and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
National Center for Research Resources (NCRR), (http://www.ncrr.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), (http://www.niddk.nih.gov)
Title: Human Pancreatic Islet Cell Resources (ICRs)
Announcement Type
This is a modification of RFA-RR-01-002 that was previously released January 3, 2001.
Request For Applications (RFA) Number: RFA-RR-05-003
Catalog of Federal Domestic Assistance Number(s)
93.389, 93.847
Key Dates
Release Date: July 18, 2005
Letters of Intent Receipt Date(s): December 6, 2005
Application Receipt Dates(s): January 6, 2006
Peer Review Date(s): February-March 2006
Council Review Date(s): May 19, 2006
Earliest Anticipated Start Date: July 1, 2006
Expiration Date: January 7, 2006
Due Dates for E.O. 12372
Not Applicable
Additional Overview Content
Executive Summary
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, 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
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
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 Announcement1. Research Objectives
Patients afflicted with Type I diabetes mellitus have achieved long-term freedom from exogenous insulin and hypoglycemic attacks after having received human pancreatic islet cell transplants. To facilitate the development of islet transplantation for the treatment and cure of Type 1 diabetes, the National Center for Research Resources (NCRR), together with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Juvenile Diabetes Research Foundation International (JDRFI), established the Islet Cell Resource (ICR) Center program to isolate, purify, characterize and distribute human pancreatic islet cells for both transplantation into diabetic patients and use in laboratory studies.
Background
Diabetes mellitus affects approximately 18 million people in the United States. Individuals with Type I diabetes have lost their ability to generate sufficient amounts of insulin due to autoimmune destruction of the insulin-producing beta cells that are grouped with other types of secretory cells within the islets of Langerhans of the pancreas.
While injection of exogenous insulin continues to be the standard treatment for patients with Type I diabetes, transplantation of human islet cells may be an alternative. Patients afflicted with Type I diabetes mellitus have achieved long-term independence from exogenous insulin and absence of hypoglycemic attacks after having received human pancreatic islet cell transplants. However, the recovery of functional pancreatic islets from cadaveric donor pancreata is a complex procedure and needs to be optimized.
Several aspects of the islet transplantation process may be critical: the clinical status of the donor before removal of the pancreas, surgical procedures involved in its excision, the enzymatic dispersal of the pancreatic components, culture of the islets after dispersal, the transplantation procedure and the recipient's immunosuppression remain to be optimized.
Selection of appropriate recipients for islet transplantation requires characterization of this population with particular attention to their response to insulin therapy. Reports from the Diabetes Control and Complications Trial (DCCT) suggest that intensive treatment regimens that achieve tight control of blood glucose can significantly reduce the onset and progression of resultant complications in individuals with Type I diabetes. However, some diabetic patients who practice such tight control experience lability of blood glucose levels in response to changes in health status, diet, exercise, or insulin dose. Because even small changes in their daily regimen may interfere with glucose control, these diabetic patients are said to be "brittle". For this subpopulation, insulin therapy is life saving, but may lead to frequent adverse events such as severe hypoglycemia. Islet cell transplantation could provide significant benefits to diabetics for whom effective regulation by insulin therapy is difficult. In addition, those patients who receive immune suppression in association with kidney transplantation may also have a favorable risk-benefit profile for islet transplantation.
The objectives of this RFA are to:
ICR applicants should describe collaborations, or plans to establish collaborations, with clinical programs that have experience in transplanting human islet cells and wish to optimize such protocols. It must be emphasized that awards resulting from this RFA are not intended to provide financial support for either clinical transplantation protocols or patient care.
The ICR applicant's research plan should include proposals to:
The Administrative and Bioinformatics Coordinating Center (ABCC) has been established to 1) be responsible for the organization and conduct of ICR Steering Committee meetings whose agendas include protocol review and evaluation of progress; 2) collect data, organize and analyze the methods and assays used to produce islet cells and correlate these data with post-transplant islet cell function; 3) correlate clinical trial data such as patient and donor demographics and baseline assessments, and relevant laboratory and clinical data that result from the use of the islets generated. The ABCC will maintain the database into which all ICRs and collaborating institutions will deposit their data for subsequent analysis. The applicant organization should describe its proposed interaction with the ABCC.
The research plan should follow the instructions in the PHS 398 application form (rev. 4/98, http://grants.nih.gov/grants/forms.htm).
Program Structure
Each ICR should be an identifiable organizational unit formed either within a single institution or with a collaborating institution(s). The expertise and technologies relevant to this RFA should reside within the ICR, providing a multidisciplinary structure that can coordinate activities between basic science investigators and clinicians to translate basic research discoveries into clinical applications. The ICR will facilitate research by providing both laboratory-based and clinical investigators with access to technology and equipment needed for islet cell research that lead to implementation of practical transplantation protocols. These may include current Good Manufacturing Practice (cGMP) suites, Good Laboratory Practice (GLP) isolation procedures, microarray technology, and cell sorters. Applicants must have demonstrated significant research expertise in islet cell isolation and have facilities within its institution that would enhance its productivity. While each ICR may not have a Training Program specifically designed to advance islet cell transplantation therapy, the institution may wish to use this opportunity to educate other investigators about relevant scientific and ethical issues.
The ABCC serves the administrative functions common to the ICRs, houses the bioinformatics core, maintains the consolidated database, provides administrative oversight of the Steering Committee and coordinates ICR activities such as complex assays and unique technologies that would best be housed in a generally accessible, single core, as well as sharing of islets, enzymes and other agents.
A Steering Committee will be responsible for scientific oversight and development of collaborative interactions among the ICRs, an example of such being shared research on islet cell isolation procedures.
A representative and an alternate from each ICR must be designated to serve on the Steering Committee and must recuse themselves from discussion of any application submitted by individuals affiliated with their home institution.
Each ICR must agree to provide pancreatic islets only to investigators whose protocols, either basic or clinical, have received favorable review by the Steering Committee and/or the ABCC and comply with the current goals of the Funding Entities.
Applicants are strongly encouraged to identify a clinical research program within their institution to facilitate islet cell transplantation. The clinical facility personnel should help to maintain quality assurance and compliance of the various aspects of the protocols.
Specialized Resource Facilities and Services
Advanced resources are required to develop pre-clinical data and implement clinical studies on cell therapies. Applicants should document the availability of existing laboratories, unique assays, cell preparation facilities and quantification of existing islet isolation activity. Clinical activities, either within the applicant's own institution or collaborating institution(s) that would to assist the awardee in achieving the goals outlined within this RFA should also be described. A favorable review of an application responding to this RFA must not be interpreted as an approval of any accompanying clinical transplantation protocol.
Each ICR application must include a description of all the proposed core components of the types cited above, and how they would relate to the ICR and other awardees. For those applications that are in the funding range, a committee of representatives from the Funding Entities will determine which will be selected as common cores to avoid unnecessary duplication of effort among all the ICRs. NIH-supported investigators from both within and outside of the ICRs would be eligible to submit a request for a service that any of the ICR cores provide. The Steering Committee would review the requests based on their scientific merit. Subsequently, the Funding Entities would consider these requests with regard to the scientific review, program relevance and availability of funds and set priorities based on these factors. Funds would be awarded to the core facility to offset the cost of these common services.
An ICR application should, at minimum, address:
See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.
Section II. Award Information1. Mechanism(s) of Support
This funding opportunity will use the U42 award mechanism(s).
As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.
This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.
The NIH U42 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".
Although the financial plans of the NCRR and NIDDK, hereafter termed Funding Entities, provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of applications of appropriate scientific and technical merit. Designated funding levels are subject to change at any time prior to final award, due to unforeseen budgetary, administrative, or scientific developments. It is not known if new or competing renewal applications will be accepted or if this RFA will be reissued.
2. Funds Available
NCRR and NIDDK intend to commit approximately $8 million in Fiscal Year 2006 to fund 6-8 new and/or competing continuation grants in response to this RFA. An applicant may request a project period of up to 3 years and a budget for direct costs up to $775,000 dollars per year.
Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
Provision of additional financial support may be considered, based on the productivity and needs of the awardee. The anticipated start date for these awards is July 1, 2006.
Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.
Section III. Eligibility Information1. Eligible Applicants
1.A. Eligible Institutions
You may be party to and submit (an) application(s) if your organization has any of the following characteristics:
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 of an ICR center. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.
2. Cost Sharing or Matching
Cost sharing is not required.
3. Other-Special Eligibility Criteria
The applicant must be willing to commit to fully and openly share data with other members of the ICR consortium.
An eligible institution may be party to multiple applications. However, it may be the applicant institution on only one application.
Applications for renewal of existing projects are eligible to compete with applications for new awards.
Section IV. Application and Submission Information1. 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 most current PHS 398 research grant application instructions and forms. Applications must have a Dun & Bradstreet (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.
3. Submission Dates and Times
Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.
3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date(s): December 6, 2005
Application Receipt Dates(s): January 6, 2006
Peer Review Date(s): February-March 2006
Council Review Date(s): May 19, 2006
Earliest Anticipated Start Date: July 1, 2006
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 IC 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.
Sheryl Brining, Ph.D.
Director, Office of Review
National Center for Research Resources
Democracy Plaza One, Room 1074
6701 Democracy Blvd.
Bethesda, MD 20892
Telephone: (301) 435-0809
FAX: (301) 480-3660
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 express/courier service; non-USPS service)
Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).
At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:
Sheryl Brining, Ph.D.
Director, Office of Review
National Center for Research Resources
Democracy Plaza One, Room 1074
6701 Democracy Blvd. Bethesda, MD 20892
Telephone: (301) 435-0809
FAX: (301) 480-3660
Email: [email protected]
Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.
3.C. Application Processing
Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NCRR. 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.
Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.
4. Intergovernmental Review
This initiative is not subject to intergovernmental review.
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 NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.
6. Other Submission Requirements
Material to Include in the ICR Application
An application to establish or re-compete an ICR should be submitted by the proposed Director who will be responsible for organizing and maintaining the ICR research program. A clear description of the plans for communication, interaction, collaboration and sharing among investigators within and between each ICR should be included. Each proposed ICR Director should also propose procedures for handling day-to-day issues, both administrative and scientific. The ICR Director should have the responsibility for oversight and coordination of all projects or components involving that ICR, whether or not they occur at his/her institution. Support for at least 0.25 FTE will be provided for the position of ICR Director. Provision will be made for partial support for a qualified investigator(s) to assist in the direction of the ICR and additional support for individuals to perform technical procedures. The application should detail how this would be accomplished through the inclusion of diabetologists, transplant surgeons and immunologists who are active in clinical research.
The ICR application should provide and justify an estimate of the cost of producing islets cell per transplant recipient and per basic research protocol. In addition, each ICR must describe any clinical core either at its own institution or collaborating institution that would participate with the ICR in islet cell transplant projects. Each application must also describe the institutional oversight procedures to be employed and must clearly outline the proposed administrative and organizational structure of their ICR, including integration, collaborative arrangements, and roles for key investigators from all institutions involved with the ICR. The applicant must also state willingness to participate in the Steering Committee that will integrate the activities of the ICRs and agree to abide by its governance.
Description of Proposed Resources
Applicants to this RFA should consider the points below as examples of relevant information to include in the application. These are examples only and should not be construed as being required or limiting. Applicants are encouraged to address these and/or other points pertinent to the objectives of the RFA.
Pancreas Harvesting
Describe the existing physical facility for isolation and assay of islet cells and the operational guidelines under which GLP is assured and islet cells are produced under cGMP conditions.
Describe plans for procurement of pancreata, including any relevant contracts, consortia agreements and cost estimates. Estimate the number of pancreata available to the proposed ICR annually for islet isolation. This would include all sources, including local transplantation networks. The basis upon which this estimate is made should be documented and presented and accompanied by letters of agreement from the organizations and institutions that will provide pancreata to the ICR. If transplantation of whole pancreata is performed at the applicant's institution, cite the number of whole pancreata that have been transplanted annually for the past five years. Describe the rationale employed when deciding whether the providing organization will allocate a pancreas to either a whole organ transplantation or islet cell transplantation protocol.
Recommend inclusion and exclusion criteria for pancreas donors and pancreata that will be used for islet cell transplantation. Describe the clinical setting with suggested physiological and pharmaceutical interventions to maintain the donors until excision of the pancreas has been completed.
Describe any plan to seek donors having unique characteristics that could yield information that would be relevant to islet characteristics and transplantation success.
Estimate the cost and identify the funding source(s) in place to obtain each pancreas. Provide an estimate of the number of pancreata that must be harvested to fully transplant one recipient.
Islet Isolation
Describe in detail the method planned to isolate islets from whole human pancreata.
Describe quality control (QC) and quality assurance (QA) provisions made at interim points in the procedure and for the final product. o Describe plans to optimize the isolation of islets for clinical and basic research.
To comply with the intent of cGMP, isolation of islet cells should follow a set of current, scientifically sound methods, practices or principles that are implemented and documented during product development and production to ensure the consistent production of islet cells that can be administered safely and with consistent purity and functional capacity. Describe elements of cGMP that would be used in the isolation of islet cells, such as: a) facility design to control operations; b) adequate documentation/records; c) production and process controls; d) quality control/assurance; e) validation; f) equipment and reagents that are calibrated/qualified; g) personnel that are trained and certified; h) traceability; and i) environmental monitoring. It is expected that each ICR will be capable of FDA certification for cGMP, initially to support Phase I trials, and subsequently, Phase II clinical trials. Provide evidence of such compliance that has been documented by an outside organization that is qualified to evaluate cGMP facilities.
Describe final product specifications for islet cell preparations, such as: a) presence of non-islet cells; b) absence of infectious agents; c) sterility; d) ATP content; e) oxygen consumption rate; f) specific cell markers. Describe the specifications that will certify that islet cells are suitable for use by investigators at a recipient institution.
Cite QC and QA assay measurements obtained from prior islet cell isolations. Describe the entire experience and dates thereof of the proposed facility and personnel in providing islets for clinical transplantation protocols. Describe the clinical outcome of those transplantations. Describe the experience in providing equally qualified islets to basic researchers.
List the clinical measurements and end points used to determine islet cell functionality if they were transplanted into animals or humans. Describe variations in isolation technique that are known to affect islet cell sterility, viability or function.
Describe measures to maintain sterility, viability, and function of islet cells that are to be distributed to investigators at both ICR and non-ICR locations.
Provide the research study plans through which the harvesting and maintenance of human islet cells will be optimized for in support of clinical and basic research protocols.
Describe existing and planned assays that are or will be employed to determine the number, purity and functionality of the islets.
Describe the experience of the proposed ICR in developing and implementing tests that are predictive of clinical efficacy.
Islet Distribution
Propose how the Steering Committee should prioritize investigators' requests for islet cells, for both clinical and basic research protocols, and how islet cells should be allocated between ICR and non-ICR institutions, acknowledging that the Steering Committee will establish the procedures employed.
Describe research plans to optimize shipping of islets to sites outside of the ICR institution.
Transplantation
Describe the location of the ICR relative to the location of the on-site transplantation facilities.
Cite prior local experience or collaborations with other investigators in the transplantation of islet cells. If the applicant has had no prior experience with islet transplantation, an investigator at the applicant's institution with experience in the field should be named, with a letter describing that experience, proposed contribution and intention to collaborate with the ICR on protocols involving islet cell transplantation.
Define the inclusion and exclusion criteria for type 1 diabetic candidates for islet cell transplantation. o Describe pre-transplant medical testing and follow-up of diabetic patients that are eligible for islet cell transplantation. Identify the funding source(s) to support these tests.
Propose the process by which islet cells are received, held for and infused into the recipient.
Describe the tests to assess the function of the transplanted islets and present a data analysis plan to compare pre-transplant and post-transplant test results. Identify the source of funds to support such follow up.
Research support
Interaction with the ABCC
Describe the means by which basic laboratory and clinical data will be acquired and transmitted to the ABCC in a timely manner.
Describe the process by which the proposed ICR will coordinate its activities with those of all other ICRs and those of the Steering Committee. Include the administrative, supervisory, and collaborative arrangements for achieving the goals of the program, and a willingness to cooperate with the ICRs and Funding Entities.
Describe how assay and disbursement data will be tracked for each lot of islet cells.
Outline the procedure to collate and analyze data from ongoing clinical and basic research studies that have either been approved by the Steering Committee or use ICR resources.
Provide a description interaction with ABCC support for analysis of protocol design and statistical evaluation of planned and completed protocols.
Describe the plan to interact with the DSMB responsible for oversight of the clinical protocols that utilize ICR resources.
Detail how privacy and security of all patient information as well as access by controlled authorization will be ensured.
Since human somatic cell transplantation involves the administration of materials of biological products, it is regulated by the Center for Biologics Evaluation and Research (CBER), FDA. IND applications are filed concerning clinical use of such products. Respondents to this RFA should convey their familiarity with such requirements for clinical, pre-clinical and animal studies.
CBER has prepared documents relevant to this RFA that include:
Information on Submitting an Investigational New Drug Application, including cGMP and GLP, for a Biological Product available at:
http://www.fda.gov/cber/ind/ind.htm.
Pancreatic Islet Specific Documents
Dear Colleague Letter to Transplant Centers: Allogeneic Pancreatic Islets for Transplantation (9/2000) available at:
http://www.fda.gov/cber/ltr/allpan090800.pdf
Transcript of discussion of allogeneic pancreatic islets by FDA Biologic Response Modifier Advisory Committee (3/20-21/2000) available at: http://www.fda.gov/ohrms/dockets/ac/cber00.htm
Proposed And Final Rules Impacting Human Islets Federal Register Establishment Registration and Listing for Manufacturers of Human Cellular and Tissue-Based Products; Final Rule (1/2001) available at:
http://www.fda.gov/cber/rules/frtisreg011901.pdf
Federal Register Current Good Tissue Practice for Manufacturers of Human Cellular and Tissue-Based Products; Inspection and Enforcement; Proposed Rule (1/2001) available at:
http://www.fda.gov/cber/rules.htm#gtp
Cell/Tissue Based Documents "Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy" (1998)available at:
http://www.fda.gov/cber/gdlns/somgene.pdf"
Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals" (1993) available at:
http://www.fda.gov/cber/gdlns/ptccell.pdf"
Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use" (1997) available at:
http://www.fda.gov/cber/gdlns/ptc_mab.pdf
Application of GMP to Gene Therapy Products Used in Clinical Trials (5/31/2000)
http://www.fda.gov/cber/summaries/malarkey053100.ppt
Copies of Points to Consider documents are available from:
The Division of Congressional and Public Affairs
CBER
HFM-12
1401 Rockville Pike, Suite 200
N
Rockville, MD 20852-1448
Telephone: (301) 594-0830
Budget and Related Issues
Applicants should complete the budget information as directed in the PHS 398 application form.
Allowable costs
In order to fully achieve the goal of this initiative, 6-8 ICRs are proposed for support. The award will provide up to $750,000 as direct costs per for each ICR.
During the course of the project period, it is anticipated that technologies such as islet cell isolation and shipping, transplantation techniques, and immune suppression will improve and the proposed protocols may change. Accordingly, it is expected that the investigators will adjust their scientific projects to accommodate such changes. During the course of the award, the Steering Committee will meet at least semi-annually and workshops to review new developments in the field will be held periodically.
Applications should present five budget periods of 12 months each that provide adequate budget justification for all applicable direct and F&A costs. An estimate of personnel costs needs, including the principal investigators, other professional and support staff must be included. A minimum effort of 0.25 FTE is required for each ICR director and sub-project principal investigators. Estimates of travel costs to Steering Committee and Data Committee meetings as well as a statement that indicates a willingness to participate in these meetings and share data and concepts must also be included.
Applicants submitting an application requesting $500,000 or more in direct costs for any year must obtain approval from NCRR program staff listed in INQUIRIES before submitting the application. The applicant must identify, in the cover letter that is sent with the application, the NCRR staff member who agreed to accept assignment of the application.
Non-Allowable Costs:
The grant award for this RFA may not be used to pay for patient care costs. Such costs include, but are not limited to: a) transportation and hospital care for organ donors; b) transportation, testing and monitoring of potential islet cell transplantation recipients; and c) inpatient or outpatient costs related to islet cell transplantation or other clinical studies using such preparations.
Plan for Sharing Research Data
Since the overall mission of the ICR consortium is to advance the field of islet transplantation, it is imperative that the members interact in an open and collegial manner, providing insight and sharing data and their own advances and offering innovative ideas at Steering Committee meetings and in other ICR discussions. Applicants must also agree to maintain in confidence information that is presented at said meetings. The means by which the applicant will implement these procedures should be described.
All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared.
Sharing Research Resources
NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and 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 Information1. Criteria
Only the review criteria described below will be considered in the review process.Factors that will be considered in making awards include:
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 NCRR in accordance with the review criteria stated below.
As part of the initial merit review, all applications 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 each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an 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 move a field forward.
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?
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, or technologies for this area?
Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?
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?
Review Criteria
The goals of NIH-supported research are to advance understanding of biological systems, improve the control of disease, and enhance the health of humankind. The scientific and technical merits of the proposed activities and the organizational plans for participating in this cooperative agreement and the extent to which they address the overall goals and objectives of the RFA will be reviewed.
Reviewers will be asked to provide written comments on the ICR applications for:
Responsiveness and innovative approaches to the major objectives of this RFA;
Quality of the pre-clinical data and experience in translating such experience into clinical protocols;
Experience in providing clinical grade islets for both human transplantation and basic laboratory research;
Plans to integrate institutional projects with shared cores and to make cores and resources available to other ICRs and NIH-supported investigators;
Prior experience in organizing and oversight of multi-centered basic and translational research studies and plans to share this within the ICR consortium;
Adequacy of an isolation core, laboratory and ancillary facilities and equipment;
Evidence of institutional support;
Experience in the field of human islet cell research and cellular transplantation research;
Adequacy of the process design, methods, and analyses to be used;
Qualifications of personnel;
Letters of planned or existing collaboration from clinical researchers who will perform pre- and post-transplantation studies using ICR-generated islet cells;
2.A. Additional Review Criteria:
In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:
Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).
Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.
Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.
2.B. Additional Review Considerations
Budget: The reasonableness of the proposed budget 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 the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.
2.D. Sharing Research Resources
NIH policy requires that grant awardee 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 http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://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
1. Award Notices
After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.
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 14 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
The cooperative agreement (U42) will require collaboration among the NCRR Program Coordinator, the NIDDK Program Officer, and the Directors of each ICR in order to assure efficiency and progress toward the stated goals of this RFA. Plans to develop these synergistic relationships should be addressed in each application.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. 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 provided to the ICR Director as well as the 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 ( U42 ), 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 above.
2.A.1. Principal Investigator Rights and Responsibilities
The Principal Investigator will be the Director of the ICR facility and have the primary responsibility to plan and detail the functions of the requisite laboratories and cell isolation facilities and retain primary responsibility for the performance of these activities. The Directors and associates must agree to participate as members of the ICR Steering Committee. The ICR Directors will recommend outside experts to balance the composition and size of the Steering Committee to both provide requisite expertise and guarantee that the entire number of NIH representatives does not exceed 40 percent of the total membership. Each member, including the outside experts, will have one vote on matters discussed at the Steering Committee meeting.
The ABCC Director and the ICR Directors, in cooperation with the other Steering Committee members, will be responsible for developing the details of the ICR operating policies and documents, including the definition of objectives, protocols, implementation, and interaction to establish a clinical islet cell resource program that is responsive, efficient, and ethical.
The ABCC Director will assist the Chairperson of the ICR Steering Committee in organizing Steering Committee meetings. The ABCC will be responsible for administrative matters related to Steering Committee meetings, including preparing agendas, writing and distributing minutes, communicating with outside investigators and the lay public and receiving applications for ICR services from investigators.
In addition, the ABCC will maintain close contact with the ICRs, the NCRR Program Coordinator and NIDDK Program Officer. It will assist in coordinating the research programs and core resources among the ICRs and other relevant NIH-funded programs, provide biostatistical and bioinformatics support to the ICRs, maintain current and relevant databases, arrange appropriate advertising and publicity for the ICRs upon approval by the Steering Committee and prepare a comprehensive annual report for the program in a timely fashion.
The Funding Entities will establish rules governing the selection and tenure of the Chairperson and any outside experts for the Steering Committee. The Chairperson of the Steering Committee, the ABCC Director and each ICR Director must present updates of their activities at each meeting that will be held either by telephone conference call or at a venue determined by the Steering Committee. The ABCC will be responsible for all administrative aspects of the Steering Committee meetings. Individual ICR Directors and the ABCC Director will be responsible for submission of their Annual Progress Reports and other reports to NCRR in compliance with NIH and other Federal Guidelines.
Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
To promote the development of a collaborative program among the award recipients, the Principal Investigator is expected to attend all ICR Steering Committee meetings twice yearly. A major goal of these meetings is to facilitate progress by providing a forum that will lead to sharing skills, ideas, technology, data, and biological reagents. Consequently, all applications submitted through this RFA must include technology transfer and sharing plans for both data and unique research resources that are generated through support of the ICR and in accord with the ICR policies developed by the Steering Committee. It is expected that resources and technologies developed by the ICRs will be made available to the academic research community, after a propriety period agreed upon by the Steering Committee, at no charge other than the cost of production and distribution. Applicants must indicate their willingness to share islet procurement and isolation technologies and include the plan to do so. As a condition of funding, the Principal Investigator must state his/her willingness to collaborate and share data freely with other ICRs.
2.A.2. NIH Responsibilities
One Health Scientist Administrator from the NCRR will be designated to serve as the NCRR Program Coordinator of this cooperative agreement. This individual will assist in coordinating the activities of the awardees and in facilitating exchange of information between them and the Funding Entities.
The NCRR Program Coordinator and one Program Officer from NIDDK will serve on the Steering Committee. NCRR and NIDDK will also designate individuals who will serve as their respective alternates to the Steering Committee. In consultation with the awardees, these individuals and their alternates may convene workshops or sponsor seminars within existing meetings to update the Directors on relevant scientific advances.
As members of the Steering Committee the NCRR Program Coordinator and NIDDK Program Officer participate in all meetings and assist in developing operating policies and procedures but do not to direct the activities of the ICRs. They also serve as liaisons between the Steering Committee and the NIH and as information resources on research activities in cell transplantation and diabetes mellitus and may further facilitate activities by organizing meetings of groups having specific expertise in areas that could augment the research activities described in this RFA.
NIH reserves the right to terminate or modify each ICR award in the event of (a) failure to develop, implement or maintain mutually acceptable basic and clinical research protocols, (b) substantial shortfall in efficiency, data reporting, quality control, or other such major breach in islet cell production, laboratory studies or clinical protocols, (c) substantive changes in an agreed-upon protocol with which the Funding Entities cannot concur, (d) ethical issues, (e) lack of compliance with FDA GMP guidelines, (f) significant non-compliance with other relevant Federal guidelines, (g) failure to fully and openly share data or concepts relevant to advancing the mission of the ICR consortium or (h) activities that are inconsistent with the cooperative nature of this award and serve to disrupt collaborative efforts within the consortium.
2.A.3. Collaborative Responsibilities
The Steering Committee coordinates and facilitates the activities supported by this cooperative agreement.
The members of the Steering Committee will continue to maintain the policies and operating procedures of both itself and the ICRs as described within the ICR Policy and Procedure Document and modify these procedures as necessary. The aforementioned Document will also detail requirements for basic and clinical research protocols to use ICR-generated islets including quality control, quality assurance, testing procedures, human subjects protection, conflict of interest, and intellectual property and regulatory issues as they evolve throughout the duration of the studies. The Steering Committee will also make provisions for an arbitration panel as described below.
The Steering Committee will meet semi-annually.
ICR Directors are also responsible for formulating consistent policies for dealing with recurring situations that require coordinated action at Steering Committee meetings.
Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
2.A.4. Arbitration Process
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual 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 HHS regulations 45 CFR Part 16.
Awardees will be required to submit semi-annual reports to NCRR via the ABCC. The content is described in the current ICR Policy and Procedure document (http://icr.coh.org/). This includes descriptions of pancreata acquired, islets generated, laboratory data produced, mission-relevant subprojects, and outcomes of clinical studies that employed the islets. The reports shall be in both printed and electronic format.
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.
Section VII. Agency ContactsWe 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:
Anthony Hayward, M.D., Ph.D.
Director Division for Clinical Research Resources
National Center for Research Resources
Democracy Plaza One, Room 908
6701 Democracy Blvd. Bethesda, MD 20892
Telephone: (301) 435-0790
FAX: (301) 480-3661
Email: [email protected]
2. Peer Review Contacts:
Sheryl Brining, Ph.D.
Director, Office of Review
National Center for Research Resources
Democracy Plaza One, Room 1074
6701 Democracy Blvd.
Bethesda, MD 20892
Telephone: (301) 435-0809
FAX: (301) 480-3660
Email: [email protected]
3. Financial or Grants Management Contacts:
Ms. Mary Niemiec
Grants Management Officer
Office of Grants Management
National Center for Research Resources
Democracy Plaza One, Room 1046
6701 Democracy Blvd. Bethesda, MD 20892
Telephone: (301) 435-0842
FAX: (301) 480-3777
Email: [email protected]
Required Federal Citations
Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.
Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); 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). All clinical protocols supported by ICR resources must engage a Data and Safety Monitoring Board (DSMB), which will provide overall monitoring of interim data and safety issues. However, these DSMBs should be assembled by the institutions or funding organizations that sponsor those clinical protocols. The ICRs will not develop an independent DSMB but should present a data safety monitoring plan in their applications.
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 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.
Information developed as a result of ICR activities will be held in a central database by the ABCC. Such data, which will include, for example, all laboratory procedures, methods of data analysis and reports, will be made available to the ICR Directors, NCRR Program Coordinator, and NIDDK Program Officer. The database will not be distributed to the public until the relevant studies have been completed and only then with the concurrence of the Steering Committee. The database must be designed to protect patient identity and ensure the privacy of their medical and genetic data.
Awardees are encouraged to publish and to publicly release and disseminate results, data and other information developed by this cooperative agreement. Such documents, written by an individual ICR or by a consortium of ICRs, may be published only after approval by the Steering Committee. However, during or within three years beyond the end date of the project support period, unpublished data, unpublished results, data sets not previously released, or other study materials or products are to be made available to any third party only with the approval of the Funding Entities and in accordance with the stipulations within this document.
Intellectual Property:
The Bayh-Dole Act is implemented through Department of Commerce regulations 37 CFR 401. These regulations define terms, parties, responsibilities, prescribe the order of disposition of rights, prescribe a chronology of reporting requirements, and delineate the basis for and extent of government actions to retain rights. The patent rights clauses are found at 37 CFR Part 401.14 and are accessible from the Interagency Edison web page, http://www.iedison.gov/. ICR awardees will have primary rights to their data developed under these awards, subject to Government rights of access consistent with current Federal policies.
Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm).
All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.
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.
Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.
All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).
Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://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.
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.
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. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.
Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.
Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance as Nos. 93.389 and 93.847 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.
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NIH Funding Opportunities and Notices
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