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 Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) (http://www2.niddk.nih.gov)
Title: Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL) (U01)
Announcement Type
This is a modified reissue of RFA-DK-02-010.
Request For Applications (RFA) Number: RFA-DK-09-003
Catalog of Federal Domestic Assistance Number(s)
93.847
Key Dates
Release Date: December 12, 2008
Letters of Intent Receipt Date: February 19,
2009
Application Receipt
Date: March 19, 2009
Peer Review Date: June/July
2009
Council Review Date: October
2009
Earliest
Anticipated Start Date: December 1, 2009
Additional Information To Be
Available Date (Url Activation Date): Not applicable
Expiration Date: March
20, 2009
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, Review and
Anticipated Start Dates
1.
Letter of Intent
B. Sending an Application to
the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review
Considerations
C. Resource Sharing Plan(s)
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
Nature of the Research Opportunity:
The National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health of the U.S. Department of Health and Human Services is seeking applications to continue the Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL).
The A2ALL network http://www.nih-a2all.org/ currently supported under RFA-DK-02-010 (http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-010.html) began in 2002 with the overall goal of determining the outcomes of donors and recipients who choose LDLT. Additionally funded studies included early molecular markers of liver regeneration, recovery of living donor liver function, treatment of recipients with viral hepatitis C immediately prior to transplant to prevent post-transplant recurrence, and genes related to hepatocellular carcinoma (HCC) progression in LDLT and deceased donor liver transplantation (DDLT).
For this open competition, the FOA requests two separate types of applications: Transplantation Center (TC) applications and Data Coordinating Center (DCC) applications. Funding will be considered for as many as nine TC will and a single DCC. This is a one-time solicitation to continue A2ALL for maximum of five years, contingent on satisfactory study recruitment and retention.
Background Information:
Over the last 30 years liver transplantation has become the standard of care and the only cure for end stage liver disease. Its success has led to over 6,000 transplants performed yearly. But about 16,000 patients remain on the transplantation list awaiting deceased liver donation. LDLT constitutes a relatively small (fewer than 5% in 2007) but important portion of all adult liver transplants. After first gaining popularity in the late 1990s, enthusiasm was later curtailed by two well publicized donor deaths, greater deceased donor donation, and more efficient deceased donor organ allocation. Yet, the high mortality and morbidity of patients waiting for transplant continues to put great pressure on consideration of alternatives to DDLT. LDLT remains the main alternative for expanding the number of transplants. It has continued to evolve, with refinement of donor and recipient selection and improvement in outcomes. Thus while the number of centers performing LDLT has declined from earlier in this decade, many centers remain committed to the procedure through active programs.
The objective of the original 2001 Funding Opportunity Announcement (FOA) that resulted in the formation of A2ALL was to establish and maintain the infrastructure required to accrue and follow sufficient numbers of patients being considered for and undergoing LDLT to provide generalizable data from adequately powered studies. To achieve this objective, a core protocol was instituted at each TC that enrolled potential living donors and their recipients at the time of donor evaluation. Nine TCs and a DCC (University of Michigan) were funded. The network established the following primary and secondary research aims:
A fuller description of the study and its aims is found at http://www.nih-a2all.org/default.asp
The objective of the original FOA was accomplished and has resulted in a number of peer reviewed publications that serve as standards for the knowledge of LDLT in the United States. Accordingly, A2ALL has helped define the benefits and risks of LDLT for both donors and recipients. Among these advances are determination of the survival benefit of the recipient who chooses LDLT, recipient and donor morbidity, and resource utilization before and after LDLT. Informed decision making competence of potential donors has been objectively measured. Disease specific papers on hepatitis C and hepatocellular carcinoma outcomes following LDLT have been published as well as the use of LDLT in fulminant liver failure.
Scientific Knowledge to be Gained:
Despite A2ALL achieving a significant number of its original goals, several important research issues and clinical questions regarding LDLT are still in the process of being addressed or have yet to be addressed. Foremost among these issues is determining the long-term health and well being of living donors. Understanding the safety and efficacy of the procedure has to go beyond short-term issues of post-operative complications of donors and recipients, resource utilization, recovery time, and restoration of adequate liver function. Critical to assessing the long-term health of donors is comparison to the health of persons with similar characteristics who did not donate.
Objectives of this Research Program
The specific objectives of the A2ALL continuation could include but are not limited to:
1) Continuation of the A2ALL prospective longitudinal studies of donor and recipient outcomes through collection and analysis of data and biospecimens.
2) Long-term follow-up of living donor health and health related quality of life.
3) Completion of the clinical trial on pre-transplant HCV treatment and consideration of other treatments to prevent recurrence in the setting of LDLT.
4) Completion of data and sample collection for the study of Genomics and Regeneration in the Transplant Setting (GRITS).
5) Completion of the study of genes related to HCC progression in LDLT and DDLT (GR2HCC).
6) Completion of the study of donor quantitative liver function study.
7) Development and testing of protocols of immune tolerance or minimization of immunosuppression in the LDLT setting.
8) Determination of recipient and donor characteristics that most favor choosing LDLT.
9) Identification and evaluation of newer approaches to LDLT to improve donor and recipient outcomes.
Organization of A2ALL
A2ALL will consist of the following components: the NIH, up to nine TCs, and a DCC. Committees will include a Steering Committee and its subcommittees, an independent Data and Safety Monitoring Board (DSMB), and other committees as needed. The responsibilities of each component of the Network are described in the Terms and Conditions of Award.
NIDDK will be responsible for organizing and providing support for the A2ALL and will be involved substantially with the awardees as a "partner", consistent with the Cooperative Agreement mechanism. A designated NIDDK Project Scientist, who will provide programmatic oversight, will monitor subject recruitment and study progress, ensure disclosure of conflicts of interest and adherence to NIDDK policies. The NIDDK will appoint the Chairperson(s) of the Steering Committee and all members of the DSMB.
Ongoing Clinical studies. A2ALL has current steering committee approved sub-studies (described below) that will be completed during the continuation. Not all transplant centers participate in each of the sub-studies. It is anticipated that the studies will continue with no disruption.
Genes related to Hepatocellular Carcinoma progression in Living Donor and Deceased Donor Liver Transplant (GR2HCC) is a study of the molecular mechanisms related to the progression of hepatocellular carcinoma before transplant and its occurrence after LDLT or DDLT. http://www.vcuhealth.org/transplant/laboratory_research/GR2HCC/gr2hcc.htm
Genomics and Regeneration in the Transplant Setting (GRITS) is a study of early molecular signals in regeneration immediately following hepatectomy and in the first few days of post-LT recovery.
Donor Quantitative Liver Function Testing (DQLFT) study evaluates the extent that living donors recover normal liver function in the months after partial hepatectomy. http://www.nih-a2all.org/default.asp
In addition to these three ongoing studies, a randomized controlled clinical trial entitled Low Accelerating Dose Regimen (LADR) for treatment of patients with viral hepatitis C immediately prior to transplant with the intention of prevention of recurrence of infection after transplant is scheduled to end recruitment in early 2008.
TCs will recruit subjects into the ongoing studies described above until recruitment is terminated. Longitudinal follow-up will continue as described in the study protocols. All individual TCs will be required to participate in a cooperative and interactive manner with one another and with the DCC in all aspects of the A2ALL (see Terms and Conditions of Award). Only investigators who wish to carry out the protocols of the A2ALL and agree to be governed by the policies of the A2ALL and its steering committee should apply under this FOA. It should be noted however, that not all TCs will necessarily participate in all of the approved A2ALL protocols.
The DCC will take on all of the administrative and data collection/analysis functions and will be responsible for all of the ongoing studies. In addition, the DCC will be responsible for supporting any protocol development or modifications; providing sample size calculations, statistical advice, questionnaires, and data analysis; supporting development, implementation, and maintenance of a data base of clinical information and blood samples; developing or modifying any data safety and monitoring plans; supporting manuscript preparation; and providing overall study coordination and quality assurance, including coordination of the activities and meetings (including conference calls) of the Data and Safety Monitoring Board (DSMB), the Steering Committee, and other needed committees. The DCC will prepare or modify protocols for submission to the DSMB and the Steering Committee for their approval prior to the implementation of any study protocols or protocol change. The DCC will be responsible for preparation of documents for submission to the Food and Drug Administration (FDA) in support of Investigational New Drug Applications (INDs) held by the NIDDK on behalf of A2ALL. The DCC will also prepare all reports including data reports for review by the DSMB at their meetings. The DCC will also be responsible for the logistics and planning of the meetings of the Steering Committee and the various operational committees of A2ALL. The Data Coordinating Center will be responsible for acquiring and administering subcontracts as needed. (See Terms and Conditions of Award.) NIDDK has established Central Biosample, Genetic, and Data Repositories for the ongoing and archival storage of data and biospecimens collected in large, multi-site studies funded by NIDDK. http://www.niddkrepository.org
The DCC will work with the NIDDK Biosample Repository and the TCs to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository and dispensed to steering committee approved ancillary study sites. In addition, the DCC will coordinate with the NIDDK repository to prepare the collected data for eventual archiving and distribution. All samples and data transferred to the Repositories will be under the custodianship of NIDDK, although the A2ALL Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time.
Study Governance
STEERING COMMITTEE. A Steering Committee will be the main governing body of the A2ALL (see Terms and Conditions of Award). An Executive Committee comprised of the Study Chair and Co-Chair, if appropriate; the Principal Investigator of the DCC; and the NIDDK Project Scientist also will be convened for management decisions required between Steering Committee meetings, as needed for efficient progress of the study. Other subcommittees of the Steering Committee will be established and will operate as necessary, such as publications, ancillary, protocol, forms, and pathology committees.
DATA SAFETY AND MONITORING BOARD. An independent Data and Safety Monitoring Board (DSMB) will be established by NIDDK to review protocols and monitor patient safety and performance of each study. As a part of its responsibilities, the DSMB will submit recommendations to NIDDK regarding the continuation of each study. The DSMB will be responsible for final approval of the Data and Safety Monitoring Plan developed by the DCC. All protocols or changes to protocols will be approved by local Institutional Review Boards, the Steering Committee, the A2ALL Data and Safety Monitoring Board, and NIDDK before initiation. Any specific collaboration involving the resources of A2ALL will require approval by the Steering Committee and the NIDDK Project Scientist.
See Section VIII, Other Information - Required Federal Citations, for
policies related to this announcement.
Section
II. Award Information
1. Mechanism of Support
This funding opportunity
will use a cooperative agreement award mechanism. In
the cooperative agreement mechanism, the Project Director/Principal
Investigator (PD/PI) retains the primary responsibility and dominant role for
planning, directing, and executing the proposed project, with NIH staff being
substantially involved as a partner with the Principal Investigator, as
described under the Section VI. 2. Administrative
Requirements, "Cooperative Agreement Terms and Conditions of
Award".
2. Funds Available
The
estimated amount of funds available for support of up to nine transplant centers and one data coordinating
center projects awarded as a result of
this announcement is $3.5 million for fiscal year 2009. Future year amounts will depend on annual appropriations.
Because the nature, scope and availability and participation of
qualified study participants will vary across transplant centers, it is
anticipated that the size of each award for the clinical centers will vary but
may not exceed $250,000 in direct costs. Direct costs for the data
coordinating center may not exceed $800,000. 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.
Facilities and
administrative costs requested by consortium participants are not included in
the direct cost limitation, see NOT-OD-05-004.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Section III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
The following
organizations/institutions are eligible to apply:
*Foreign institutions must be located within North America
1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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.
2. Cost Sharing or Matching
This
program does not require cost sharing as defined in the current NIH
Grants Policy Statement.
3. Other-Special Eligibility Criteria
Resubmissions. Applicants are not permitted to submit a resubmission application in response to this FOA.
Renewals. Renewal applications will be permitted for this FOA.
Only TCs that are currently conducting adult to adult LDLT may apply. To be eligible, a TC must have performed a minimum total of 6 adult to adult LDLT during the two year period of 2007-2008.
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 most current PHS 398 research grant application instructions
and forms. Applications must have a D&B Data Universal Numbering System
(DUNS) number as the universal identifier when applying for Federal grants or
cooperative agreements. The D&B number can be obtained by calling (866)
705-5711 or through the web site at http://www.dnb.com/us/.
The D&B number should be entered on line 11 of the face page of the PHS 398
form.
The title and number of
this funding opportunity must be typed in item (box) 2 only of the face page of
the application form and the YES box must be checked.
Foreign
Organizations (Non-domestic
(non-U.S.) Entity)
NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.
Applications from foreign organizations must:
In addition, for applications from foreign organizations:
Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.
3. Submission Dates and Times
Applications must be
received on or before the receipt date described below (Section
IV.3.A). Submission times N/A.
3.A. Receipt, Review and Anticipated Start Dates
Letter
of Intent Receipt Date: February
19, 2009
Application Receipt Date: March 19, 2009
Peer Review Date: June/July 2009
Council Review Date: October 2009
Earliest
Anticipated Start Date: December 1, 2009
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
in Section IV.3.A.
The letter of intent
should be sent to:
Francisco O. Calvo,
Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney
Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 752, MSC 5452
Bethesda, MD 20892-5452
Telephone: (301) 480-8897
FAX: (301) 480-3505
Email: [email protected]
3.B. Sending an
Application to the NIH
Applications must be
prepared using the forms 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:
Francisco
O. Calvo, Ph.D.
Chief, Review Branch
National Institute
of Diabetes and Digestive and Kidney Diseases
National
Institutes of Health
6707 Democracy
Blvd., Room 752, MSC 5452
Bethesda,
MD 20892-5452
Telephone:
(301) 480-8897
FAX: (301)
480-3505
Email: [email protected]
3.C. Application
Processing
Applications must be received on or before the
application receipt date) described above (Section IV.3.A.).
If an application is received after that date, the application may be delayed
in the review process or not reviewed. Upon receipt, applications will be
evaluated for completeness by the CSR and for responsiveness by the reviewing
Institute Incomplete and/or 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 NIH Grants
Policy Statement.
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 renewal award if such
costs: 1) are necessary to conduct the project, and 2) 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 renewal 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 and Information
Supplemental Instructions for Transplant Centers (TC) Applications
Applicants for the TCs that have participated in A2ALL should demonstrate their accomplishments related to their participation in previous collaborative projects within A2ALL (e.g., recruitment of subjects, committee membership or chairmanship, protocol development, ability to follow the protocols, publications, etc.). Applicants for the TCs that have not participated in A2ALL should demonstrate their experience and expertise in conducting collaborative clinical research studies in LDLT. They should also submit a plan for meeting the research objectives of A2ALL.
1. Each TC application must document the underlying liver disease for all potential recipients who had at least one potential donor evaluated for LDLT between January 1, 2007 and December 31, 2008. The underlying liver disease must also be documented for all recipients who received either LDLT or DDLT between January 1, 2007 and December 31, 2008 and had previously had a potential donor evaluated for LDLT.
2. Each TC application must describe its standard procedures for follow-up of donors following LDLT, including frequency and components of evaluation. The TC application must provide detailed plans for future subject recruitment and retention related to the ongoing research studies of A2ALL.
3. Each TC submitting an application must discuss its willingness and ability to carry out the protocols already approved by the A2ALL Steering Committee and protocols that would be approved by the Steering Committee during the extension period. Willingness to participate in the three ongoing sub-studies (see 1. Objectives) should be noted.
4. Each TC application must provide evidence of intellectual engagement by outlining protocols that address clinically significant issues related to LDLT. Two proposals are requested. Within the 25 page research plan, approximately 4 pages total should be reserved for these proposals.
a. Each TC application must propose a study of long-term donor outcomes that could involve both donors who have donated prior to the beginning of the study extension and donors who will donate during the extension. This study must capture all of the potentially significant long-term outcomes for the potential donor, including both health, economic, and social consequences of donation. At least one appropriate comparison group that has not undergone LDLT should be described.
b. A research protocol should be proposed for either an analysis using the existing 10 year A2ALL database or that will require new data and sample collection in the extension. Either proposal must address an important issue related to LDLT and liver disease. It must be hypothesis driven and must include a description of the rationale, research aims, outcome measures, and study design.
Any new protocol must be completed during the 5 year period of this award and be realistic about the time it takes for protocol development and the various levels of approval, including the A2ALL Steering Committee, the DSMB, and individual IRBs. If molecular or other translational studies are proposed, they must be able to inform a clinically significant issue for donors or recipients.
5. Each TC application must show how the TC will be able to submit data to the DCC and biospecimens to the NIDDK Repository (supported by an independent contract from NIDDK) and to central laboratories and biological cores as approved by the Steering Committee. TCs must show how they will work in collaboration with the DCC to implement procedures for uniform data collection, handling and transmittal of data, as well as data audits and other data quality control procedures, as established by the study protocol. TCs must also provide information regarding past contributions to and future plans for involvement with operational committees of A2ALL (e.g. Recruitment, Publications, etc.) and the establishment of uniform procedures and policies.
6. Each TC applicant must describe their plans for retaining study subjects, so that a longitudinal assessment of donor and recipient outcomes can be accomplished.
7. There should be evidence of strong institutional support for the TC, including adequate space in which to conduct clinical and research activities and office space for staff. Institutional resources for patient care and follow-up including personnel, space, and special laboratory facilities must be described in the TC application.
8. An organizational structure for the TC should be set forth in the application, delineating specific personnel (including transplant surgeons and hepatologists as well as any ancillary professional personnel such as pathologists, radiologists, etc.) available to carry out the approved protocols. The principal investigator should state his or her general support of collaborative research and interaction with NIDDK, the other TCs, and the DCC through the Network concept. Applicants should discuss their willingness, and that of the institutions involved, of pursuing a per patient basis (capitation) of operational costs.
9. TCs must be able to interact with the DCC to transmit and edit data and should discuss their capability to participate in a distributed data entry system.
10. TCs applications should delineate the responsibilities of the investigators and staff for carrying out the A2ALL protocols, including (but not limited to) donor and recipient recruitment and retention, histological and radiographic assessments, data collection and entry, and sample collection and shipment. The TC applicant should consider the responsibilities for interacting with the DCC in monitoring visits, data audits, and responses regarding missing data, data discrepancies, missed patients visits, missing samples, and any other irregularity that could affect the results and integrity of the study.
Supplemental Instructions for Data Coordinating Center (DCC)
The application for the DCC must demonstrate experience in the coordination of multi-center liver transplantation studies in all phases from start up (e.g., protocol development, manual of operation) through analysis and publication. The DCC applicant should describe any previous interactions with A2ALL and its role in the development of policies, procedures, protocol development and publications. The applicant should propose an expert in liver transplantation as a member of the staff or key collaborator.
It is expected that the PI of the DCC will be a leader in the network. Therefore, a description of past and potential future participation in such a role must be included.
The DCC applicant must also address the following regarding responsibilities and requirements for the DCC.
1. Participation in the design of all research studies and the development or updating of the manual of operation, data collection forms, and questionnaires;
2. Development and implementation of systems for communication among Steering Committee members and among study sites;
3. Training of all TC personnel who are responsible for data entry; monitoring of adherence to the research plan, completeness of data collection and the quality of data, including on-site monitoring;
4. Data collection, editing, processing, analysis and reporting to assure timely reporting to the NIDDK, the investigators and the DSMB; development of frequently updated reports that track the completeness and quality of all critical data elements by center, including protocol driven events such as liver biopsies and tissue collection.
5. Establishment of procedures that insure the safety and confidentiality of all records.
6. Procedures for coordinating submission of biospecimens from the TCs to the NIDDK Repository, central laboratories, and to ancillary study participants.
7. Ability to fill out necessary regulatory documents in support of the Food and Drug Administration Investigational New Drug Applications (IND) and other regulatory documents, including annual reports, and submission of adverse event reports.
8. Committee management, including those currently functioning (Steering, Ancillary Studies, Publication, Coordinators, and Specific Disease (Hepatitis C and HCC) Committees) as well as those that might be required for either a limited or extended period during the extension (such as Protocol, Forms, and Recruitment and Retention Committees).
9. In addition to addressing the above listed standard DCC functions, each DCC application must propose a study of long-term donor outcomes that could involve both donors who have donated prior to the beginning of the study extension and donors who will donate during the extension. This study must capture all of the potentially significant long-term outcomes for the potential donor, including both health, economic, and social consequences of donation. At least one appropriate comparison group that has not undergone LDLT will be required. The proposal must consider a study design and participant burden that will result in as complete participation as possible. Within the 25 page research plan, approximately 2 pages total should be reserved for this proposal.
Other Special Performance Requirements
A2ALL will continue to be a collaborative effort that will require frequent interactions of awardees among themselves and with NIDDK. Applicants must explicitly indicate their willingness to:
1. Participate in Steering Committee meetings (expected to occur in person 3-4 times a year and as monthly teleconferences, or as needed), site visits required by NIDDK, and regular telephone conference calls;
2. Cooperate with other awardees in the development and design or modification of research protocols, and cooperate with other awardees in carrying out approved research protocols;
3. Abide by common definitions; common methods for patient selection and enrollment; and common protocols, procedures, tests, and reporting forms as chosen by majority vote of the Steering Committee;
4. Actively seek to implement each consortium-wide protocol approved by the DSMB and NIDDK that the site is selected for participation;
5. Comply with all study policies and quality assurance measures approved by the Steering Committee;
6. Agree to oversight of the study by a Data and Safety Monitoring Board (DSMB),
7. Accept awards for the support of research based on per-patient (capitated) rates and the actual numbers of subjects enrolled, followed, and completing the study (TCs only);
8. Transmit study data to the DCC in a timely and accurate manner;
9. Report all adverse events in accordance with procedures established by the Steering Committee and NIDDK policies;
10. Cooperate with other awardees in the publication of study results and the eventual release to the scientific community of study procedures and other resources;
11. Serve on and chair subcommittees as assigned by the steering committee or NIDDK;
12. Accept the “Cooperative Agreement Terms and Conditions of Award” in Section VI.2.A “Award Administration Information”.
Additional submission requirements for the preparation of the Detailed Budget
Transplant Center
The budget must include support for a clinical study coordinator with effort proportional to the anticipated volume of patient enrollment and a maximum of 2.4 month effort for the applicant principal investigator and other investigators.
Requested budgets must also include funds for travel to the Bethesda, Maryland area for three Steering Committee meetings annually for two investigators and a study coordinator.
Data Coordinating Center
The DCC application budget should include costs managing the DSMB as well as the cost of supporting a meeting three times per year in Bethesda Maryland. Approximately $50,000 for the entire 5 years should be budgeted for the meetings of the DSMB.
Research Plan Page Limitations
The research plan page limit is 25 pages. For the TC applications, approximately 4 pages should be reserved for the 2 research proposals. For the DCC application, approximately 2 pages should be reserved for the long-term donor outcome proposal.
Appendix Materials
All paper PHS 398 applications must provide appendix material on CDs only. Include five identical CDs in the same package with the application (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.).
Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.
Resource Sharing Plan(s)NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.
(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.
(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.
(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.
The DCC application should include an overall sharing plan for data generated during the funding of A2ALL. TC applications need not cite this plan in detail, but applicants should indicate their willingness to participate fully in it. The plan should indicate specifically what will be shared, with whom it will be shared (including the NIDDK Data Repository), when it will be shared, the means by which it will be shared, and conditions that will apply to recipients of shared data. This plan must be approved by the NIDDK before awards will be issued under this FOA.
Specific Instructions for Foreign Applications
All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.
Section V. Application Review Information
1. Criteria
Only the review
criteria described below will be considered in the review process.
2. Review and Selection Process
Applications that are complete and responsive to the FOA will
be evaluated for scientific and technical merit by an appropriate
peer review group convened by NIDDK and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/),
using the review criteria stated below.
As part of the scientific peer review, all applications will:
The following will be considered in making funding decisions:
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 meritorious 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? Is it likely that the goals of the research plan will be
achieved? What is the scientific and technical merit of the approach to
meeting the requirements of the integration of the currently approved studies
or the research plan of the biological cores?
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)? Additionally,
do the specific competence and previous experience of the professional,
technical and administrative staff of the TC or the DCC increase the likelihood
that the goals of the research plans will be achieved?
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? Do the collaborative arrangements within the proposed Network enhance the productivity of the TC or DCC?
In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the priority score.
Review of the TC applications will also be based on the following specific criteria:
Recruitment and Retention: Is there evidence that the TC evaluates and transplants enough LDLT candidates to meaningfully contribute? Have they demonstrated their willingness and ability to recruit and retain these patients in clinical studies?
Requested research proposals: Is the proposal for donor follow-up feasible and likely to lead to important information on long term donor outcomes? If the application proposed an analysis of existing A2ALL data, will it result in information that will further the understanding and management of patients being considered for or undergoing LDLT? If the application proposed a study that would require new data and sample collection, is the study feasible and likely to lead to significant new clinical information on LDLT?
Data and Sample Management: Is there an adequate plan to ensure the timely and accurate transmission of study data to the DCC and patient samples to the NIDDK repository and approved central laboratories or biological cores?
Cooperative Experience: Is there evidence of a strong willingness to work cooperatively and to participate in all aspects of a cooperative network including service on subcommittees and authoring publications and proposals?
Review of the DCC application also will be based on the following specific criteria:
Is the applicant experienced in the coordination of all phases of a multi-center liver transplantation study?
Does the applicant understand the scientific, statistical, logistical, and technical issues underlying the A2ALL network and have the knowledge necessary to lead in the areas of study design, statistics, logistics, data acquisition and management, identification of and coordination with central laboratories and serum/tissue/data repositories, handling of laboratory specimens, quality control, data analysis, and consortium coordination?
Are the proposed plans adequate for acquisition, transfer, management, and analysis of data, quality control of data collection and monitoring, and overall coordination of the A2ALL activities?
Is there sufficient expertise, training, and experience of the investigators and staff, including the administrative abilities of the Principal Investigator and co-investigators, and is the time they plan to devote to the effective coordination of A2ALL adequate?
Are the administrative, supervisory, and collaborative arrangements sufficient for achieving the goals of the network, including willingness to work cooperatively with the principal investigators of the TCs and NIDDK?
Are the proposed facilities, equipment, and organizational structure sufficient to effectively coordinate the A2ALL activities in implementing the protocols, data collection and providing for specialized methodologies and plans for collecting and distribution of biospecimens to the NIDDK repositories, and ancillary study investigators?
Does the applicant demonstrate the ability to develop or modify the Data Safety and Monitoring Plan, Manuals of Operations and Case Report Forms?
Is there ability to support the NIDDK in filing the necessary applications and reports associated with INDs to the Food and Drug Administration?
Is there sufficient expertise in setting up and managing databases?
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 rating:
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 on Human
Subjects in the PHS 398 instructions).
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 on Human Subjects in the
PHS 398 instructions).
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to
be used in the project, the five points described in the Vertebrate Animals
section of the Research Plan 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.
Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.
2.C. Resource Sharing Plan(s)
When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.
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 PD/PI 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.
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 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.
2.
A.1. Principal Investigator Rights and Responsibilities
The Principal
Investigator will have the primary responsibility for: all aspects of the protocols, including any modification of
study design; conduct of the study including participant recruitment, safety
and follow-up; assuring quality of patient care and protocol adherence; data
collection; quality control; data and safety monitoring, data analysis and
interpretation; preparation of publications; and collaboration with other
investigators, unless otherwise provided for in these terms or by action of the
Steering Committee. Awardee(s) agree to the governance of the study through a
Steering Committee. Awardees will be required to accept and implement the
common protocol(s) and procedures approved by the Steering Committee, the NIDDK
and the Data and Safety Monitoring Board.
All applicants will be required to participate in a cooperative and interactive manner with one another and with the DCC in all aspects of A2ALL.
Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The collaborative protocol and governance policies will call for the continued submission of data centrally to the DCC for a collaborative database; procedures for data analysis, reporting and publication; and procedures to protect and ensure the privacy of medical and genetic data and records of individuals. The NIDDK Project Scientist, on behalf of the NIDDK, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.
All awardees will be responsible for implementing the clinical trials and studies according to the protocols and methodologies decided upon by the Steering Committee. For a study involving multiple institutions, it is the responsibility of each awardee/site to ensure that data will be submitted in a timely manner to the central Data Coordinating Center. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.
Awardees are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) for clinical trials, as simple as appropriate in order to encourage maximum participation of physicians and patients and to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. For research involving multiple awards, strategies for the analyses of pooled data will be developed by the Steering Committee. No site may publish or share data collected at their own individual site while following a A2ALL protocol in accordance with policies, including the data sharing plan, approved by Steering Committee.
Awardees are responsible for submitting interim progress reports, when requested, to the NIDDK Project Scientist including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the Steering Committee may require additional information from individual awardees/sites. Such reports are in addition to the annual awardee noncompeting continuation progress report
Awardees are responsible for establishing procedures, where applicable, for all participating institutions in coordinated awards to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects, and the NIH policy requirements for the inclusion of women, minorities and children.
The DCC will be involved in collaborations with the NIDDK and the TCs during all phases of the study. Thus, the DCC is expected to work cooperatively with TCs and sponsoring organizations in multicenter studies and oversee the implementation of and adherence to a common protocol, as well as assure quality control of the data collected and storage of collected specimens. In addition to organizing and attending regular meetings, the Data Coordinating Center will be expected to maintain close communications with the NIDDK Project Scientist and the Principal Investigators of the TCs.
Awardees are encouraged to publish and to publicly release and disseminate results, data and other products of the study, concordant with the study protocol and governance and the approved plan for making data and materials available to the scientific community and the NIDDK. In addition they will adhere to the steering committee’s approved publication/presentation policy. No individual site will be permitted to publish site-specific results that compete and interfere with the integrity of study-wide reports of the results of the A2ALL Study Group.
Support or other involvement of industry or any other third party in any study performed by the Network -- e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIDDK support; or special access to project results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification to, and concurrence by the NIDDK.
Upon completion of the
project, the DCC is expected to transfer all study intervention materials and
procedure manuals into the NIDDK Central Repository, which in accordance with
current NIDDK and NIH policies, will make them available to the scientific
community for the conduct of research at no charge other than the costs of reproduction
and distribution.
Awardees will retain custody of and have primary
rights to the data and software developed under these awards, subject to
Government rights of access consistent with current HHS, PHS, and NIH policies.
2. A.2. NIH Responsibilities
An NIH Project Scientist will have substantial
programmatic involvement that is above and beyond the normal stewardship role
in awards, as described below.
The NIDDK Project Scientist responsibilities include:
1. Retaining overall programmatic responsibility for the award, and will clearly specify to the awardee the name(s) and role (s) of any additional individuals with substantial involvement in the project and the lines of reporting authority.
2. Interacting with the principal investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the principal investigator and staff, periodic site visits for discussions with awardee research teams, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains the option of periodic external review of progress.
3. Reviewing and approving protocols to insure they are within the scope of peer review and for safety considerations, as required by Federal regulations. The NIDDK Project Scientist will monitor protocol progress, and may request that enrollment in a protocol study be terminated for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; and (f) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure (except for patients already on-study).
4. Making recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
NIDDK reserves the right to terminate or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol, (b) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which NIDDK cannot concur, (d) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (e) human subject ethical issues that may dictate a premature termination.
NIDDK will name additional scientific advisors as necessary from within the National Institutes of Health whose function will be to assist the NIDDK Project Scientist and the Steering Committee in carrying out the goals and aims of the approved studies. NIDDK will have one vote for all key study group subcommittees, regardless of the number of NIDDK personnel involved.
The Project Scientist will have substantial scientific programmatic involvement in quality control, interim data analysis, safety monitoring, and final data analysis and interpretation, preparation of publications, and coordination and performance monitoring. The dominant role and prime responsibility for these activities resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NIDDK Project Scientist.
Other NIDDK Project Scientist responsibilities and levels of involvement in the project:
1. Participates in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or designee will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.
2. Serves as a resource with respect to other ongoing NIDDK activities that may be relevant to the protocol to facilitate compatibility and avoid unnecessary duplication of effort.
3. Has substantial involvement in assisting in the design and coordination of research activities for awardees:
Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
2.A.3. Collaborative Responsibilities
The Steering Committee, composed of each of the Principal Investigators of the TC and the DCC, and the NIDDK Project Scientist will be the governing board of the study. Only the principal investigators, and the NIDDK Project Scientist or designee will be voting members of the Steering Committee and all major scientific decisions will be determined by a majority vote. This committee will have the primary responsibility for approval of the common protocols, facilitating the conduct of participant follow-up, monitoring completeness of data collection and timely transmission of data to the DCC, and reporting the study results. It will also be responsible for establishing Network policies in such areas as access to patient data, ancillary studies, publications and presentations, and performance standards.
A Chairperson or Chairpersons will be chosen from among the Steering Committee members by the NIDDK from among the principal investigators (but not the NIDDK Project Scientist or Data Coordinating Center Principal Investigator) or alternatively, from among experts in an appropriate scientific field who is not participating directly in the study. In collaboration with the PI of the DCC and the NIDDK Project Scientist, the Chairperson is responsible for coordinating the Committee activities, for preparing meeting agendas, and for scheduling and chairing meetings.
Subcommittees will be established on topics such as ancillary studies, publications and presentations, quality control, recruitment, protocol adherence, among others. PIs and other investigators may serve as chairs of the subcommittees.
An Executive Committee comprised of the Study Chair(s), the Principal Investigator of the Coordinating Center, and the NIDDK Project Scientist will be convened to effect management decisions required between Steering Committee meetings, as needed for efficient progress of the trial.
Each TC Awardee and the DCC Awardee agree to the governance of the study through the Steering Committee. Meetings of the Steering Committee will ordinarily be held by telephone conference calls or at rotating sites of the TCs and the DCCs.
The NIDDK Project Scientist (and the other cited NIDDK scientists) may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g., issues of recruitment, intervention, follow-up, quality control, standards and methods, adherence to protocol, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment. Regardless of the number of NIH staff participating in technical advisory roles, the NIDDK will be limited to one vote on the Steering Committee.
An independent Data and
Safety Monitoring Board (DSMB) will be established by the NIDDK to review
protocols and monitor patient safety and performance of each study. As a
part of its responsibilities, the DSMB will submit recommendations to the NIDDK
regarding the continuation of each study. The DSMB will be responsible for
final approval of the Data and Safety Monitoring Plan developed by the DCC.
Because the DSMB serves as an independent group advisory to the NIDDK, study
investigators will not communicate with the Board members regarding study
issues, except as authorized by the Board’s Executive Secretary or the
NIDDK Project Scientist.
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.
3. Reporting
Awardees will be
required to submit the Non-Competing
Continuation Grant Progress Report (PHS 2590) annually and financial
statements as required in the NIH Grants
Policy Statement.
A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.
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:
James Everhart, MD, MPH
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive
and Kidney Diseases
6707 Democracy Boulevard, Room 655
Bethesda MD 20892-5450
Telephone: (301) 594-8878
FAX:
(301) 480-8300
E-mail: [email protected]
2. Peer Review Contacts:
Francisco O. Calvo, Ph.D.
Division
of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707
Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
Telephone:
(301) 594-8885
FAX:
(301) 480-3505
Email: [email protected]
3. Financial or Grants Management Contacts:
Ms.
Sharon Bourque
Division
of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707
Democracy Boulevard, Room 719
Bethesda, MD 20892-5456
Telephone:
(301) 594-8846
FAX:
(301) 594-9523
Email: [email protected]
Section VIII. Other Information
Required Federal Citations
Use of Animals in
Research:
Recipients of
PHS support for activities involving live, vertebrate animals must comply with
PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf)
as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm),
and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm)
as applicable.
Human
Subjects Protection:
Federal
regulations (45CFR46) require that applications and proposals involving human
subjects must be evaluated with reference to the risks to the subjects, the
adequacy of protection against these risks, the potential benefits of the
research to the subjects and others, and the importance of the knowledge gained
or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Data and
Safety Monitoring Plan:
Data and safety
monitoring is required for all types of clinical trials, including physiologic
toxicity and dose-finding studies (phase I); efficacy studies (Phase II);
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 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.
Policy
for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see http://grants.nih.gov/grants/gwas/
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.
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.
NIH Public Access Policy Requirement:
In
accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html)
investigators must submit or have submitted for them their final, peer-reviewed
manuscripts that arise from NIH funds and are accepted for publication as of
April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly
available no later than 12 months after publication. As of May 27, 2008,
investigators must include the PubMed Central reference number when citing an
article in NIH applications, proposals, and progress reports that fall under
the policy, and was authored or co-authored by the investigator or arose from
the investigator’s NIH award. For more information, see the Public
Access webpage at http://publicaccess.nih.gov/.
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 FOA 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. 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 two years to the research. For further
information, please see: http://www.lrp.nih.gov.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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