or rejecting data (e.g., Shewart charts), positive and negative controls, and external quality assurance. Procedures for ensuring patient privacy and sample tracking must be established.
l) Reporting of pharmacokinetic results in real time during the course of the study. The schedule for sample assay should be established in the written protocol.
2) Reporting of correlative study results: Timely reporting of data to CTEP using CTMS (see http://www.theradex.com/CTMS/ctmsmenu.htm) or CDS (see https://cdsweb.nci.nih.gov/cdsweb/loginPage.do).
a) Most Phase 1 program studies, using CTEP IND agents, will report bi-weekly using CTMS.
b) For some Phase 1 program studies using CTEP IND agents, CDUS Complete reporting procedures will be used, which capture demographic, adverse event information (by course), and response data.
Responsibilities of Collaborating Member Institutions:
1) Participation of Collaborating Institution investigators in Phase 1 Program activities, as evidenced by the following:
a) Offering eligible patients participation in program studies and entering sufficient patients to meet accrual targets.
b) Participating in research design and clinical trial protocol development, including:
i) Serving as clinical protocol Chairs or as members of protocol study teams; and
ii) Participating in the Scientific and Administrative Committees needed to support the Program’s research objectives.
c) Participation in meetings: Appropriately participating in the biannual meetings of the Program (and in other meetings as deemed necessary for performance of Program activities).
d) Following the Program’s SOPs for the conduct of clinical research.
2) Implementing the core data collection method and strategy of the Phase 1 program: It is the responsibility of each Collaborating Institution to ensure that the procedures for data submission for each clinical trial protocol are understood by investigators at the site and that protocol-specified data are submitted accurately and in a timely manner to the Statistics and Data Management Component.
3) Complying with mechanisms for quality assurance and quality control of therapeutic and diagnostic modalities employed in trials. Institutional responsibilities for quality control include, but are not limited to, the following:
a) Chemotherapy: Submission of appropriate data to allow determination of clinical trial protocol compliance in dose administration and dosage modification;
b) Diagnostic Imaging: Submission of appropriate imaging studies to allow central review of claimed responses and adequacy of imaging and to allow the imaging research objectives are met;
4) On-site Auditing: Participation in the on-site monitoring program established by the Phase 1 Program;
5) Human Subjects Protection: Each institution must be in compliance with OHRP and FDA regulations concerning protection of human subjects. Member Institutions must implement the procedures established by the Phase 1 program to meet OHRP and FDA requirements for the protection of human subjects. These include:
a) Assuring that the institution has a current, approved assurance on file with OHRP;
b) Assuring that each clinical trial protocol is reviewed by the institution’s IRB prior to patient entry;
c) Assuring that each clinical trial protocol is reviewed annually by the IRB so long as the protocol is active; and
d) Assuring that each patient (or legal representative) gives written informed consent prior to entry on study.
6) Adverse Event Reporting: Implementing the procedures established by the Phase 1 program for assuring timely reporting of all serious and/or unexpected adverse events.
7) Investigational agent responsibilities: Implementing the procedures established by the Phase 1 program for assuring that investigators performing trials involving DCTD Investigational Agents are NCI registered investigators (Form 1572) and for assuring that the program is in compliance with CTEP requirements described in the DCTD Investigators' Handbook for storage and accounting for investigational agents (including NCI/HHS Drug Accountability Records (DAR) procedures), and is in compliance with FDA requirements for investigational agents.
8) Submission of specimens: Acquisition and submission of protocol-specified tumor specimens, biological fluids, and relevant clinical data to the appropriate laboratories where these specimens will be tested or stored for future studies.
9) Serving as a resource for the conduct of protocol-specified laboratory projects (e.g., pharmacokinetic studies, tumor biology studies). The Phase 1 program Internal Committee will establish a process for the selection of the laboratories to perform these studies. These projects may be supported using the Pharmacokinetics/Pharmacodynamic Component of the Program or by independent funding.
10) Participating in Phase 1 program procedures for the timely publication of major findings.
11) Conflict of Interest: Complying with the Conflict of Interest Policy of the program to ensure that there is no reasonable expectation that the design, conduct, or reporting of research conducted by the Phase 1 program will be biased by any conflicting financial interest of an investigator.
Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
2.A.2. NIH Responsibilities
The NCI Project Scientist(s)/CTEP Program Director and additional relevant NCI staff, as needed will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The NCI Project Scientist/CTEP Program Director will be the main NCI contact for all facets of the scientific interaction with the awardees and will provide advice to the awardee on specific scientific and/or analytic issues. NCI Program Staff Responsibilities will include:
1) Monitoring Consortium progress. Actions necessary for monitoring may include, but are not limited to, the following: regular communications with the PI and staff; periodic site visits for discussions with awardee research teams; response audits to confirm therapeutic activity reported from a clinical trial; review of audit reports; observation of field data collection and management techniques; fiscal review; review of clinical trial reports submitted to NCI; review of the Phase 1 program’s annual progress report; and attendance at Phase 1 program meetings. The NCI retains, as an option, periodic external review of progress.
2) Scientific Liaison: Serving as a resource with respect to other ongoing NCI activities that may be relevant to the Phase 1 program research efforts to identify promising new leads, to facilitate compatibility with other NCI research projects, and to avoid unnecessary duplication of effort.
3) CTEP Assistance in Clinical Trial Development: The clinical trial protocol must be a detailed written plan of a clinical experiment mutually acceptable to the Phase 1 program and to the CTEP Protocol Review Committee (PRC). Communication at the various stages of protocol development is encouraged as necessary to promote protocol development and implementation. Protocols should be preceded by a written LOI from the Phase 1 program declaring interest in conducting a particular study. The PRC will formally review the LOI. Following review, the NCI Project Scientist/CTEP Program Director will provide a Program response to the Phase 1 program and will address the following issues: (a) the existence and nature of concurrent clinical trials in the area of research, pointing out possible duplication of effort; (b) information including relevant pharmacokinetic and pharmacodynamic data concerning investigational agents; (c) availability of investigational agents; (d) the PRC's assessment of the scientific rationale and value of the proposed study, its design, and statistical requirements; (e) appropriate inclusion of CTEP Standard Protocol Language for CRADAs and CTAs in the protocol; and (f) the implementation of the study, if indicated. The LOI mechanism is designed for preliminary review and is recommended to expedite clinical trial protocol development and implementation and to facilitate agreement on study priority and design (for further discussion of these mechanisms, see the DCTD Investigator's Handbook at http://ctep.cancer.gov/handbook/).
4) CTEP Review of Proposed Clinical Protocols: All Phase 1 program protocols will be reviewed by the PRC, which meets weekly and is chaired by the Associate Director, CTEP. Ad hoc reviewers, external to NCI, will be utilized when deemed appropriate by the PRC chairperson. Following the review of the clinical trial protocol by the PRC, the NCI Project Scientist/Program Director or staff will provide the Phase 1 program with a consensus review that describes recommended modifications and other suggestions, as appropriate (see the DCTD Investigator's Handbook, for further information regarding protocol review at CTEP). The major considerations relevant to Protocol Review by CTEP include:
a) Strength of the scientific rationale supporting the study;
b) Clinical importance of the question being posed;
c) Avoidance of unnecessary duplication with other ongoing studies;
d) Appropriateness of study design;
e) Consistency with development plans for particular IND agents;
f) Satisfactory projected accrual rate and follow-up period;
g) Patient safety;
h) compliance with federal regulatory requirements;
i) Adequacy of data management;
j) Appropriateness of patient selection, evaluation, assessment of adverse events, response to therapy and follow-up; and
k) Method of monitoring and reporting to NCI to be used, CTMS or CDS.
If a proposed clinical trial protocol is disapproved, the specific reasons for lack of approval will be communicated in writing by the NCI Project Scientist to the Phase 1 program as a consensus review within 30 days of protocol receipt by the NCI. NCI will not provide investigational agents or permit expenditure of NCI funds for a clinical trial that has not been approved. The NCI Project Scientist/CTEP Program Director or staff will be available to assist the Phase 1 program in developing a mutually acceptable protocol, consistent with the research interests, abilities, and strategic plans of the program and of the NCI.
5) CTEP Protocol Amendment Review: Any change to the protocol document subsequent to its approval by CTEP must be submitted in writing for review and approval prior to implementation (see Part 3: Attachment 9 The Investigator’s Handbook for further discussion of these procedures).
6) CTEP review of Audit Findings: Review of all audit reports (i.e., data audits and annual Phase 1 visits for studies assigned for CTMS monitoring and cancer center/single institution audits for trials assigned to be CDS monitored. The Clinical Trials Monitoring Branch will review audit results and the corrective plans developed by the program in response to the audits.
7) CTEP Involvement in Imaging Research: The NCI Imaging Research Coordinator will advise the program and the NCI Project Scientist/Senior Clinical Investigator with respect to ongoing NCI activities and research opportunities related to the application of imaging in drug development. He/she will participate in CTEP review of protocols with imaging components and will assist the NCI Project Scientist/Senior Clinical Investigator in the overall review of imaging research activities and accomplishments.
8) CTEP Involvement in Radiation Oncology Research: The NCI Radiation Oncology Research Coordinator will advise the ETDP and the NCI Project Scientist with respect to ongoing NCI activities and research opportunities related to radiation therapy for cancers. He/she will participate in CTEP review of protocols with radiation therapy components and will assist the NCI Project Scientist/Senior Clinical Investigator in the overall review of radiation oncology research activities and accomplishments.
9) CTEP Involvement in Clinical Trial Protocol Closure: Protocol closure is primarily the responsibility of the Phase 1 program and the specific Protocol Committee. The NCI Project Scientist/Program Director or staff will also monitor clinical trial protocol progress and may request protocol closure to further patient accrual for the following reasons: (a) insufficient accrual rate; (b) accrual goal met; (c) poor protocol performance; (d) patient safety or regulatory concerns; (e) study results are already conclusive; and (f) emergence of new information that diminishes the scientific importance of the study question. NCI will not provide investigational agents or permit expenditures of NCI funds for a study after requesting closure (except for patients already on-study).
10) Data Management and Analysis Review: Biometric Research Branch Staff will review mechanisms established for data management and analysis. When deemed appropriate, the Program Director or staff will make recommendations to ensure that data collection and management procedures are adequate for quality control and analysis and as simple as appropriate in order to encourage maximum participation of physicians entering patients and to avoid unnecessary expense. The NCI will have access to all data although they remain the property of the awardee institution. Data must also be available for external monitoring as required by NCI's agreement with the FDA relative to the NCI's responsibility as drug sponsor.
11) Data and Safety Monitoring Committees: The NCI Program Director, assisted by the Biometric Research Branch (BRB) staff, will assess compliance with NCI and NIH established policies on Data and Safety Monitoring Plans. The NCI Project Scientist must review and approve DSM Plan.
12) Phase 1 Program Meetings: The NCI Program Director and Project Scientist/Senior Clinical Investigator will attend biannual Early Therapeutics Development meetings to discuss relevant scientific information, to discuss progress in the clinical trials, and to discuss the status of newly available investigational agents and other research opportunities in order to plan future activities. Other NCI staff (e.g., from IDB, Radiation Research Program, and Biomedical Imaging Program) will attend as needed.
13) CTEP sponsorship of IND Applications: The NCI Program Director and Project Scientist, assisted by the Chief of the Regulatory Affairs Branch (RAB), CTEP, and staff will advise investigators of specific requirements and changes in requirements concerning IND issues that the FDA may mandate. Investigators performing trials under cooperative agreements will be expected, in cooperation with CTEP, to comply with all FDA requirements for investigational agents.
14) CTEP Review of Federally Mandated Regulatory Requirements: The CTMB and RAB through the NCI Program Director and Project Scientist, will advise the program regarding mechanisms to meet FDA and OHRP requirements for the protection of human subjects by program institutions.
15) Access to Data: The NCI will have access to all data generated under this cooperative agreement and may periodically review the data. Data must also be available for external monitoring as required by NCI's Drug Master File Agreement with the FDA relative to the responsibility of CTEP as an IND sponsor. The awardee will retain custody and primary rights to the data consistent with current HHS, PHS and NIH policies. The awardee will comply with the data access provisions of applicable CTAs and CRADAs, and when these agreements are in place the pharmaceutical collaborator will have complete access to the data for any and all regulatory filings.
16) Access to Agents for Pre-Clinical Testing: For CTEP-sponsored IND agents, CTEP will facilitate transfer of material to investigators with a Materials Transfer Agreement (MTA).
17) CTEP Review of Progress: Performance of each Phase 1 program will be reviewed at least annually by the NCI Program Director on the basis of the information provided at the semi-annual and other meetings, in the annual progress reports and in the CDUS reports submitted to CTEP for each of the clinical trials. Insufficient patient accrual or progress, or noncompliance with the terms of award, including these Terms and Conditions of Award, may result in a reduction of budget, withholding of support, suspension or termination of the award.
Additionally, an agency program official and/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.
2.A.3. Collaborative Responsibilities
The cooperative agreement awardee shall, with CTEP assistance as described in the above terms for the NCI staff responsibilities, develop appropriate early clinical trial protocols. The protocols must be acceptable to the CTEP Protocol Review Committee.
The Project Directors/Principal Investigators (PD/PIs) of the Phase I program awards, the NCI Program Director(s) and CTEP Senior Investigators will be members of an Early Clinical Trials Network. This group will meet semiannually to review studies performed under the award and more often to participate on and provide input for the Investigational Drug Steering Committee (IDSC).
Although it is envisioned that the majority of early clinical trials will be performed at a single site, awardees may collaborate to perform specific pharmacologic and correlative studies. For example, to minimize duplication of effort in assay validation and quality assurance procedures, researchers based at one Phase 1 program may perform correlative studies on biopsies provided by another Phase 1 program. CTEP scientists will assist investigators in the ongoing coordination required for such cross-award collaborations.
2.A.4. Arbitration Process
Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), excluding patient safety issues or regulatory compliance, between award recipients and the NCI may be brought to arbitration. An Arbitration Panel will be convened to review the CTEP decision and recommend an appropriate course of action to the Director, DCTD. The panel will be composed of the following three members: a designee of the awardee, one NCI designee, and a third designee with expertise in the relevant area who is chosen by the other two. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.
3. Reporting
Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 (http://grants.nih.gov/grants/funding/2590/2590.htm), annually, and financial statements as required in the NIH Grants Policy Statement. A suggested format for Phase 1 Program-specific information relevant to the progress summary section of the Form PHS 2590 will be provided. Performance of the program in developing new LOIs and protocols should be discussed, as should the performance of Member Institutions in participating in studies and the performance of reference laboratories. An update on clinical trials that were approved, activated, closed, and/or completed during the relevant budget period should be discussed in the progress summary and once a quarter in an abbreviated tabular format. Plans pertaining to clinical trial activities for the next budget period should be addressed as well.
Clinical trials reporting requirements will be in agreement with FDA regulations and NCI procedures. Interim reports of each activated and ongoing clinical trial should be prepared for each biannual meeting and shall include specific data on patient/participant accrual as well as detailed reports of treatment-associated morbidity. CTMS reports every 2 weeks. Information pertaining to CTMS monitoring is accessible at http://www.theradex.com/CTMS/ctmsmenu.htm. Quarterly accrual reports must be provided as appropriate to CTEP for all active trials through the NCI’s CDS. Instructions and Guidelines for CDS reporting are at http://cdsweb.nci.nih.gov/cdsweb/loginPage.do.
We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:
1. Scientific/Research Contacts:
Dr. S. Percy Ivy
Associate Branch Chief
Investigational Drug Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN Room 7131, MSC 7246
Bethesda, MD 20892 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery; non-USPS mail)
Telephone: (301) 496-1196
Fax: (301) 402-0428
Email: [email protected]
2. Peer Review Contacts:
Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery; non-USPS service)
Telephone: (301) 496-3428
Fax: ( 301) 402-0275
Email: [email protected]
3. Financial or Grants Management Contacts:
Barbara A. Fisher
Office of Grants Administration
National Cancer Institute
1003 West 7th Street, Suite 300
Frederick, MD 21701
Telephone: (301) 846-1015
Fax: (301) 846-5090
Email: [email protected]
Section VIII. Other Information
Required Federal Citations
Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.
Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); and efficacy, effectiveness, and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).
Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State, and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.
Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.
Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.html. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.
Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.
All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).
Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://stemcells.nih.gov/research/registry/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.
NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://publicaccess.nih.gov/) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from
NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.
NIH is requesting that authors submit manuscripts resulting from: 1) currently funded NIH research projects; or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.
For more information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_Manual.htm).
Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information," the "Privacy Rule," on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).
Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.
Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.
Authority and Regulations: This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 310 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CRF 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/policy.htm).
The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.
Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for 2 years to the research. For further information, please see http://www.lrp.nih.gov.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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