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Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)

Components of Participating Organizations
National 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.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

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.


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