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: Data Coordinating Center for the HALT-Polycystic
Kidney Disease Trials (U01)
Announcement Type
This is a
reissue of RFA-DK-01-029,
which was previously released May 29, 2001.
Request For Applications (RFA) Number: RFA-DK- 07-008
Catalog of Federal Domestic Assistance Number(s)
93.849
Key Dates
Release Date: October
10, 2007
Letters of Intent
Receipt Date: November
20, 2007
Application
Receipt Date: December
13, 2007
Peer Review Date(s): March-April 2008
Council Review Date: May 2008
Earliest Anticipated
Start Date: August 1, 2008
Additional
Information To Be Available Date (09/13/07): http://www2.niddk.nih.gov/NR/rdonlyres/175578F6-62B4-429A-9BBF-96CCEC2FFB3A/0/KUHHALTPKDPROTOCOL9107.pdf
Expiration
Date: December
14, 2007
Due Dates for E.O. 12372
Not Applicable
Additional Overview
Content
Executive Summary
Table of Contents
Part
I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and Submission Information
1. Address to Request Application
Information
2. Content and Form of Application
Submission
3. Submission Dates and Times
A. Receipt and Review and
Anticipated Start Dates
1. Letter of
Intent
B. Sending an Application to
the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review
Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award
Dates
Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy
Requirements
A. Cooperative Agreement Terms
and Conditions of Award
1. Principal
Investigator Rights and Responsibilities
2. NIH
Responsibilities
3. Collaborative
Responsibilities
4. Arbitration
Process
3. Reporting
Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)
Section VIII. Other Information - Required Federal
Citations
Part II
- Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
NIDDK has a longstanding interest in supporting both basic and clinical studies of autosomal dominant polycystic kidney disease (ADPKD), and issued an RFA in 2001 to support clinical trials of ADPKD. From that RFA, in 2002 five cooperative agreements were awarded to four participating clinical centers (PCC) and one data coordinating center (DCC), to form a HALT-PKD Consortium, which designed the HALT-PKD clinical trials (http://clinicaltrials.gov/ct/show/NCT00283686?order=200). The HALT-PKD Consortium is governed by a Steering Committee comprised of PCC and DCC Principal Investigators (PI), a Steering Committee Chair and an NIDDK Project Scientist.
The HALT-PKD trials are investigating the efficacy of renin-angiotensin-aldosterone system (RAAS) blockade in altering progression of kidney disease in patients with ADPKD. Although a wealth of evidence from several well-designed and rigorous studies shows RAAS blockade with angiotensin converting enzyme inhibitors (ACE-I ) to be of benefit in slowing renal progression in diabetic kidney disease, a definitive study demonstrating efficacy of RAAS blockade, with (ACE-I) and/or angiotensin receptor blockers (ARB), on renal progression in ADPKD has not been performed. ACE-I block conversion of angiotensin I (ANG I) to angiotensin II (ANG II) and these drugs are commonly used for the treatment of hypertension in the general population and in ADPKD patients. Systemic ANG II levels do not suppress completely with chronic ACE-I therapy alone, however, and both systemic and renal hemodynamic responses to exogenous ANG I and ANG II infusions persist in the presence of ACE-I. Studies have shown further suppression of ANG II and aldosterone when ARB therapy is added to maximal ACE-I therapy. This may be particularly relevant in ADPKD, as studies of PKD tissue extracts demonstrate exuberant interstitial inflammation with mast cells with chymase-like activity. Reports indicate significantly greater ANG II production despite ACE-I blockade in PKD tissues as compared with non-PKD controls. As ANG II levels and action are important in regulating blood pressure and renal plasma flow and in promoting cyst growth in ADPKD, the HALT-PKD trials were designed to test whether combination therapy with ACE-I and ARB can maximally block ANG II production and action, and alter progression of disease.
The HALT-PKD trials consist of two multicenter randomized clinical trials that are testing intensive RAAS blockade using ACE-I/ARB combination versus ACE-I monotherapy and targeting different levels of kidney function: (Study A) early disease defined by GFR >60 mL/min/1.73 m2, and (Study B) moderately advanced disease defined by GFR 30-60 mL/min/1.73 m2. Both Studies have a two-year enrollment phase, which began in early 2006. It is anticipated that the patient follow-up phase of the Studies will end by late 2012, and will be followed by a 6-month study close-out period. Participants enrolled in Study A will be followed for a total of four years, while those enrolled in Study B will be followed for four-to-six years, with the average length of follow-up being five years. There are currently seven patient enrolling sites for HALT-PKD, including Emory University, the Mayo Clinic, Kansas University, the Cleveland Clinic Foundation, University of Colorado, Tufts University and Beth Israel Medical Center.
In Study A, the effect of study medication on structural progression at two different levels of blood pressure control is assessed using a 2x2 factorial design. Accordingly, 548 hypertensive ADPKD participants are randomized to one of four study arms: 1) combination ACE-I/ARB with standard blood pressure (BP) control (systolic 120-130 and diastolic 70-80 mm Hg); 2) ACE-I monotherapy with standard BP control; 3) combination ACEI/ ARB treated to a low BP target (systolic 95-110 and diastolic 60-75 mm Hg); and 4) ACE-I treated to the low BP goal. Other antihypertensive agents are added as needed to meet the BP goals. The primary outcome of Study A is the percent change in total kidney volume measured by magnetic resonance imaging (MRI). Secondary outcome measures include: i) rate of change of GFR; ii) rate of change in renal blood flow; iii) change in left ventricular mass by MRI; iv) rate of change in albuminuria; v) rate of change in 24-hour urine aldosterone excretion; vi) all-cause hospitalizations; vii) hospitalizations due to cardiovascular cause; viii) the frequency of PKD related symptoms or medical conditions (e.g., ruptured renal cyst) ix) quality of life and pain measured using the SF-36v2 and HALT-PKD Pain Questionnaire; and x) adverse effects of medications.
Study B compares ACE-I/ARB combination therapy to ACE-I monotherapy on the time to a 50% reduction of baseline estimated GFR, ESRD or death. All 472 hypertensive ADPKD participants are treated to a standard level of blood pressure control (systolic 110-130 mm Hg and diastolic 80 mm Hg), with addition of other antihypertensive agents as needed. Secondary outcome measures include: i) rate of change in albuminuria; ii) rate of change in 24-hour excretion of aldosterone; iii) all-cause hospitalizations; iv) hospitalizations due to cardiovascular cause; v) the frequency of PKD related symptoms or medical conditions (e.g., ruptured renal cyst); vi) quality of life and pain measured using the SF-36v2 and HALT-PKD Pain Questionnaire; and vii) adverse effects of medications.
For both Studies, the titration of medications and addition of open-label antihypertensive agents in the trials is based on home blood pressure readings. At the first screening visit, participants are consented for Screening and Drug Washout and trained to monitor blood pressure at home. Screening laboratory measurements are also drawn at this visit. After review of the screening laboratory measurements, selected participants initiate a 2-4 week drug washout if required. Participants begin the treatment regimen once two central serum creatinine results have been checked and verified. The study drug is titrated over three subsequent visits, two weeks apart (conducted over the telephone). Serum potassium, creatinine and BUN are checked between dose increments at the PCC or a local lab. Once study drugs have been maximized and blood pressure stabilized, home blood pressure records are reviewed every three months (by phone or in clinic). Study visits at the PCC occur at the 4th and 12th months in the first year and every 6 months thereafter. The study drug and open label antihypertensive medications are adjusted to maintain BP goals over the duration of the study. Serum creatinine is measured centrally every 6 months in participants of both studies after the first year. Study A participants undergo kidney MRI, MR renal blood flow analysis, and cardiac MRI performed at the PCC at baseline, 24 and 48 months. All imaging studies results are then transferred electronically to a central imaging facility for analysis. Further information regarding the HALT-PKD protocols can be found at: http://www2.niddk.nih.gov/NR/rdonlyres/175578F6-62B4-429A-9BBF-96CCEC2FFB3A/0/KUHHALTPKDPROTOCOL9107.pdf
The original DCC and clinical centers were initially funded for seven years. Due to considerable administrative delays in initiating HALT-PKD, the DCC and the PCCs must be recompeted to finish the study. The PCCs will be recompeted by a separate RFA. The primary objective of this RFA is to provide for continued DCC support so that HALT-PKD data collection and analysis can be completed as planned. The HALT-PKD DCC will provide coordination, assistance, centralized data management and analytical support for all HALT-PKD Studies. The DCC responsibilities include logistical support for the HALT-PKD Steering Committee. Specifically, the DCC will provide assistance in the following areas:
If the DCC funded from the RFA is a new institution to the HALT-PKD consortium, NIDDK will arrange for timely transfer of data sets and study operations to the new DCC.
This RFA is not intended to support the HALT-PKD clinical centers.
See Section
VIII, Other Information - Required Federal Citations, for policies related to this
announcement.
Section
II. Award Information
1. Mechanism(s) of Support
This funding opportunity
will use the U01
Cooperative Agreement award mechanism(s).
As an applicant, you
will be solely responsible for planning, directing, and executing the proposed
project.
This funding opportunity
uses just-in-time concepts. It also uses the modular as well as the non-modular
budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are
submitting an application with direct costs in each year of $250,000 or less,
use the modular budget format described in the PHS 398 application
instructions. Otherwise follow the instructions for non-modular research grant
applications.
The NIH U01 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". Plans for this cooperative agreement project beyond the current funding
opportunity are indefinite.
2. Funds Available
NIDDK intends to commit approximately $1.0 million dollars in FY 2008 to fund one HALT-PKD DCC as a new grant in response to this RFA. An applicant may request
a project period of up to five years and a budget for direct costs up to $700,000 dollars per year.
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.
Section
III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
You may submit (an)
application(s) if your organization has any of the following characteristics:
Foreign institutions are not eligible to apply as the
primary institution, but may enter into a consortium or subcontract with a
domestic institution as the primary applicant.
1.B. Eligible Individuals
Any
individual with the skills, knowledge, and resources necessary to carry out the
proposed research is invited to work with their institution to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.
Individuals applying as Principal Investigators for the DCC
should have expertise in the management of large interventional drug trials,
including a Masters Degree or Doctorate in Clinical Epidemiology,
Biostatistics, or a related field, as well as experience in the studies of
kidney disease.
2. Cost Sharing or Matching
Not
Applicable
The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing
3. Other-Special Eligibility Criteria
Applicant
institutions may submit more than one application, however, individuals may
appear as key personnel on only one application. Organizations submitting
applications need not be affiliated with an existing HALT-PKD clinical center.
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: GrantsInfo@nih.gov.
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 on line 2 of the face page of the application form and the YES box
must be checked.
Foreign Organizations
Several special provisions apply to applications
submitted by foreign organizations:
Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, 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
Letters of Intent
Receipt Date: November 20, 2007
Application
Receipt Date: December 13, 2007
Peer Review
Date(s): March April 2008
Council Review
Date: May 2008
Earliest
Anticipated Start Date: August 1, 2008
3.A.1. Letter of Intent
Prospective applicants
are asked to submit a letter of intent that includes the following information:
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows 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.
The letter of intent
should be sent to:
Dr.
Francisco Calvo
Chief, Review Branch
National Institute of Diabetes, Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: calvof@niddk.nih.gov
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:
Dr.
Francisco Calvo
Chief, Review Branch
National Institute of Diabetes, Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: calvof@niddk.nih.gov
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 NIDDK. Incomplete and non-responsive applications will not be
reviewed.
The NIH will not accept
any application in response to this funding opportunity that is essentially the
same as one currently pending initial review, unless the applicant withdraws
the pending application. However, when a previously unfunded application,
originally submitted as an investigator-initiated application, is to be
submitted in response to a funding opportunity, it is to be prepared as a NEW
application. That is, the application for the funding opportunity must not
include an Introduction describing the changes and improvements made, and the
text must not be marked to indicate the changes from the previous unfunded
version of the application.
Information on the status of an application should be
checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.
4. Intergovernmental Review
This initiative is not
subject to intergovernmental review.
5. Funding Restrictions
All NIH awards are
subject to the terms and conditions, cost principles, and other considerations
described in the NIH Grants Policy Statement. The Grants Policy Statement can
be found at http://grants.nih.gov/grants/policy/policy.htm.
Pre-award costs are
allowable. A grantee may, at its own risk and without NIH prior approval, incur
obligations and expenditures to cover costs up to 90 days before the beginning
date of the initial budget period of a new or competing continuation award if
such costs: are necessary to conduct the project, and would be allowable under
the grant, if awarded, without NIH prior approval. If specific expenditures
would otherwise require prior approval, the grantee must obtain NIH approval
before incurring the cost. NIH prior approval is required for any costs to be
incurred more than 90 days before the beginning date of the initial budget
period of a new or competing continuation award.
The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project.
See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.
6. Other Submission Requirements
Plan for Sharing Research
Data
The precise content of
the data-sharing plan will vary, depending on the data being collected and how
the investigator is planning to share the data. Applicants who are planning to
share data may wish to describe briefly the expected schedule for data sharing,
the format of the final dataset, the documentation to be provided, whether or
not any analytic tools also will be provided, whether or not a data-sharing agreement
will be required and, if so, a brief description of such an agreement
(including the criteria for deciding who can receive the data and whether or
not any conditions will be placed on their use), and the mode of data sharing
(e.g., under their own auspices by mailing a disk or posting data on their
institutional or personal website, through a data archive or enclave).
Investigators choosing to share under their own auspices may wish to enter into
a data-sharing agreement. References to data sharing may also be appropriate in
other sections of the application.
All applicants must
include a plan for sharing research data in their application. The data sharing
policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding
to this funding opportunity should include a description of how final research
data will be shared, or explain why data sharing is not possible.
The 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.
Data sharing in the HALT-PKD
consortium will have three components: (1) Data sets from clinical centers will
be shared within the HALT-PKD consortium during the clinical trials, becoming
part of a common data set that will be maintained at the DCC and that will be
the basis for analysis of study endpoints. (2) The HALT-PKD consortium will
also publish their research results and share with the scientific community and
the general public. (3) The HALT-PKD data set will ultimately be transferred to
the NIDDK Data Repository after the clinical trials have been completed and the
primary data paper (s) published. Applicants should indicate their willingness
to comply with HALT-PKD consortium plans for both components of data sharing.
Sharing Research Resources
NIH policy expects that grant
recipients make unique research resources readily available for research
purposes to qualified individuals within the scientific community after
publication (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 Information
1. Criteria
Only the review criteria
described below will be considered in the review process.
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 NIDDK 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? Are the plans for data collection, management and quality control
adequate? The applicant must provide plans to ensure the complete, reliable and
timely management of study data from the clinical centers, as well as specific
plans to address problems with missing data, incorrectly entered data and data
cleaning. The applicant should also provide plans for scheduling steering
committee meetings, and for generating and distributing regular reports to the
Steering Committee and to the NIDDK-appointed DSMB. Are the plans for
statistical and analytic support sufficient? Are the plans for oversight of
medication and patient sample tracking for the study adequate?
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? Individuals applying as Principal Investigators for the DCC should have
expertise in successfully managing large interventional drug trials, including
a Masters Degree or Doctorate in Clinical Epidemiology, Biostatistics, or a
related field, as well as experience in studies of kidney disease. Other
proposed key personnel should also have experience in operations of large
interventional clinical trials, including those conducted under Investigational
New Drug applications from the US Food and Drug Administration.
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? Is there
evidence of previous experience and accomplishments in the design and analysis
of large-scale interventional trials and datasets, and of the availability of
an infrastructure adequate to support the appropriate storage, management, and
analysis of data generated by human subjects research, including genetic
sequencing data?
2.A. Additional Review
Criteria:
In addition to the above
criteria, the following items will continue to be considered in the
determination of scientific merit and the priority score:
Protection
of Human Subjects from Research Risk: The involvement of human subjects and protections from
research risk relating to their participation in the proposed research will be
assessed (see the Research Plan, Section E on Human Subjects in the PHS Form
398).
Inclusion
of Women, Minorities and Children in Research: The adequacy of plans to
include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated (see the Research Plan, Section E on Human Subjects in
the PHS Form 398).
Biohazards: If materials or procedures
are proposed that are potentially hazardous to research personnel and/or the
environment, determine if the proposed protection is adequate.
2.B. Additional Review
Considerations
Budget: The reasonableness of the
proposed budget 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 expects that
grant recipients make unique research resources readily available for research
purposes to qualified individuals within the scientific community after
publication (See the NIH Grants Policy Statement 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.
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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).
A formal notification in the form of a Notice
of Award (NoA) will be provided to the applicant organization. The NoA
signed by the grants management officer is the authorizing document. Once all
administrative and programmatic issues have been resolved, the NoA will be
generated via email notification from the awarding component to the grantee
business official (designated in item 12 on the Application Face Page). If a
grantee is not email enabled, a hard copy of the NoA will be mailed to the
business official.
Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Also Section
IV.5. Funding Restrictions.
2. Administrative and National
Policy Requirements
All NIH grant and
cooperative agreement awards include the NIH Grants Policy Statement as part of
the NoA. For these terms of award, see the NIH Grants Policy Statement Part II:
Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and
Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific
Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
The following
Terms and Conditions will be incorporated into the award statement and will be
provided to the Principal Investigator as well as to the appropriate
institutional official, at the time of award.
2.A. Cooperative Agreement
Terms and Conditions of Award
The following special
terms of award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS grant administration regulations at 45 CFR Parts
74 and 92 (Part 92 is applicable when State and local Governments are eligible
to apply), and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for
this program will be the cooperative agreement (U01),
an "assistance" mechanism (rather than an "acquisition"
mechanism), in which substantial NIH programmatic involvement with the awardees
is anticipated during the performance of the activities. Under the cooperative
agreement, the NIH purpose is to support and stimulate the recipients'
activities by involvement in and otherwise working jointly with the award
recipients in a partnership role; it is not to assume direction, prime
responsibility, or a dominant role in the activities. Consistent with this
concept, the dominant role and prime responsibility resides with the awardees
for the project as a whole, although specific tasks and activities may be
shared among the awardees and the NIH as defined below.
2.A.1. Principal
Investigator Rights and Responsibilities
The
Principal Investigator will have the primary responsibility for: working with other HALT-PKD investigators in all
aspects of the study protocols and procedures, including any modification of
study design, conduct of the study, data collection, quality control and study
adherence, data analysis and interpretation, preparation of publications, and
relevant reports for the steering committee, the NIDDK-appointed external
advisory committee (s), appropriate regulatory or safety authorities, and the
NIDDK. The PI is expected to work cooperatively with Clinical Centers and sponsoring organizations in a multicenter study and oversee the
implementation of and adherence to common protocols, as well as assure quality
control of the data collected and its subsequent analysis. The DCC will
schedule, organize and perform clinical site visits as required, during the
conduct of the clinical trials. In addition to scheduling, organizing
(including developing the agenda with the HALT-PKD investigators) and attending
regular meetings and monthly telephone conferences, the DCC will be expected to
maintain close communications with the NIDDK Project Scientist and the PIs of
the Clinical Centers. The DCC will perform analyses as outlined in the HALT-PKD
protocols, and as suggested by the members of the HALT-PKD Steering Committee,
as well as propose original analyses to the collaborative group for their
consideration. The DCC will prepare periodic reports on recruitment, quality
control, study adherence, patient safety, and final results to the Steering
committee, the NIDDK and the NIDDK-appointed external advisory committee (s).
Additional interim analyses, as requested by NIDDK or the EAC will also be
prepared.
The DCC will establish, maintain and provide appropriate oversight to subcontracts for Central Laboratories, study medication distribution and other necessary adjuncts to the study, as necessitated in the study protocols. For all Central Laboratories collected for HALT-PKD, the DCC will coordinate coding, shipping, and receipt in collaboration with study sites, and regularly monitor data quality control from the Central Laboratories.
The NIDDK has established Central Biosample, Genetic, and Data Repositories for the archival and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The DCC will work with the NIDDK Biosamples Repository and the PCCs to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository. 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 the NIDDK, although the HALT-PKD Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time.
The PI responsibilities regarding HALT-PKD Steering
Committee membership are described under Collaborative Responsibilities.
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 NIDDK 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 will serve as a voting member of the Steering Committee and
will participate in all Committee activities, serving as a resource with
respect to the study design and implementation.
The NIDDK Project Scientist, together with the Steering Committee, will review the performance of each participating Center through consideration of the annual reports, sites visits, compliance with the Consortium procedures, meeting timeliness, adherence to uniform data collection procedures, and the timeliness and quality of data reporting. The NIDDK Project Scientist may contribute, through review, comment, analysis, and/or authorship, to reporting results of consortium studies to the investigator community and other interested scientific and lay organizations.
The NIDDK reserves the right to terminate or curtail any study or any individual award in the event of (a) substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or Consortium policy and procedure, (b) substantive changes in a study protocol that are not in keeping with the objectives of the RFA, and/or a human subject ethical issues that may dictate a premature termination.
Additionally,
an NIDDK Program Scientist 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 is the governing board of the HALT-PKD Consortium; its
actions and decisions will be determined by majority vote. Voting members of
the Steering Committee include a Steering Committee Chair, the four primary PCC
and the DCC PIs and the NIDDK Project Scientist. The Committee has the primary
responsibility for determining the study protocol, monitoring the conduct of
the study and reviewing data prior to reporting of study results. It is also
responsible for determining study policies in such areas as access to participant
data, ancillary studies, publication and presentations, and quality standards.
It is anticipated that there will be two Steering Committee meetings held each
year in the Washington DC Metro area.
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 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.
We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research, peer review, and financial or grants
management issues:
1. Scientific/Research Contacts:
Dr. Catherine M. Meyers
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 641
Bethesda, Maryland 20892-5458
Telephone: (301) 594-7717
FAX (301) 480-3510
Email: meyersc@extra.niddk.nih.gov
Dr. Laura Moen
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 623
Bethesda, Maryland 20892-5458
Telephone: (301) 594-7717
FAX (301) 480-3510
Email: moenl@niddk.nih.gov
2. Peer Review Contacts:
Dr.
Francisco Calvo
Chief, Review Branch
National Institute of Diabetes, Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: calvof@niddk.nih.gov
3. Financial or Grants Management Contacts:
Ms. Carey
Beckley
Grants Management Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive and Kidney
Diseases
National Institutes of Health
6707 Democracy Boulevard, Room 725
Bethesda, Maryland 20892-5456
Telephone: (301) 594-8833
FAX: (301) 594-9523
E-mail: beckleyc@mail.nih.gov
Section VIII. Other Information
Required Federal Citations
Human Subjects
Protection:
Federal regulations
(45CFR46) require that applications and proposals involving human subjects must
be evaluated with reference to the risks to the subjects, the adequacy of
protection against these risks, the potential benefits of the research to the subjects
and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Data and Safety
Monitoring Plan:
Data and safety
monitoring is required for all types of clinical trials, including physiologic
toxicity and dose-finding studies (phase I); efficacy studies (Phase II);
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.
Access to Research
Data through the Freedom of Information Act:
The Office of Management
and Budget (OMB) Circular A-110 has been revised to provide access to research
data through the Freedom of Information Act (FOIA) under some circumstances.
Data that are (1) first produced in a project that is supported in whole or in
part with Federal funds and (2) cited publicly and officially by a Federal
agency in support of an action that has the force and effect of law (i.e., a
regulation) may be accessed through FOIA. It is important for applicants to
understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place
data collected under this funding opportunity in a public archive, which can
provide protections for the data and manage the distribution for an indefinite
period of time. If so, the application should include a description of the
archiving plan in the study design and include information about this in the
budget justification section of the application. In addition, applicants should
think about how to structure informed consent statements and other human
subjects procedures given the potential for wider use of data collected under
this award.
Inclusion of Women
And Minorities in Clinical Research:
It is the policy of the
NIH that women and members of minority groups and their sub-populations must be
included in all NIH-supported clinical research projects unless a clear and
compelling justification is provided indicating that inclusion is inappropriate
with respect to the health of the subjects or the purpose of the research. This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43). All investigators proposing clinical research should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the
updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy
incorporates: the use of an NIH definition of clinical research; updated racial
and ethnic categories in compliance with the new OMB standards; clarification
of language governing NIH-defined Phase III clinical trials consistent with the
new PHS Form 398; and updated roles and responsibilities of NIH staff and the
extramural community. The policy continues to require for all NIH-defined Phase
III clinical trials that: a) all applications or proposals and/or protocols
must provide a description of plans to conduct analyses, as appropriate, to
address differences by sex/gender and/or racial/ethnic groups, including
subgroups if applicable; and b) investigators must report annual accrual and
progress in conducting analyses, as appropriate, by sex/gender and/or
racial/ethnic group differences.
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:
NIH-funded investigators
are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an
electronic version of the author's final manuscript upon acceptance for
publication, resulting from research supported in whole or in part with direct
costs from NIH. The author's final manuscript is defined as the final version
accepted for journal publication, and includes all modifications from the
publishing peer review process.
NIH is requesting
that authors submit manuscripts resulting from 1) currently funded NIH research
projects or 2) previously supported NIH research projects if they are accepted
for publication on or after May 2, 2005. The NIH Public Access Policy applies
to all research grant and career development award mechanisms, cooperative
agreements, contracts, Institutional and Individual Ruth L. Kirschstein
National Research Service Awards, as well as NIH intramural research studies.
The Policy applies to peer-reviewed, original research publications that have
been supported in whole or in part with direct costs from NIH, but it does not apply
to book chapters, editorials, reviews, or conference proceedings. Publications
resulting from non-NIH-supported research projects should not be submitted.
For more
information about the Policy or the submission process please visit the NIH
Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or
other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_Manual.htm).
Standards for
Privacy of Individually Identifiable Health Information:
The Department of Health
and Human Services (DHHS) issued final modification to the "Standards for Privacy
of Individually Identifiable Health Information", the "Privacy
Rule", on August 14, 2002 . The Privacy Rule is a federal regulation under
the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that
governs the protection of individually identifiable health information, and is
administered and enforced by the DHHS Office for Civil Rights (OCR).
Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/) provides information on the
Privacy Rule, including a complete Regulation Text and a set of decision tools
on "Am I a covered entity?" Information on the impact of the HIPAA
Privacy Rule on NIH processes involving the review, funding, and progress
monitoring of grants, cooperative agreements, and research contracts can be
found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs in NIH
Grant Applications or Appendices:
All applications and proposals
for NIH funding must be self-contained within specified page limitations. For
publications listed in the appendix and/or Progress report, internet addresses
(URLs) must be used for publicly accessible on-line journal
articles. Unless otherwise specified in this solicitation, Internet
addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation
to view the Internet sites. Furthermore, we caution reviewers that their
anonymity may be compromised when they directly access an Internet site.
Healthy People 2010:
The Public Health
Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This PA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.
Authority and
Regulations:
This program is described in the Catalog of Federal Domestic
Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under the authorization of Sections 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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