Sickle Cell Disease Clinical Research Network

RFA Number: RFA-HL-05-006

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 Heart, Lung and Blood Institute (NHLBI), (http://www.nhlbi.nih.gov/)

Announcement Type
New

Catalog of Federal Domestic Assistance Number(s)
93.839

Key Dates

Release Date: December 3, 2004
Letters Of Intent Receipt Date(s): March 25, 2005
Application Receipt Dates(s): April 25, 2005
Peer Review Date(s): September to November 2005
Council Review Date(s) : February 2006
Earliest Anticipated Start Date: April 1, 2006
Additional Information To Be Available Date (Url Activation Date):
Expiration Date: April 26, 2005

Due Dates for E.O. 12372
Not Applicable.

Executive Summary

The purpose of this initiative is to establish a Clinical Research Network (CRN) of up to 15 clinical centers to design and perform multiple therapeutic trials for treatment of patients with sickle cell disease (SCD) and to establish a Data Coordinating Center for the network. In addition, one or two patient outcomes research cores may be funded. The NHLBI intends to commit approximately $4,000,000 (total costs) in FY 2006 and approximately $36,000,000 (total costs) over a 5 year period to support the SCD CRN. The network will use a U10 cooperative agreement mechanism for support. Eligible organizations include those for profit or non-profit, private or public (such as universities, colleges, hospitals and laboratories), units of state and local governments and eligible agencies of the federal government. Finally, community-based and faith-based organizations are eligible to apply. Applying centers are restricted to the United States of America but may include satellites from foreign countries. 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. Women, individuals in underrepresented racial and ethnic groups and individuals with disabilities are always encouraged to apply. Each investigator may submit only one application for a Clinical Center, a Data Coordinating Center or a Patient Outcomes Core. However, the same institution may apply for each of these with different investigators.

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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
    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
      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
    3. Merit Review Criteria
      A. Additional Review Criteria
      B. Additional Review Considerations
      C. Sharing Research Data
      D. Sharing Research Resources

  Section VI. Award Administration Information
    1. Award Notices
    2. Administrative Requirements
     A. Cooperative Agreement Terms and Conditions of Award
        1. Principal Investigator Rights and Responsibilities
        2. NIH Responsibilities
        3. Collaborative Responsibilites
        4. Arbitration Process
    3. Award Criteria
    4. 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

Background

Sickle Cell Disease affects about 70,000 Americans most of whom are of African descent. Because of its low prevalence, this disease is classified as a “rare” or “orphan disease.” As such, there is no incentive for industry to develop therapies that target sickle cell disease or the other hemoglobinopathies. NHLBI has had a Congressional mandate to address the issue of these diseases since 1972, with the Sickle Cell Disease Act and the Cooley's Anemia Act passed in that year. Worldwide, persons with these disorders number in the millions. During the past 30 years, the lifespan of persons with these disorders has increased from the teens into the forties and fifties. The adult years of the person with both disorders is increasingly burdened by cumulative co-morbidities and disability.

A number of clinical studies require translational efforts if known approaches are to be tested and reach the point of clinical care. A registry that includes phenotypes would be most important if genetic vs. epigenetic contributions to the disease are to be quantified. Many potential drugs, including new inducers of HbF, nitric oxide donors, membrane-active compounds that act in multiple ways including modifying ion channels, and rheologic agents will soon be or are ready for Phase III trials. Novel therapeutic interventions developed for ischemic strokes may add value in managing patients with SCD and reducing their morbidity and mortality.

Specific Objectives for the Sickle Cell Disease CRN

The NHLBI Comprehensive Sickle Cell Centers Program includes approximately 5,000 patients who can participate in Phase I and II studies. A mechanism to move these studies to Phase III trials does not exist currently. The purpose of this initiative is to establish a clinical research network that can translate results from basic and Phase I/II studies into Phase III trials in patients with SCD and when appropriate thalassemia. Specific objectives are to: test the efficacy and effectiveness of new therapies to treat and prevent SCD complications; create data sets that can be used to better characterize patients and their clinical course; apply genomic and proteomic techniques for improved diagnostic and therapeutic approaches; and expand the clinical application of multimodal therapies in SCD.

Approach

This initiative will establish a sickle cell disease clinical research network comprising up to 15 clinical centers that will enroll 50 or more patients per center per year for participation in multiple trials using common protocols that will evaluate treatment modalities.

To recruit an adequate number of patients, a center may subcontract with one or more clinical facilities to obtain suitable sickle cell patients for inclusion in the trial. Clinical trials in this network need to be completed in a reasonable period of time. Each clinical center must have access to 500 research subjects or more, personnel experienced in clinical research, and have an appropriate laboratory infrastructure. To access 500 subjects, centers may recruit satellite institutions or hospitals for additional sickle cell patients. Also, it is expected that the Clinical Centers and satellite institutions will partner with community resources and outreach facilities to facilitate the recruitment of patients.

An efficient framework for such trials is the multi-center, multi-study research network model currently in use in several NHLBI clinical treatment networks. For patients who may require studies other than out-patient services, the availability of a clinical research center at the institution or hospital may be needed.

A Data Coordinating Center (DCC) will be created to assist in the overall function of the SCD-CRN. DCC duties will include coordination of the clinical protocols among the participating centers as well as reimbursement for patient costs associated with the trial. The DCC will also be responsible for data management and analysis.

The SCD CRN will include a Protocol Review Committee (PRC), and a Data and Safety Monitoring Board (DSMB) that will be advisory to the NHLBI. A Steering Committee, composed of the Principal Investigator from each Clinical Center and the Data Coordinating Center, and the NHLBI Project Scientist, will select the specific trials to be performed, establish criteria for the inclusion of patients, identify critical data elements including patients' characteristics, develop detailed protocols for the trials, and assure analysis and publication of results from the trials.

Through the collaborative effort of the SCD CRN, approaches with multi-drug treatment, including combination therapy, and other treatment modalities can be rigorously evaluated. Examples of possible treatment trials, but not limited to these, are those which use drugs in combination with hydroxyurea.

The Clinical Centers of the SCD CRN will collectively perform multiple randomized, controlled clinical trials during the 5-year project period. Each protocol will be implemented at more than six Clinical Centers. However, as many centers as possible will be encouraged to participate in each trial. The specific protocols to be implemented by the SCD CRN will be determined according to procedures detailed below, after the network is established. The primary objective of each protocol will be to test whether a defined treatment approach favorably alters clinical outcome in a population of patients with sickle cell disease.

A Hemoglobinopathies Coordinating Committee (HCC) will be established by representatives of NHLBI whose purpose will be to facilitate coordination of existing clinical studies involving sickle cell disease and thalassemia subjects. The DCC will be responsible for the logistical support of this coordinating committee.

Examples of Research Topics

Project Organization

The SCD CRN will consist of the following components: the NHLBI Project Scientist, up to 15 Clinical Centers, a Data Coordinating Center (DCC), a Steering Committee and its subcommittees, a Protocol Review Committee, and a Data and Safety Monitoring Board (DSMB). The responsibilities of each component of the SCD CRN are described below.

NHLBI. The NHLBI will be responsible for organizing and providing support for the SCD CRN and will be involved substantially with the awardees as a “partner”, consistent with the Cooperative Agreement funding mechanism. A designated NHLBI Project Scientist will monitor protocol development subject recruitment and study progress, ensure disclosure of conflicts of interest and adherence to NHLBI policies. The DCC will be responsible for fiscal management of the network, including calculation of capitation budget rates and awards with approval by the NHLBI Project Scientist and an NHLBI Grants Management Specialist. The NHLBI will appoint the Chair of the Steering Committee and members of the Hemoglobinopathies Coordinating Committee, the Protocol Review Committee and the DSMB.

Clinical Centers. The Principal Investigator at each Clinical Center will have primary responsibility for study design and implementation, including subject recruitment and safety. With the assistance of Co-Investigators as appropriate, the Principal Investigator will hire and supervise relevant personnel, obtain Institutional Review Board (IRB) approval for SCD CRN protocols, oversee data collection and adherence to quality assurance measures, and prepare budgets and annual reports. The Principal Investigator (or designated alternate) will serve as a voting member of the Steering Committee. A Clinical Coordinator at each clinical center will set up training systems, certify personnel, and establish procedures to ensure adherence to protocols, collection of high quality data, and accurate transmission of data to the DCC. Centers are strongly encouraged to involve community resources and outreach facilities in their efforts to recruit and maintain patients in the study.

Data Coordinating Center (DCC). The DCC will assist protocol development, provide statistical consultation for study design, and prepare operational timetables. The DCC will develop data collection forms and manuals of operations, determine sampling and randomization schemes, and assist in defining primary and secondary outcomes and analytical approaches for the protocols. The DCC will subcontract to external laboratories, as needed, coordinate with suppliers of drugs, and arrange for the preparation and packaging of medications.

The DCC will develop procedures for quality control, training and certification, and data management. It will monitor the quality and quantity of data received from the Clinical Centers; provide relevant reports to the NHLBI, Clinical Centers, and Steering Committee; and serve as a central repository for study data. The DCC will prepare protocols for submission to the Protocol Review Committee and prepare confidential data analyses and reports for the DSMB. It will support manuscript preparation through data analysis, statistical consultation, editorial support, and meeting coordination. The DCC will schedule and make arrangements for all meetings of SCD CRN committees and boards. The DCC will manage and distribute protocol funds to participating Clinical Centers as a fee for service arrangement after a protocol has been approved and the NHLBI has released the funds for distribution. The DCC will be subject to annual administrative review.

Hemoglobinopathies Coordination Committee (HCC). NHLBI representatives will assemble a Hemoglobinopathies Coordination Committee that will be responsible for facilitating the overall coordination of clinical studies that will be ongoing in the SCD CRN, the Comprehensive Sickle Cell Centers, the Thalassemia CRN and other efforts as necessary. The HCC will be composed of eight to ten senior investigators with expertise in the clinical aspects of sickle cell disease and thalassemia. The HCC is expected to meet every 2 months by teleconference call and twice a year in face-to-face meetings. These meetings will be arranged by the DCC and should be included in their budget.

Steering Committee. Voting members of the Steering Committee will include the Principal Investigator from each Clinical Center (or designated alternate), the Principal Investigator from the Data Coordinating Center (or designated alternate), the NHLBI Project Scientist, and a Chair appointed by the NHLBI. The Chair of the Steering Committee (who may or may not be a Principal Investigator of a participating Clinical Center) will plan network activities, oversee its functions, and conduct the Steering Committee meetings. The Steering Committee will develop and ensure compliance with SCD CRN policies and procedures, identify and prioritize topics for investigation, evaluate protocols proposed by the Clinical Centers, and develop protocols for submission to the Protocol Review Committee. The Steering Committee will ensure that studies are properly conducted and monitored, that data are appropriately analyzed and interpreted, and that study results are reported in the scientific literature in a timely manner and disseminated to physicians involved in the care of sickle cell disease patients. Subcommittees, consisting of qualified individuals from the clinical centers, the DCC, and the NHLBI, may be established by the Steering Committee to perform specific functions such as Publications and Presentations or Quality Control.

Protocol Review Committee. The PRC will be appointed by, and responsible to, the NHLBI. It will consist of a Chair and scientists with expertise in basic and clinical research, clinical trial design, biostatistics, and outcome measures. Clinical scientists knowledgeable about sickle cell disease but who are not participating at a designated Clinical Center could be invited to assess treatment protocols. The Protocol Review Committee will evaluate protocols proposed by the Steering Committee based on the importance of the question to be addressed, scientific merit of the experimental design, feasibility, appropriateness to a CRN, and consistency with NHLBI mission and policies. The Protocol Review Committee will provide a written critique of each protocol and a final recommendation to the NHLBI. All study protocols implemented by the SCD CRN must first be recommended by the Protocol Review Committee and approved by the NHLBI.

Data Safety and Monitoring Board (DSMB). The NHLBI will establish a DSMB in accordance with established policies (see http://www.nhlbi.nih.gov/funding/policies/dsmb_inst.htm) to ensure data quality and participant safety and to provide independent advice to the NHLBI regarding progress and the appropriateness of study continuation.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the U10 award mechanism(s).

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 and National Policy Requirements, "Cooperative Agreement Terms and Conditions of Award" described below. The project period for studies supported through this RFA will be 5 years. The anticipated award date is April 1, 2006.

This RFA uses just-in-time concepts and a non-modular budget. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

2. Funds Available

The NHLBI intends to commit approximately $4 million (total costs) in FY 2006, and approximately $36,000,000 (Total Costs) over a 5-year period to support the SCD CRN. Total Costs include Direct Costs and Facility & Administrative Costs, also called indirect costs or overhead. It is anticipated that up to 15 Clinical Centers and one Data Coordinating Center will be established under this program. Additional funds may be provided to support a Patient Outcomes Core in one or more of the Clinical Centers. The proposed budget for a Clinical Center applicant may not exceed $110,000 direct costs per year. If applying for a Patient Outcomes Core, a clinical center can add $100,000 direct costs. The proposed budget of a Data Coordinating Center applicant may not exceed $1,000,000 direct costs per year. In addition, the DCC should request not more than $4,000,000 per year in years 2 through 5 in the Patient Care category for the distribution of approved protocols. The final amount will be determined by NHLBI. Specific instructions for budget preparation are in the SUPPLEMENTAL INSTRUCTIONS, below. Awards made to a particular center under this RFA will depend in part on the protocols carried out by the SCD CRN and may be more or less than the requested budget. Although the financial plans of the NHLBI provide support for the SCD CRN, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. Designated funding levels are subject to change at any time prior to award, due to unforeseen budgetary, administrative, or scientific developments. Fiscal and administrative costs are not included in the direct cost limitation, see NOT-OD-04-040.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

Institutions may submit (an) application(s) if they have any of the following characteristics:

An institution may apply for both a Clinical Center and the DCC. In this case the institution must submit separate applications and budgets, and there must be no overlap of key personnel to ensure that data acquisition is independent of data analysis.

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 programs.

2. Cost Sharing

There is no required cost sharing , matching, or cost participation without which an application would be ineligible. http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria

The SCD CRN will be a collaborative effort that will require frequent interactions among awardees among themselves and with the NHLBI. Applicants should explicitly indicate their willingness to:

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. For further assistance contact GrantsInfo, Telephone (301) 435-0714, 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 PHS 398 research grant application instructions and forms (rev. 09/2004). Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

See Section VI.2 Administrative Requirements for additional information.

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.

Clinical Centers must include the description of both protocols within the 25 pages of the grant application. Additional details may be included in an appendix if necessary.

The Data Coordinating Centers may use up to 35 pages for the body of their grant applications.

If a Center includes a Patient Outcomes Research Core, it must be restricted to10 pages and placed at the end of the Center Application describing the two protocols. These 10 pages are in addition to the normal 25 pages allotted for the body of the grant application. The Patient Outcomes Research Core budget page should follow the Protocol budget pages. The inclusion of the Patient Outcomes Research Core should be clearly shown in the Table of Contents.

3. Submission Dates
Applications must be received on or before April 25, 2005.

3.A. Receipt, Review and Anticipated Start Dates

Letter of Intent Receipt Date: March 25, 2005
Application Receipt Date(s): April 25, 2005
Peer Review Date: September to November 2005
Council Review Date: February 2006
Earliest Anticipated Start Date: April 1, 2006

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Dr. Valerie Prenger
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
6701 Rockledge Dr., Room 7214, MSC 7924
Bethesda, Maryland 20892-7924
Bethesda, Maryland 20817 (for express/courier service)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: prengerv@nhlbi.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. 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)

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Dr. Valerie Prenger
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
6701 Rockledge Dr., Room 7214, MSC 7924
Bethesda, Maryland 20892-7924
Bethesda, Maryland 20817 (for express/courier service)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: prengerv@nhlbi.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 listed in the heading of this funding opportunity. If an application is received after that date, it will be returned to the applicant without review. Applications will be evaluated for completeness by CSR.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All 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 (See also Section VI.3. Award Criteria)

6. Other Submission Requirements

Clinical Centers

Applications for Clinical Centers should describe the study personnel and their expertise within the field of SCD, their clinical research experience in sickle cell disease and thalassemias, the research environment of the applicant institution, their access to the necessary patient populations, and the availability of resources needed to conduct clinical trials. Details should be given for developing any collaborative arrangements to recruit the requisite number of study patients.

An application must include a Research Plan describing two clinical trial(s) that could be used as a model for the development of CRN-wide study protocols. Clinical Centers selected to participate in the SCD CRN will be asked to present their proposed protocols to the Steering Committee for consideration, but the SCD CRN may choose not to implement the protocols proposed by a participating center. The proposed protocols should address important questions in the clinical management of SCD and have practical implications for patient care. Randomized, controlled trials that require more subjects than would be available at a single center are preferred. The protocols must be feasible within the 5 year project period. While some protocols proposed by centers will not be selected by the steering committee for network study, it is expected that all centers will participate in one or more of the protocols that are selected.

The Research Plan should describe the specific aims of the research, relevant background information, preliminary data if available, the proposed treatment protocols, study design, study population and methods such as randomization schemes, data collection and analysis. The background section and any preliminary data should provide the rationale and feasibility for the studies and justify the proposed end points and sample sizes. The protocol descriptions should include the expected subject population demographics, inclusion and exclusion criteria, methods for characterizing subject, details of the therapeutic and control interventions, outcome measures to be employed, plans for data analysis and interpretation, timelines, and plans for data sharing and dissemination of study results.

To calculate sample sizes, applicants may assume that six times the number of subjects at their center will be enrolled across all centers. Recruitment estimates for the center should be justified on the basis of the number of new SCD patients seen each year at the applicant institution and the documented history of success in recruiting similar subjects for previous clinical trials at that institution, including data on the participation of women and underrepresented minority and ethnic populations in previous studies. Applicants should demonstrate their abilities to interface with community resources and outreach facilities to recruit and maintain patients into each of the studies.

A Clinical Center applicant should request a project period of 5 years. The budget request for the first year may include up to $110,000 direct costs to support core research activities, and up $100,000 direct costs for the support of a Patient Outcomes Core (optional, see below). The core research activities budget should cover a minimum of 25% effort for the combined physician leadership (Principal Investigator and any Co-Investigators), appropriate percentages of effort for other key personnel (e.g., Clinical Coordinator, data entry clerk), travel costs for approximately four trips the first year to develop treatment protocols and, thereafter, three trips each year to attend Steering Committee meetings in Bethesda, MD; and other travel costs related to CRN operations. For centers submitting a Patient Outcomes Core a separate budget page for this core should follow the budget pate for the Center.

A separate budget table to identify the per-patient costs and total costs should be included with each protocol proposal. These budgets should be based on the two specific protocols proposed in the application and reflect anticipated costs for simultaneous implementation in the first year. Applicants should indicate for each protocol how many patients are available in the applicant's center and how many will be required from the network. The center's estimate of eligible patients should be based on the actual number of patients with that particular clinical problem treated in the year 2004. Protocol Direct Costs should include drugs or laboratory tests that are not clinically indicated, or are not eligible for third-party reimbursement as a part of routine clinical care. Applicants should identify the potential source(s) for all drugs involved in the protocols. If donations from a pharmaceutical company are anticipated, applicants should provide documents that indicate the willingness of the source to contribute to the study and should also describe contingency plans and anticipated extra costs should the arrangements not develop as expected. Funding may not be requested for the purchase of equipment over $10,000. Distribution of protocol funds will be based on the approved protocols actually carried out by the SCD CRN and may be more or less than the budget identified in the application. Protocol funds are not to be included in the budget requests for the clinical sites. They are to be identified as proposed costs in a separate table. Therefore, the total costs on the application face page should reflect the core costs. Protocol funds will be distributed by the DCC once the per patient costs have been established for approved protocols.

Patient Outcomes Core

A clinical center may propose studies focused on patient-oriented outcomes, co-occurring disorders such as depression, patient preference for different treatments and quality of life. Innovative approaches designed by multidisciplinary teams should be used to advance the field of outcomes research in sickle cell disease, similar to work that has been done in other diseases such as cardiovascular disease, diabetes, hemophilia and asthma.

Observational studies are appropriate if they will provide the preliminary data for designing and evaluating interventions to affect, or instruments to measure, patient-centered outcomes. Developmental projects may be proposed if their products will be useful for translation into clinical research studies or implementation in outcomes research. Proposed projects may examine quality of life, patient satisfaction, prevention and treatment of co-morbidities that occur across the lifespan of patients with SCD; service delivery models and their implementation in community settings. Examples of projects include:

The Patient Outcomes Core should be directed by an investigator with expertise in outcomes research and training in a related scientific discipline such as epidemiology, psychology, or biostatistics. Clinical Center and DCC applications are eligible to apply for a Patient Outcomes Core.

Proposals for a Patient Outcomes Core should include two or more short-term (i.e., one to three-year) projects that will develop and test tools or methodologies, or test innovative non-medical interventions that can be disseminated to other centers in the CRN, the CSCC, and other sickle cell centers. The tools, methodologies and interventions should be designed so that, after the projects are complete, they can be disseminated and easily implemented within centers' existing clinical programs, and will not require extra personnel.

The research plan for the Patient Outcomes Core must include specific aims, a background section, preliminary data if any, study population, implementation plans and methods section. A timeline and separate budget with staff's percent effort must be included.

Although, the NHLBI plans to fund up to two Patient Outcome Cores, the awards are contingent upon the availability of funds and the receipt of a sufficient number of meritorious proposals for the Core.

A proposal for a Patient Outcomes Core will be evaluated in terms of its potential to develop and validate sickle cell disease specific measures, create a database that can be linked with a patient registry and other databases and provide high quality data that will be used to measure the functioning and well being of patients, or help demonstrate effectiveness of medical interventions. Other review considerations include the standard review criteria (i.e., significance, approach, innovation, investigator, environment, and experience and capabilities).

The Patient Outcomes Core should be described within 10 pages and appended to the end of the Center application. These 10 pages are in addition to the 25 pages allowed for the Center application. This section should be clearly described in the Table of Contents for the PHS 398 form.

Data Coordinating Center (DCC)

DCC applicants should document experience and expertise in the many aspects of coordinating multi-center clinical trials; including development of data forms, protocols, and manuals of operations; staff training; data collection and management; quality assurance; data analysis; distributed data entry; electronic communications; and administrative management and coordination. Experience in coordinating studies of blood disease and the availability to the DCC of expertise in sickle cell disease are desirable.

DCC applications should discuss the familiarity and experience of the Principal Investigator and other Key Personnel with clinical trial design and implementation; including issues of IRB approvals; eligibility criteria; baseline and outcome measures; methods of randomization; sample size and power calculations; data collection, entry, and transmission; monitoring the accuracy of data collection; quality control; labeling and handling of specimens and drugs; approaches for statistical analysis; and procedures required to ensure that all protocols are performed in a manner consistent with United States Food and Drug Administration guidelines. The DCC application should also describe plans for communications and interactions with the NHLBI, Clinical Centers, the Protocol Review Committee, and the DSMB.

Applicants for the DCC should prepare categorical budgets for five 12-month periods, not to exceed $1,000,000 direct costs in each year that would support the coordinating center responsibilities outlined herein and in other sections of this RFA. In addition, the DCC should request not more than $4,000,000 per year in years 2 through 5 in the Patient Care category for the distribution of approved protocols. The final amount will be determined by NHLBI. These funds will be managed by the DCC and distributed to each participating Clinical Center as a fee for service arrangement after a protocol has been approved and the NHLBI has released the funds for distribution. A half-time position should be budgeted to cover costs associated with the management and distribution of approved protocol dollars to each SCD CRN for all five years. The budget justification for each year must include a table that apportions the total direct cost request among the following categories: 1) core costs, 2) costs of protocol initiation (per protocol), and 3) costs of protocol support (per protocol). Core costs should include support for essential personnel and facilities and the costs for meetings in Bethesda, Maryland of the Protocol Review Committee (about 10 members, 2 meetings per year) and the DSMB (about 8 members, 3 meetings per year). Costs of protocol initiation should include the costs of expanding the manual of procedures and of developing questionnaires, forms, and database structures. Protocol support costs should include the costs of pharmaceutical handling, data entry and analysis, quality control, and manuscript preparation. The DCC budget must include support for the chair over the 5 years (20% effort needed and travel expenses), and also for 2 site visits made to all the clinical centers during the 5 year interval. The total first year budget request should provide for the organization of all administrative aspects of the SCD CRN and for the development and initiation of one to two protocols. Budget requests for years 2-5 should assume that one additional protocol will be initiated and that 2-4 protocols will be active (i.e., recruiting subjects and collecting data). The funds released for DCC operations in each year will be based in part on the number of protocols actually carried out by the SCD CRN and may be more or less than the budget requested in the application.

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.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant award 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/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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). See Section VI.3. Award Criteria.

Section V. Application Review Information

1. Criteria
No additional criteria are specified other than those cited below.

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 the National Heart, Lung and Blood Institute, Division of Extramural Affairs, Review Branch in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

3. Merit Review Criteria

Review Criteria For Clinical Centers

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 work that by its nature is not innovative but is essential to move a field forward.

1. 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?

2. 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?

3. 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?

4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Review Criteria for Patient Outcomes Core

In addition to the standard NIH Review Criteria listed above, the following additional Review Criteria will be used to evaluate application for the Patient Outcomes Core.

1. Potential to develop and validate sickle cell disease specific measures

2. Potential to create a database that can be linked with a patient registry and other databases

3. Potential to provide high quality data that will be used to measure the functioning and well being of patients, or help demonstrate effectiveness of medical interventions.

Review Criteria For Data Coordinating Center

For evaluation purposes of DCC Applications, the following technical criteria will be considered by the Review Committee in the order of relative importance:

1. Personnel: Documented training, expertise, experience, and availability of the Principal Investigator for planning and directing the Data Coordinating Center. Expertise of personnel in preparation of data forms, electronic transmission of data, data management, and biostatistics. Experience of personnel in coordination of multi- center clinical research projects. Documented training, experience, competence, and availability of administrative staff. Documented experience and availability of proposed personnel for website development and maintenance.

2. Methods and Procedures: Merit of the proposed plans for Consortium coordination and for data collection, processing, entry, transmission, storage, statistical analysis, and reporting. Merit of proposed plans for training of CC personnel in data collection and handling. Merit of quality control and quality assurance plans and proposed monitoring of CC performance. Adequacy of plans for protecting the privacy of research subjects.

3. Facilities and Organizations: Availability and adequacy of the facilities and resources necessary to carry out the proposed functions of the DCC. Adequacy of the organizational and administrative structure, including the means of assuring quality control of data, data entry, confidentiality of data, and plans for day-to-day coordination. Institutional commitment to the DCC.

3.A. Additional Review Criteria:

In addition to the above criteria, the following items will 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, http://grants.nih.gov/grants/funding/phs398/phs398.html)

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS 398 research grant application instructions (rev. 9/2004) will be assessed.

3.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.

3.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 funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

3.D. Sharing Research Resources

NIH policy requires that grant award 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/archive/archive/grants/policy/nihgps_2003/index.htm 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

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 Principal Investigator 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. Award Criteria.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

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

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The notice of award signed by the grants management officer is the authorizing document.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

The Notice of Grant Award will be mailed electronically if possible to the authorized business official of the applicant institution.

2. Administrative Requirements

All NIH Grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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/archive/grants/policy/nihgps_2003/index.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 cooperative agreement is an award instrument establishing an “assistance" relationship (in contrast to an "acquisition" relationship) between NHLBI and a recipient, in which substantial NHLBI scientific and/or programmatic involvement with the recipient is anticipated during performance of the activity. The purpose of NHLBI involvement is to support and/or stimulate the recipient's activity by acting as a "partner", while avoiding a dominant role, direction, or prime responsibility. The terms and conditions below, elaborate on these actions and responsibilities, and the awardee agrees to these collaborative actions with the NHLBI Project Scientist to achieve the project objectives. It is anticipated that these terms and conditions will enhance the relationship between the NHLBI staff and the principal investigator(s), and will facilitate the successful conduct and completion of the study. These agreements will be in addition to, and not in lieu of, the relevant NIH procedures for grants administration. The terms will be as follows:

The awardee(s) will have lead responsibilities in all aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.

Clinical Centers.

The NHLBI Project Scientist will serve on the Steering Committee; he/she or other NHLBI scientists may serve on other study committees, when appropriate. The NHLBI Project Scientist (and other NHLBI scientists) may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g., recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and possible changes in protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment.

Awardee(s) agree to the governance of the study through a Steering Committee. Voting members of the Steering Committee will include the Principal investigator from each Clinical Center (or designated alternate), the Principal Investigator from the Data Coordinating Center (or designated alternate), the NHLBI Project Scientist, and a chair appointed by the NHLBI. Meetings of the Steering Committee will ordinarily be held by telephone conference call or in the metropolitan Washington Area.

A Data and Safety Monitoring Board will be appointed by the Director, NHLBI to provide overall monitoring of interim data and safety issues; the Steering Committee will nominate members for this Board. Meetings of the Data and Safety Monitoring Board will ordinarily be held in Bethesda. An NHLBI scientist other than the NHLBI Project Scientist shall serve as Executive Secretary to the Board.

An independent Protocol Review Committee, established by the NHLBI, will provide peer review for each network protocol. Because the Board serves as an independent group advisory to the NHLBI, study investigators will not communicate with Board members regarding study issues, except as authorized by the Board's Executive Secretary.

Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The collaborative protocol and governance policies will call for the continued submission of data centrally to the coordinating center for a collaborative database; the submittal of copies of the collaborative datasets to each principal investigator upon completion of the study; procedures for data analysis, reporting and publication; and procedures to protect and ensure the privacy of medical and genetic data and records of individuals. The NHLBI Project Scientist, on behalf of the NHLBI, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.

Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NHLBI support; or special access to study results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and governance. Within three years of the end of the period of NHLBI support for the project, data not previously released and other study materials or products not previously distributed, are to be made available to individuals who are not study investigators, provided such release is consistent with the study protocol and governance and with paragraph 6. In addition, study investigators must establish a plan for making data sets and materials available to the scientific community and to the NHLBI immediately upon completion of the three year period following the end of the period of NHLBI support.

The NHLBI reserves the right to terminate or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol, (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control, (c) major breach of the protocol or substantive changes in the agreed-upon protocol with which NHLBI cannot concur, (d) attaining of a major study endpoint before schedule with persuasive statistical significance, or (e) human subject ethical issues that may dictate a premature termination.

Upon completion of the project, awardees are expected to put their intervention materials and procedure manuals into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NHLBI, for the conduct of research at no charge other than the costs of reproduction and distribution.

Any disagreement that may arise in scientific/programmatic matters (within the scope of the award), between award recipients and the NHLBI may be brought to arbitration. An arbitration panel will be composed of three members--one selected by the Steering Committee (with the NHLBI member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by NHLBI, and the third member selected by the two prior members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, Subpart D and HHS regulation at 45 CFR part 16, or the rights of NHLBI under applicable statutes, regulations and terms of the award.

These 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 part 74, and other HHS, PHS, and NIH grant administration policy statements.

3. Award Criteria

The following will be considered in making funding decisions:

4. 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:

R. Blaine Moore Ph.D.
Director, Blood Diseases Program
Division of Blood Diseases and Resources
National Heart, Lung and Blood Institute
6701 Rockledge Dr., Rm 10162, MSC 7950
Bethesda, MD 20892 (20817 for express/courier delivery)
Telephone: (301) 435-0080
FAX: (301) 480-0868
Email: mooreb@nih.gov

2. Peer Review Contacts:

Valerie L. Prenger Ph.D.
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
6701 Rockledge Dr., Rm 7214, MSC 7924
Bethesda, MD 20892-7924 (20817 for express/courier delivery)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: prengerv@nhlbi.nih.gov

3. Financial or Grants Management Contacts:

Mr. Robert Vinson
Grants Operation Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
6701 Rockledge Dr., Room 7154
Bethesda, MD 20892 (20817 express/courier delivery)
Telephone: (301) 435-0171
FAX: (301) 480-3310
Email: vinsonr@nhlbi.nih.gov

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity, and dose-finding studies (phase I); efficacy studies (Phase II) efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 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, 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.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at 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 (see 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.

Public 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 public 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 PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.