This notice has expired. Check the NIH Guide for active opportunities and notices.

EXPIRED

Part I Overview Information

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://cancer.gov/)
National Institute of Neurological Disorders and Stroke (NINDS) ( http://www.ninds.nih.gov/)

Title: Limited Competition: Adult Brain Tumor Clinical Trials Consortium (U01)

Announcement Type
 This Funding Opportunity Announcement (FOA) is a reissue of RFA CA-04-001, which was previously released on January 16, 2003.

Update: The following update relating to this announcement has been issued:

Request For Applications (RFA) Number: RFA-CA-08-504

Catalog of Federal Domestic Assistance Number(s)
93.394, 93.395, 93.396, 93.853

Key Dates
Release Date: December 27, 2007
Letters of Intent Receipt Date: January 29, 2008
Application Receipt Date: February 29, 2008
Peer Review Date: June/July 2008
Council Review Date: October 2008
Earliest Anticipated Start Date: December, 2008
Additional Information To Be Available Date (URL Activation Date): Not Applicable.
Expiration Date: March 1, 2008

Due Dates for E.O. 12372

Not Applicable.

Additional Overview Content

Executive Summary

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 Limited Competition Request for Application (RFA) is intended to continue support for Phase 1 and 2 treatment studies in adults with primary central nervous system cancers and to continue the activities that were funded initially under RFA CA-04-001. The ultimate purpose for supporting the Adult Brain Tumor Consortium is to improve treatment outcomes for adults with brain tumors.

This Funding Opportunity Announcement (FOA) solicits a single, consolidated application from the two currently funded separate adult brain tumor consortia: New Approaches to Brain Tumor Therapy (NABTT); and North American Brain Tumor Consortium (NABTC). The main objective of the consolidated Consortium is a safe and efficient introduction of promising new agents and treatment regimens for adult brain tumors. The conduct of well-designed Phase 1 and 2 clinical studies serves as a means to achieving this objective.

Background

High grade, primary brain tumors in adults remain refractory to surgery, irradiation, and systemic treatments. While all three modalities will likely continue to play a role for the foreseeable future in combating these tumors, continued optimization of these approaches individually, and in combination, is required. Annually, 20,500 primary brain tumors are diagnosed leading to 12,740 deaths in the United States (U.S.). These tumors are the second leading cause of death in people ages 15-34, the fourth leading cause in males 35-54, and the fifth leading cause of death in females ages 20-39. The current NCI-sponsored adult brain tumor consortia, NABTT and NABTC, have played a key role in demonstrating that studies of new agents can be carried out in patients with brain tumors. The successful completion of multiple clinical trials by the consortia has clearly increased the willingness of biotechnology and pharmaceutical firms to pursue clinical development of their new agents in brain tumors.

Over the last two award cycles (i.e., a 10-year period), NABTC and NABTT combined have enrolled over 2000 patients on nearly 50 Phase I/II trials (approximately 30% Phase 1 and 70% Phase 2 studies). An early clinical trials apparatus, focused on testing new agents in this medically challenging group of patients, remains an essential interface between early discovery mechanisms (e.g., Specialized Programs of Research Excellence [SPORE] programs, P01 program projects, R01 research projects, CTEP’s Phase 1-2 new agent evaluation program, pharmaceutical industry new agents) and the late trials mechanisms typified by the NCI-supported Clinical Trials Cooperative Groups. The multi-center clinical trials conducted by the Consortia have advantages over single institution trials in efficiency and creditability. To improve the success rate of drug discovery, the next generation of Consortia studies will require an increased emphasis on pre-clinical correlations, pharmacokinetic/pharmacodynamic (PK/PD) relationships, and evaluation of mechanistic endpoints based on tissue, imaging, and biomarkers.

This Limited Competition RFA builds upon experience accumulated during the prior funding periods of both NABTT and NABTC and is based on the following principles:

1. A limited number of experienced institutions with proven patient accrual capabilities are optimal for conducting Phase 1 clinical studies in patients with brain tumors. Single institution studies in adult brain tumors too often have insufficient capability for timely patient accrual, whereas Phase 1 clinical trials involving excessive numbers of participating institutions tend to be inefficient as well as sub-optimal in terms of monitoring and assuring patient safety.

2. To translate progress in cancer biology into benefit for patients with brain tumors, it is essential that appropriate Phase 1-2 clinical studies involving new agents/approaches are developed and implemented in a timely manner. This goal requires committed investigators as well as staff experienced in the development of clinical trial protocols. Efficient procedures must be in place with clearly defined timelines for completion of each step in the development of clinical trial protocols and their implementation. In addition, the research agenda must be focused on high-grade (3-4) glioma since this is the most common and lethal type of adult brain tumor. While commendable, research on other central nervous system tumors (e.g., lymphomas and low-grade gliomas) should be a limited part of the overall agenda.

3. Data from brain tumor Phase 1 and 2 studies must be of the highest attainable quality. This aspect requires committed, trained staff at local member institutions, effective mechanisms for rigorous data collection and analysis, and mechanisms for on-site audits to verify reported data and to assure compliance with clinical trial protocol.

4. Establishing correlations between agent doses and their effects on specific bio-molecules and/or cellular processes is important when developing new targeted agents. However, ethical considerations restrict tumor samplings that are intended strictly for research purposes. Therefore, the Consortium must be able to employ appropriate clinical trial designs that will ensure gaining relevant information on the targeted characteristics of such agents while avoiding undue risks to study participants. Examples of such trial designs include window-of-opportunity trials, studies of surrogate tissues, noninvasive imaging, etc.

5. Pharmacokinetic studies are central to exploring the likelihood that agents penetrate the blood-brain barrier and reach the brain tumor. Relationships between systemic drug exposure, brain tumor exposure, and target modulation may already be identified in preclinical models and/or in other adult tumors. Such information can provide benchmarks for estimating the intracranial drug levels and tumor exposures that should be targeted in a given trial in adults with brain tumors.

6. The Consortium must be able to introduce novel imaging methods into its adult brain tumor trials. This aspect is supported by the National Institute of Neurological Disorders and Stroke (NINDS). Development of neuro-imaging in brain tumors may have benefits for other brain disorders, and NINDS support will encourage incorporation of novel methodology and analyses that will hopefully further cross-disciplinary collaboration. Imaging methods have substantial potential for providing information in a non-invasive manner on the effects of anticancer drugs/agents on physiological processes within tumors. The Consortium should apply appropriate state-of-the-art imaging methods to brain tumor drug development. This endeavor requires procedures and resources for central collection, analyses and archiving of research images. It also requires the capability and commitment of each participating institution to perform imaging studies in a manner that strictly conforms to the requirements of the Consortium’s clinical trial protocols.

7. Pilot studies of promising multi-agent regimens (which may or may not involve a dose escalation) are a key step in the integration of new agents into the therapy of adult brain tumors. These studies require careful monitoring for toxicity and safety, which can be provided by the Consortium’s member institutions. Development and conduct of pilot studies requires close coordination between the study Principal Investigators (PIs) and the Consortium’s Operations Center / Statistical and Data Center.

8. Institutional members of the Consortium should be selected and maintained as members based upon objective criteria and upon impartial assessments of their abilities to contribute both scientifically and through patient accruals to the Consortium.

9. Drug development for adults with brain tumors is facilitated by a balanced public-private partnership. Reliance on support for this process entirely or mainly from the pharmaceutical industry increases the risk that new agents might be prioritized according to a company’s willingness to contribute rather than on the scientific merit of a particular agent or treatment regimen. It is important in the process of drug development for brain tumors that the pharmaceutical industry supports, but does not supplant, the NCI-sponsored infrastructure designed to safely and expeditiously evaluate new agents that are considered to have the greatest promise for adults with brain tumors.

This Limited Competition RFA is soliciting a single application from the current adult brain tumor consortia awardees, NABTT and NABTC. Solicitation via a limited competition was chosen because of the extensive time and resources that have been expended to create the current infrastructure. To develop a similar infrastructure de novo would be costly and would significantly reduce the pace with which innovative clinical trials could be initiated and completed.

Objectives and Scope

The overarching goal for the Consortium is to develop more effective therapies for adult brain tumors than those presently available. The overall objectives for the coming 5-year funding period are:

Consolidation of NABTT and NABTC into a single Consortium. In this FOA, the two currently funded adult brain tumor consortia, NABTT and NABTC, are asked to combine their efforts and consolidate infrastructure in order to maximize clinical trial efficiency and enhance support for translational research. It is envisaged that this organizational consolidation will still allow for the majority of the Consortium participating institutions (member sites) of both current consortia to be retained. In this way, the reformed Consortium will be able to capitalize on the scientific expertise and experience that has been nurtured during the previous award periods.

To ensure program continuity, this FOA allows for multiple PIs. It is encouraged that current awardees designate two PIs (i.e., one from each of the currently funded Consortia) who would serve jointly as lead PIs for this single consortium. The lead PIs are expected to be jointly in charge of the integrated Consortium Operations Center and Statistics and Data Center and serve as co-chairs of the Consortium Steering Committee.

If appropriate and desirable, leaders of individual member sites may be designated as PIs in the application. All the member sites, however, will be funded through subcontractual arrangements with the primary awardee. Also, the Consortium will have to implement procedures for ongoing site evaluation and retention of only well performing member sites.

Coordination of the Consolidated Consortium. The proposed consolidated Consortium must have an integrated coordination structure consisting of Operations Center and Statistics and Data Center. The Operations Center will be responsible for preparing clinical trial protocol documents, for arranging meetings for the Consortium, for assuring compliance with Food and Drug Administration (FDA) and Office for Human Research Protections (OHRP) regulatory and patient protection requirements, and for monitoring performance of institutional members of the Consortium. The Operations Center will also provide reports of the performance of the Consortium in meeting pre-specified time lines for Letter of Intent (LOI)/concept and clinical trial protocol development, for study implementation, for publication of Consortium studies, and for Member Institution performance. The Consortium must have prescribed procedures for addressing failure by investigators or institutions to meet these time lines. Statistics and Data Center will be responsible for all the statistical and the data management aspects of the Consortium. This center must ensure that clinical trials data are obtained directly from member institutions using a remote data entry (RDE) system. While the Consortium should select a single location for its Operations Center and Statistics and Data Center, it is permissible for key leadership staff (e.g., PIs, statisticians, pharmacists, and radiologists) to be located at remote sites as long as effective communication channels are maintained and the relationships and responsibilities of key staff are duly recognized and agreed upon by the grantee institution..

Member Institutions. The Consortium should include approximately 15 member institutions, a number that is deemed sufficient to complete approximately six Phase 2 studies and two or three Phase 1 studies per year, enrolling a total of approximately 250-300 patients per year. The candidate institutions must be selected based on their experience in developing and participating in Phase 1-2 trials, their ability to carefully monitor patients treated in the course of Phase 1-2 studies, their capabilities in reporting clinical data in a timely manner to the Statistics and Data Center (e.g., their data management infrastructure), their ability to contribute to the scientific leadership of the Consortium (e.g., in the areas of pharmacokinetics, pharmacogenetics, and pharmacodynamics research ), and their imaging capabilities. Institutions that are not Consortium members may participate (via a guest membership policy) in selected Consortium clinical trials if they have unique capabilities needed to complete a particular trial or if they have contributed significant scientific leadership in the development of a new agent under investigation.

If desirable, Consortium member sites may be divided into two groups to allow separate Phase 1 or 2 studies to proceed concurrently.

Laboratory and Imaging studies. Laboratory correlative studies (e.g., pharmacokinetic and pharmacodynamic studies) will be supported in part through the Biology/Pharmacokinetics-Pharmacodynamics Fund and through the Imaging Research Fund that the Consortium will establish and distribute to member institutions and laboratories. The Biology/Pharmacokinetics-Pharmacodynamics Fund will support the performance of the relevant laboratory testing using these specimens. The Consortium will establish a competitive process for soliciting and reviewing applications from researchers to perform additional studies on the collected specimens, specifically ancillary studies not part of the protocol’s original primary or secondary aims. The Consortium will be expected to obtain additional funds from other sources to supplement those provided in the Consortium award for the specimen resource and biologic studies.

The Consortium shall contract with VIEW (Virtual Imaging Evaluation Workspace), a network of NCI-funded Clinical Trials Cooperative Groups, to serve as the central image collection and archive center for selected studies that have novel imaging endpoints. The Consortium will develop the imaging research plan for the study and will then direct the interpretation and analysis of the archived images collected by VIEW to meet the imaging study objectives. Should VIEW not be able to meet the requirements of the Consortium for a particular study, the Consortium must seek other partners for collection and archiving of images.

Specific Objectives

Specific Objectives for the Program (which will be used as the evaluation criteria for the awardee if the award is made), include the following factors/benchmarks:

1) The number of Phase 1-2 clinical trials initiated and successfully completed (two or three and six per year, respectively, are expected);

2) The use of proper trial designs to determine appropriate doses in Phase 1 studies and appropriate endpoints in Phase 2 clinical trials;

3) The incorporation of adequate pharmacokinetic and pharmacodynamic studies into Consortium trials;

4) The incorporation of appropriate biomarkers to predict outcome and/or response to treatment, including the use of imaging studies for this purpose in Consortium trials;

5) The timely presentation of results at national meetings and timely publication of results in peer reviewed journals;

6) Timely clinical trials protocol development and activation (to meet timeline requirements defined by the NCI Cancer Therapy Evaluation Program, CTEP);

7) The generation of high quality data as evidenced by an effective quality control/quality assurance (QC/QA) program and by review of data submitted to CTEP; and

8) The number of clinical trial protocols/ancillary studies that result from SPOREs and/or Clinical Trials Cooperative Groups and clinical trial protocols/ancillary studies shared with SPOREs and/or Clinical Trials Cooperative Groups.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the NIH U01 cooperative agreement award mechanism.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

The NIH U01 mechanism is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator(s) retain(s) 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 Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

2. Funds Available

The total amount of funding that NCI expects to award through this announcement in FY 2009 is approximately $3.525 million. NINDS is co-funding this award at approximately $0.5 million in FY 2009, with their contribution restricted to funding of the necessary components to integrate imaging studies into Consortium clinical trials. The total commitment for 5 years of funding is approximately $18.072 million from NCI and approximately $2.5 million from NINDS. A single award is anticipated. An applicant may request a project period of up to 5 years, with the award period being from January 1, 2009, through December 31, 2014.

Facilities and administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

The eligibility to apply in response to this limited competition RFA is limited to the current recipients of the NABTT Operations (U01CA062475) and NABTC Operations (U01CA062399) Consortium Awards submitting jointly a single application.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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.

2. Cost Sharing or Matching

There is no cost sharing requirement for this RFA.

The most current 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

Not applicable.

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: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the 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 the application the ability to meet the RESEARCH OBJECTIVES of the FOA and to meet the investigator responsibilities described in Section VI.2.A Cooperative Agreement Terms and Conditions of Award. For the application submitted in response to this FOA, the standard PHS398 Research Plan (Sections A-D) is altered as follows:

Section 1: Progress Report. The application must include a progress report, which at a minimum addresses the following for both NABTT and NABTC:

Section 2: Consortium Consolidation and Investigators/Team Qualifications.

Section 3: Research Strategies and Research Plans. The research strategy and plans of the Consortium for developing new treatment approaches for adult brain tumors through Phase 1-2 studies must be described, including:

Section 4: Consortium Standard Operating Procedures for Clinical Trial Protocol Development. Describe the procedures developed and utilized by the Consortium to support the timely development of Phase 1-2 clinical trials. Specifically address the procedures listed below and describe indicators of success in their implementation:

Section 5: Consortium Standard Operating Procedures for Quality Assurance and Data Management and Analysis. The following should be addressed:

Section 6: Consortium Standard Operating Procedures for Regulatory Compliance: A description of the following should be provided:

Section 7: Member Institutions: The application should include a description of the following:

These materials count towards the 50-page limit.

Synopses of Member Institutions. The application should additionally provide a brief synopsis of how each Member Institution meets the criteria established by the Consortium for appropriate research capabilities and for acceptable performance (limited to two pages per Member Institution). These synopses do not count towards the overall 50-page limit for the Research Plan and may include, but are not limited to, the following:

Note on Budget: The budget for the Consortium must include the following broad categories:

Appendix Materials:

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. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

As mentioned above in the instructions for Sections 1 7, the following items are recommended for inclusion as the Appendix materials:

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: January 29, 2008
Application Receipt Date: February 29, 2008
Peer Review Date: June/July 2008
Council Review Date: October 2008
Earliest Anticipated Start Date: December, 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. The letter of intent should be sent to:

Jeffrey Abrams, M.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN Room 7025, MSC 7436
Bethesda, MD 20892 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-2522
Fax: (301) 402-0557
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 (U.S. Postal Service express or regular mail)
Bethesda, MD 20817 (for non-USPS delivery)

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 paper copies of the application and all copies of the appendix material in paper or pdf format must be sent to the address below:

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 non-USPS delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275

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 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 Principal Investigator 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.

6. Other Submission Requirements

Plan for Sharing Research Data

The applicant 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.

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, the application will:

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 Consortium will be able to meet its 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 1-2 studies for adult brain tumors using state-of-the-art research tools. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for the application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to moving a field forward.

The following general (NIH-wide) criteria appended with aspects specific to this FOA will be used. In addition to the general NIH-wide set of criteria, this FOA will use specific criteria as outlined below, to assess particular aspect specific to this FOA.

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?

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?

Specific to this FOA - Research Strategies and Research Plans:

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, and/or technologies for this area?

Specific to this FOA

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)?

Specific to this FOA:

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?

Additional Criteria Specific to this FOA:

Progress of the currently funded Consortia (NABTT and NABTC):

Clinical Trial Protocol Development:

Quality Assurance and Data Management and Analysis:

Regulatory Compliance:

Member Institutions:

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 and Minorities in Research: The adequacy of plans to include subjects from both genders and all racial and ethnic groups (and subgroups) 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).

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget 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 of the plan. 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. NCI will be responsible for monitoring the data sharing policy (see 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.

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

Not Applicable.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PIs will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in Item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for this program will be the cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

Throughout these Terms and Conditions of Award, Consortium refers to the organizational structure, which is composed of the Consortium lead PIs and other key personnel, the Operations Center, the Statistics and Data Center, and Member Institutions (i.e., member sites ) and site PIs, all of whom agree to collaborate on research goals of the Adult Brain Tumor Consortium.

2.A.1. The Awardee and Principal Investigator Rights and Responsibilities

The Consortium and its lead PIs will be responsible for developing the details of the clinical and laboratory research program, including definition of objectives and approaches, planning, implementation, analysis, interpretations and conclusions of studies, and publication of results. The Consortium will continue to develop Phase 1-2 clinical trial protocols in accord with the research interests, abilities and goals of the Consortium, and submit these protocols to CTEP for review and approval prior to their implementation. Specific Rights and Responsibilities for the Operations Center, Statistics and Data Center, Member Institutions, and the Imaging Center are described below.

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.

Operations Center and Statistics and Data Center Responsibilities:

The Operations Center and the Statistics and Data Center, under the oversight of the lead PIs, will be responsible for coordinating clinical trial protocol development, protocol submission for review and approval, study conduct (including central data collection and analysis), quality control including study monitoring and subsequent associated quality assurance, 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 Operations Center, with the guidance of the lead PIs and Steering Committee, will be responsible for development and maintenance of an organizational structure and Standard Operating Procedures for the Consortium.

2) Clinical Trial Protocol Development: It will be the responsibility of the Consortium 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 Operations Center will be responsible, in accordance with the Consortium’s SOPs, for the preparation and implementation of procedures for development and submission of Consortium clinical trial protocols to the CTEP Protocol and Information Office (PIO) in a timely fashion for review and approval by NCI.

a) Clinical trial protocols must be developed, submitted, and implemented in accordance with the DCTD Investigator's Handbook" (http://ctep.cancer.gov/handbook/index.html).

b) Submission of Consortium clinical trial protocols for review and approval by NCI must 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 Operations Center will be responsible for communicating the results of the CTEP Protocol Review Committee to relevant Consortium Committees and Consortium members.

d) The Consortium 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 NCI-sponsored investigational agents 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 Consortium’s SOPs must include timelines for the steps involved in the development of LOIs, Concept Proposals, and clinical trial protocols, and should include mechanisms for monitoring the performance of the Operations Center and Consortium members in meeting these time lines. The Consortium’s SOPs should also include corrective action plans outlining the steps to be taken when these time lines are not met. Data concerning the Consortium’s performance in meeting timelines for protocol development must be provided in the Annual Progress Report.

3) Study Monitoring: The Consortium must follow the general guidelines for study monitoring for CTEP-sponsored trials as described at http://ctep.info.nih.gov/monitoring/section2.html#2.2.2. The Consortium will be responsible for assuring accurate and timely monitoring of the progress of each study, and therefore must have standard procedures for timely data collection and data management consistent with the intensive data requirements and the need for rapid reporting necessary for Phase 1-2 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-defined accrual goals. If the Consortium wishes to continue accrual to a study beyond the total accrual goal for eligible and ineligible patients specified in the clinical trial protocol, the Consortium will have to obtain approval from CTEP prior to continuing patient accrual;

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) Ongoing assessment of patient eligibility and of disease measurability;

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 Member Institutions. These measures should include procedures for monitoring compliance with Consortium s guidelines for data timeliness on an institution and a study basis, including summary reports of data submission timeliness to be used for Institutional Performance Review and to be used for study monitoring (e.g., as specified by the Data and Safety Monitoring Plan)]. These summary reports should also be included in the Annual Progress Report;

f) Rapid reporting of treatment-related morbidity information and measures to ensure communication of this information to all relevant parties. For investigational agents sponsored by the NCI, this involves reporting to the Investigational Drug Branch (IDB), CTEP, via the Adverse Event Expedited Reporting System (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 semiannual reports for Consortium meeting agendas, and reports as required to comply with the Consortium’s Data and Safety Monitoring Plan; and

h) Adequate policies and procedures for closure of studies. If the Consortium wishes to close accrual to a study prior to meeting the initially established accrual goal, the interim results and other documentation should be made available to NCI staff for review and concurrence prior to implementation of the decision. It is recommended that statistical guidelines for early closure be presented as explicitly as possible in the clinical trial protocol in order to facilitate these decisions. In the event that the study is recommended for early closure for safety reasons, procedures in the Data and Safety Monitoring Plan regarding notification of CTEP must be followed.

4) Data Management Policies and Practices: The responsibilities of the Statistics and Data Center for data management related to study monitoring will 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 Health and Human Services (DHHS);

c) Implementing procedures for backing up the Consortium’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 NCI in a timely manner, upon the request of the Grants Management Officer, true copies of data files and supporting documentation for all NCI-supported protocols that have a major impact on patterns of care, as determined by the NCI.

5) Quality Control of Consortium Clinical Trials: Quality Control and Quality Assurance (QC/QA) Programs are inherently linked. The Clinical Trials Monitoring Branch (CTMB) of CTEP provides direct oversight of NCI-sponsored Consortia and Cooperative Group QC/QA programs. The Consortium will be 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 Consortium. Key items that must 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 Consortium trials;

ii) Timely and 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; and

v) Participation in Consortium administrative and scientific committees and/or other Consortium activities.

b) Procedures for placing Member Institutions on probation for inadequate performance and for removing such institutions from the Consortium if performance is not adequate during the probationary period or at any time that the institution (or participating site) does not meet Consortium standards for institutional performance.

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 CRAs in the Consortium’s data submission policies and ongoing training for all CRAs concerning changes to Consortium procedures and instructions for data submission in new protocols;

ii) Instruction for Study Chairs on their responsibilities for study monitoring;

iii) Instruction for Member Institution Principal Investigators and all members at participating sites on their responsibilities in complying with the Consortium’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., Office for Human Research Protections, 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 Consortium’s on-site monitoring program will be coordinated with the Clinical Trials Monitoring Branch (CTMB) and the Clinical Trials Monitoring Service (CTMS). On-site auditing of Consortium Member Institutions will occur approximately annually, with the timing of audits to be based in part on Member 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. The Operations Center and Statistics and Data Center will be responsible for providing the Clinical Trials Monitoring Service with the accrual and the protocol-specified data needed to conduct institutional audits. 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. The Operations Center and Statistics and Data Center will be responsible for coordinating development of and compliance with corrective programs in response to audits. In the event that the NCI determines that a Consortium Member Institution failed to adequately comply with NCI guidelines for conduct of clinical trials, the accrual of new patients to Consortium protocols at the affected institution shall be suspended immediately upon notice of the NCI determination. The suspension will remain in effect until the Consortium conducts the required audit and the audit report or remedial action is accepted by the NCI. The Operations Center will be responsible for notifying any affected participating institution of the suspension. During the suspension period, no funds from this award may be provided to the participating institution for new accruals, and no charges to the award for new accruals will be permitted.

6) Timely reporting of data to CTEP using the Clinical Data Update System (CDUS).

a) For most Consortium studies using CTEP IND agents, CDUS Complete reporting procedures will be used, which capture demographic, adverse event information (by course), and response data.

b) For clinical trials that do not use CTEP IND agents, reporting to CTEP will generally use the CDUS Abbreviated procedures (demographic data only).

7) Publications: Timely publication of major findings is central to the Consortium s mission and will serve as a primary means by which the Consortium s accomplishments will be evaluated.

a) The Consortium must have timelines for the development of abstracts for meeting presentations and manuscripts for submission for publication in scientific journals based on its clinical trials. In addition, mechanisms must be in place for monitoring the performance of the Consortium’s components in meeting these timelines. Corrective action plans must be implemented when these timelines are not met.

b) Publication and oral presentation of work conducted under the Consortium’s Cooperative Agreement requires appropriate acknowledgment of NCI support.

c) For investigations using an agent supplied under a CRADA or CTA, the NCI pharmaceutical collaborator will have an opportunity to review manuscript drafts prior to their submission for publication as per the NCI Standard Protocol Language for CRADAs and CTAs. The NCI will have access to all data generated under this cooperative agreement and may periodically review the data. The awardee will retain custody and primary rights to the data consistent with current DHHS, PHS, and NIH policies.

8) Consortium Meetings: The Operations Center will be responsible for the organization of semiannual meetings (or meetings scheduled at other times if approved by CTEP) to review the Consortium’s progress, establish priorities, and plan future activities. Additional meetings of Consortium members and meetings with NCI and NINDS 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 Operations Center and Statistics and Data Center will distribute the electronic and/or hard copies of the Report to Consortium members and NCI/NINDS program staff); and

d) Preparing summaries as appropriate after each meeting to be sent to Consortium members and NCI/NINDS program staff.

9) Consortium Communications: The Operations Center must establish routine electronic communication with Member Institutions to facilitate clinical trial protocol development and study monitoring and to facilitate the work of the Consortium’s Study and Scientific Committees. Relevant communication methods include web site postings, e-mail, teleconferences, and video conferences.

10) Compliance with Federal Regulations Concerning Clinical Research: The PIs and Operations Center will be responsible for ensuring that the Consortium complies with all applicable Federal regulations concerning the conduct of human subjects research. Policies and guidelines to be addressed include:

a) OHRP Assurances: The Operations Center must assure that each participating site has a current, approved assurance on file with OHRP.

b) IRB Review of Consortium Protocols: The Operations Center must assure that each Consortium clinical trial protocol is reviewed and approved by each Member 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 Operations Center must assure that each patient (or legal representative) gives written informed consent prior to entry on study.

d) IRB Review of the Operations Center and Statistics and Data Center (http://www.hhs.gov/ohrp/humansubjects/assurance/engage.htm): An IRB should determine and document that the Operations Center and Statistics and Data Center have sufficient mechanisms in place to ensure that: (i) management, data analysis, and Data Safety and Monitoring (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) informed consent is obtained from each subject in compliance with DHHS regulations.

e) Registration of Consortium Investigators: The Operations Center will be responsible for assuring that Consortium investigators performing trials involving DCTD Investigational Agents are NCI-registered investigators (Form 1572).

f) Adverse Event Reporting: The Operations Center will be responsible for assuring timely reporting of all serious and/or unexpected adverse events. Adverse events must be reported using the Common Terminology Criteria for Adverse Events (CTCAE), 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 the NCI, this procedure involves reporting to the Investigational Drug Branch (IDB), CTEP, via the Adverse Event Expedited Reporting System (AdEERS) according to CTEP guidelines specified in each clinical trial protocol (http://ctep.info.nih.gov/reporting/adeers.html).

g) Assuring that the Consortium is in compliance with CTEP requirements described in the DCTD Investigators' Handbook for storage and accounting for investigational agents (including NCI/DHHS Drug Accountability Records [DAR] procedures), and is in compliance with FDA requirements for investigational agents.

11) 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.

12) The Operations Center will be 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 must comply with the general policies of the NCI, NINDS and the NIH.

13) Fiscal management of the Consortium, including:

a) Establishment of consortium arrangements with Member Institutions to support Consortium-related activities at each Member Institution;

b) Administration of the Biology/Pharmacokinetics Fund, including the process for selecting laboratories to perform specific studies (a competitive process is encouraged when feasible); amd

c) Distribution of funds from the Site Support and Imaging Study Support Funds to member institutions to support clinical research costs for patients accrued onto Consortium 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 Consortium protocol, the capitation formula for institutional reimbursement required to offset specific research expenses will be reviewed and approved by the lead PIs and Steering Committee in coordination with the Operations Management team.

14) Submission of annual progress reports to the NCI/NINDS that describe activities and accomplishments during the previous year of the Consortium. The report will use the PHS 2590 form and include:

a) A summary of the overall performance of the Operations Center and Statistics and Data Center in meeting their responsibilities to the Consortium for clinical trial protocol development, study monitoring, and complying with Federal regulations;

b) Summary data on performance of each Consortium Member 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.

15) Procedures to allow non-Consortium institutions to participate in the development and conduct of Consortium trials in those limited situations in which an institution has distinctive expertise or capabilities that would contribute to successful conduct of a Consortium study.

Member Institution Responsibilities:

1) Participation of Member Institution investigators in Consortium activities shall involve the following:

a) Offering eligible patients participation in Consortium studies and entering sufficient patients to meet accrual targets;

b) Participating in research design and clinical trial protocol development, including:

i) Serving as clinical trial protocol Chairs or as members of protocol study teams;

ii) Participating in the Scientific and Administrative Committees needed to support the Consortium’s research objectives;

c) Participation in meetings: Appropriately participating in the semiannual meetings of the Consortium (and in other meetings as deemed necessary for performance of Consortium activities);

d) Following the Consortium’s SOPs for the conduct of clinical research.

2) Implementing the core data collection method and strategy of the Consortium: It is the responsibility of each Member Institution to ensure that the procedures for data submission for each Consortium 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 Center.

3) Complying with mechanisms for quality assurance and quality control of therapeutic and diagnostic modalities employed in Consortium 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) Imaging: Submission of appropriate imaging studies to allow central review of claimed responses and adequacy of imaging and to allow the imaging research objectives of the Consortium to be met.

4) On-site Auditing: Participation in the on-site monitoring program established by the Consortium.

5) Human Subjects Protection: Each institution must comply with OHRP and FDA regulations concerning protection of human subjects. Member Institutions must implement the procedures established by the Consortium to meet OHRP and FDA requirements for the protection of human subjects.

6) Adverse Event Reporting: Implementing the procedures established by the Consortium for assuring timely reporting of all serious and/or unexpected adverse events.

7) Investigational agent responsibilities: Implementing the procedures established by the Consortium for assuring that Consortium investigators performing trials involving DCTD Investigational Agents are NCI registered investigators (Form 1572) and for assuring that the Consortium complies with CTEP requirements described in the DCTD Investigators' Handbook for storage and accounting for investigational agents (including NCI/DHHS 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 Consortium Steering Committee will establish a process for the selection of the laboratories to perform these studies. These projects may be supported using the Biology/Pharmacokinetics Funds of the Consortium or by independent funding.

10) Participating in Consortium procedures for the timely publication of major findings.

11) Conflict of Interest: Complying with the Conflict of Interest Policy of the Consortium to ensure that there is no reasonable expectation that the design, conduct, or reporting of research conducted by the Consortium will be biased by any conflicting financial interest of an investigator.

Imaging Study Research responsibilities include participation of the Imaging Chair(s) in Consortium activities, as demonstrated by the following:

1) Developing a correlative imaging research program, in collaboration with other Consortium investigators, that directly contributes to the Consortium’s ability to incorporate imaging endpoints into its overall clinical research program. Identifying evolving novel imaging technologies that can be incorporated into planned or future clinical trials within the consortium.

2) Participating in the development of clinical trial protocols, particularly for imaging components.

3) Developing the contract with VIEW (or other contractors) to acquire, collect, and archive medical images for the imaging studies when appropriate.

4) Guiding and participating in the analyses of the imaging data.

5) Participating in the Scientific and Administrative Committees needed to support the Consortium’s research objectives.

6) Participation in meetings: Appropriately participating in the semiannual meetings of the Consortium (and in other meetings as deemed necessary for performance of Consortium activities). Attendance at other NIH-supported conferences or workshops on neuro-imaging is also expected to encourage interaction and coordination with other neuro-imaging networks to further advance technical and/or informatics approaches.

7) Human Subjects Protection: It is anticipated that the Imaging reviews will most often be retrospective without patient identifiers. However, as applicable, the Consortium must be in compliance with OHRP and FDA regulations concerning protection of human subjects.

8) Participating in Consortium procedures for the timely publication of major findings.

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

2.A.2. NIH Responsibilities

The NCI and NINDS will coordinate and facilitate various activities of the Consortium. The NCI and NINDS staff members will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The NCI Program Director serving as Project Scientist will be the main NCI contact for all facets of the scientific interaction with the awardees and will provide oversight and advice to the awardee on specific scientific and/or analytic issues in addition to programmatic issues. The NINDS Program Director serving as Project Coordinator will provide oversight, advice, and coordination of efforts pertinent to neuro-imaging. The NCI Project Scientist and the NINDS Project Coordinator will serve as members of the Consortium Advisory Committee. Additional NCI and NINDS staff members may also be involved as needed (for example, by acting as Collaborators or Coordinators).

Specific responsibilities of NIH Program Staff will include the following:

1) Monitoring Consortium progress. Actions necessary for monitoring may include, but are not limited to, the following: regular communications with the PIs and staff members, periodic site visits for discussions with awardee research teams, response audits to confirm activity reported from a Consortium clinical trial, observation of field data collection and management techniques, fiscal review, review of clinical trial reports submitted by the Consortium to NCI, review of the Consortium’s annual progress report, and attendance at Consortium meetings. The NCI retains, as an option, the right to conduct periodic external reviews of progress.

2) Scientific Liaison: Serving as a resource with respect to other ongoing NCI and NINDS activities that may be relevant to the Consortium research efforts to identify promising new leads, to facilitate compatibility with other NCI and NINDS research projects, and to avoid unnecessary duplication of effort.

3) CTEP Assistance in Clinical Trial Protocol Development: The clinical trial protocol must be a detailed written plan of a clinical experiment mutually acceptable to the Consortium 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 Letter of Intent (LOI) from the Consortium declaring interest in conducting a particular study. The PRC will formally review the LOI. Following review, the NCI Project Scientist will provide a Program response to the Consortium 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 NCI 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 Trial Protocols: All Consortium protocols, including protocols utilizing agents not sponsored by NCI, 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 will provide the Consortium 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) the strength of the scientific rationale supporting the study;

b) the clinical importance of the question being posed;

c) the avoidance of unnecessary duplication with other ongoing studies;

d) the appropriateness of study design;

e) consistency with development plans for particular IND agents;

f) a 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) methods of monitoring and reporting to NCI to be used.

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 Consortium 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 protocol that it has not approved. The NCI Project Scientist will be available to assist the Consortium in developing a mutually acceptable protocol, consistent with the research interests, abilities, and strategic plans of the Consortium 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 Involvement in Auditing of Member Institutions: The Clinical Trials Monitoring Branch of CTEP will coordinate with the Consortium the performance of on-site audits at Consortium Member Institutions, which are to occur at approximately 2-3 year intervals. The Clinical Trials Monitoring Branch will review audit results and the corrective plans developed by the Consortium in response to the audits.

7) CTEP Involvement in Imaging Research: The NCI Imaging Research Coordinator will advise the Consortium Steering Committee (through the NCI Project Scientist) 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 Consortium protocols with imaging components and will assist the NCI Project Scientist and the NINDS Project Coordinator in the overall review of Consortium imaging research activities and accomplishments.

8) CTEP Involvement in Radiation Oncology Research: The NCI Radiation Oncology Research Coordinator will advise the Consortium Steering Committee with respect to ongoing NCI activities and research opportunities related to radiation therapy for brain cancers. He/she will participate in CTEP review of Consortium protocols with radiation therapy components and will assist the NCI Project Scientist in the overall review of Consortium radiation oncology research activities and accomplishments.

9) CTEP Involvement in Clinical Trial Protocol Closure: Protocol closure is primarily the responsibility of the Consortium and the specific Protocol Committee. The NCI Project Scientist 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: NCI Biometrics Research Staff members will review mechanisms established by the Consortium for data management and analysis. When deemed appropriate, staff members 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 Plan: The NCI Program Director, assisted by the Biostatistical Research Branch (BRB) staff, will assess Consortium compliance with NCI and NIH established policies on Data and Safety Monitoring Plans. The NCI Project Scientist must review and approve the Consortium s Data and Safety Monitoring Plan. One or more CTEP staff will serve as non-voting members on the Consortium’s Data and Safety Monitoring Committee (DSMC), should the Data and Safety Monitoring Plan (DSMP) specify a DSMC.

12) Consortium Meetings: The NCI Program Official and Project Scientist as well as the NINDS Project Coordinator will attend semiannual Consortium meetings to discuss relevant scientific information, progress in the clinical trials, and the status of newly available investigational agents and other research opportunities in order to plan future activities. Other NCI staff members (e.g., from the Investigational Drug Branch, Radiation Research Program, and Diagnostic Imaging Program) or NINDS staff will attend as needed.

13) CTEP Involvement in Investigational New Drug Applications: The NCI Program Official and Project Scientist, assisted by the Chief, Regulatory Affairs Branch (RAB), CTEP, will advise investigators of specific requirements and changes in requirements concerning IND sponsorship that the FDA may mandate. Investigators performing trials under cooperative agreements will be expected, in cooperation with the NCI, to comply with all FDA monitoring and reporting requirements for investigational agents.

14) CTEP Review of Federally Mandated Regulatory Requirements: The Chief, Clinical Trial Monitoring Branch (CTMB), through the NCI Program Director and Project Scientist, will advise the Consortium regarding mechanisms to meet FDA regulatory requirements for studies involving DCTD-sponsored investigational agents and OHRP requirements for the protection of human subjects by Consortium 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 the NCI as an IND agent sponsor. Data from studies of non-NCI-sponsored agents must be available for external monitoring as described in the policies and procedures established by the Consortium for on-site auditing of clinical trials data. 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 Industry Sponsor will have complete access to the data for any and all regulatory filings.

16) Access to Agents for Pre-Clinical Testing: For NCI-sponsored IND agents, NCI will facilitate transfer of material to investigators with a Materials Transfer Agreement (MTA).

17) CTEP Review of Progress: Performance of the Consortium will be reviewed at least annually by the NCI Project Scientist and 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 Consortium’s 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.

The NCI Project Scientist and the NINDS Project Coordinator as well as other NIH staff members acting as Collaborators or Coordinators will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is essential, the NCI Project Scientist will seek NCI waiver according to the NCI procedures for management of conflict of interest if such participation is deemed necessary. The NINDS Project Coordinator will seek analogous waiver.

Additionally, an NCI program director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NCI Program Official and Project Scientist may be the same person. In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NCI waiver as stated above.

2.A.3. Collaborative Responsibilities

The Consortium will have a Steering Committee as a governing body. Steering Committee will consist of the following voting members: Consortium lead PIs who will serve as Committee co-chairs, representatives of the Member Institutions (one per site, e.g. site PIs), director of the Operations Center and director of the Statistics and Data Center and a patient representative. Each member of the Steering Committee will have one vote. The NCI Project Scientist and the NINDS Project Coordinator as well as additional NIH representatives may participate as advisors and observers in the Steering Committee meetings as needed but will not have voting rights.

The Steering Committee will be responsible for the approval of any changes to the Consortium organizational structure and Consortium Standard Operating Procedures. The Steering Committee will have primary responsibility to establish priorities, and to develop and provide preliminary approval of protocols (prior to submission to NCI and final NCI approval), and to review progress. The Steering Committee will be responsible for reviewing on a regular basis the performance of the Operations Center and Statistics and Data Center and the performance of the ancillary scientific activities (imaging, pharmacology, and biologic studies). The Steering Committee and the lead PIs will be responsible for assuring that deficiencies identified during these reviews are adequately addressed in a timely manner. The Steering Committee will be responsible for reviewing Member Institutions for adequate performance, and will have the authority to place on probation and to suspend Member Institutions as well as to add new institutions to replace any Institutions whose membership in the Consortium is suspended. The Steering Committee will also establish a process for the selection of the laboratories to perform laboratory studies associated with individual clinical trial protocols. Steering Committee will authorize the spending of funds from the Biology/Pharmacokinetics Fund and the Imaging Research Fund.

In addition to the Steering Committee, the Consortium will have an Advisory Committee to include the following members:

The Advisory Committee must meet at least twice per year, with at least one of the meetings being in person. The Advisory Committee should assist the Steering Committee in reviewing Consortium overall research plan and strategic goals. At a minimum, the Advisory Committee should review all Consortium clinical trials protocols that are pending CTEP approval and should advise the Consortium regarding gaps/opportunities in their portfolio of studies. Additionally, the Advisory Committee should discuss potential collaborations between the Consortium and SPOREs, as well as other NCI or NINDS-sponsored clinical trials, translational research, or neuro-imaging groups.

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 composed of three members will be convened to review the CTEP decision and recommend an appropriate course of action to the Director, DCTD. It will have three members: a designee of the Steering Committee chosen without NCI staff voting; one NCI designee; and a third designee with expertise in the relevant area who is chosen by the other two. In the case of individual disagreement, the first member may be chosen by the individual awardee. This special 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 DHHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590, annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement. A suggested format for Consortium-specific information relevant to the progress summary section of the Form PHS 2590 will be provided. Performance of the Consortium in developing new LOIs and clinical trial protocols should be discussed, as should the performance of Member Institutions participating in Consortium 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 provided in the progress summary. 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 Consortium semiannual meeting and shall include specific data on patient/participant accrual as well as detailed reports of treatment-associated morbidity. Quarterly accrual reports must be provided as appropriate to CTEP for all active trials through the NCI s Instructions and Guidelines for CDUS reporting are at http://cancer.gov/reporting/cdus.html.

Section VII. Agency Contacts

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:

NCI Contact:

Jeffrey Abrams, M.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN Room 7025, MSC 7436
Bethesda, MD 20892-7436 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-2522
Fax: (301) 402-0557
Email: [email protected]

NINDS Contact:

Jane W. Fountain, Ph.D.
Program Director
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2110, MSC 9521
Bethesda, MD 20892-9521 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-496-1431
FAX: 301-402-2060
Email: [email protected]

2. Peer Review Contacts:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service Express or regular mail)
Rockville MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
Fax: (301) 402-0275
Email: [email protected]

3. Financial or Grants Management Contacts:

Eileen M. Natoli
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPS, Room 243, MSC 7150.
Bethesda, MD 20892-7150 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-8791
Fax: (301) 496-8601
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

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.htm. 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.

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://escr.nih.gov). 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://www.nihms.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 RFA 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 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 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. The NIH Grants Policy Statement can be found at 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


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