NHLBI Specialized Centers of Clinically Oriented Research (SCCOR) for Sickle Cell Disease is a grant from the National Heart, Lung, and Blood Institute (NHLBI/NIH) that funds a Clinical Research Network of up to 15 clinical centers to design and conduct multiple therapeutic trials for patients with sickle cell disease, along with a Data Coordinating Center and patient outcomes research cores.

The program supports the full spectrum of clinical and translational research aimed at developing new treatments and improving patient outcomes for this inherited blood disorder. Eligible applicants include for-profit and nonprofit organizations, universities, hospitals, laboratories, units of state and local governments, community-based organizations, and faith-based organizations in the United States.

NHLBI intended to commit approximately $36,000,000 in total costs over a 5-year period using a U10 cooperative agreement mechanism.

Expired RFA-HL-05-006: Sickle Cell Disease Clinical Research Network This notice has expired. Check the NIH Guide for active opportunities and notices. 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/ ) Catalog of Federal Domestic Assistance Number(s) 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 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) 710-0267, Email: [email protected] .

Part I Overview Information Part II Full Text of Announcement Section I. Funding Opportunity Description Section II. Award Information 1.

Mechanism(s) of Support Section III. Eligibility Information 3. Other - Special Eligibility Criteria Section IV.

Application and Submission Information 1. Address to Request Application Information 2. Content and Form of Application Submission A.

Receipt and Review and Anticipated Start Dates B. Sending an Application to the NIH C. Application Processing 4.

Intergovernmental Review 6. Other Submission Requirements Section V. Application Review Information 2.

Review and Selection Process A. Additional Review Criteria B. Additional Review Considerations D.

Sharing Research Resources Section VI. Award Administration Information 2. Administrative Requirements A.

Cooperative Agreement Terms and Conditions of Award 1. Principal Investigator Rights and Responsibilities 3. Collaborative Responsibilites 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 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.

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 Development of a linkable database that includes phenotype and genotype.

This database will be coordinated with the current Sickle Cell Disease Centers Program and the Thalassemia Clinical Research Network. Identification of new gene targets and biomarkers for early diagnosis, treatment, and prevention of complications through newer genomic and proteomic techniques using an expanded registry and international outreach as needed.

Development of new treatment for the amelioration and prevention of vaso-occlusive crises. Development of new chelators or agents for treatment of sickle cell disease and thalassemia subjects to combat iron overload resulting from chronic transfusion therapy. Indicate a willingness to participate in the design and implementation of a study of a vaccine against Parvovirus B19 in sickle cell patients.

Participate in studies of the cost effectiveness of therapeutic interventions should the NHLBI choose to implement such research within the SCD CRN. Development of novel therapeutic agents and approaches to safely increase hemoglobin F induction.

Development of novel therapeutic agents to ameliorate or prevent other complications of sickle cell disease such as stroke, avascular necrosis of the hip, acute chest syndrome, pulmonary hypertension and thrombotic events. Determination of the effectiveness of multi-drug therapies that may be appropriate for subsets of patients.

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/grants/policy/nihgps_2003/NIHGPS_Part2. htm . 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. A. Eligible Institutions Institutions may submit (an) application(s) if they have any of the following characteristics: Public or private institutions, such as universities, colleges, hospitals, and laboratories Units of state government Units of local government Eligible agencies of the Federal government Community-based and Faith-based Organizations Foreign institutions are not eligible to apply.

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.

There is no required cost sharing , matching, or cost participation without which an application would be ineligible. http://grants. nih.

gov/grants/policy/nihgps_2003/nihgps_Part2. 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: Participate in Steering Committee meetings (expected to occur approximately 4 times in the first year and 3 times per year in subsequent years in or near Bethesda, Maryland), site visits required by the NHLBI, and regular telephone conference calls Cooperate with other awardees in the development and design of research protocols Abide by common definitions; common methods for patient selection and enrollment; and common protocols, procedures, tests, and reporting forms as chosen by majority vote of the Steering Committee Actively seek to implement each network-wide protocol approved by the Protocol Review Committee and the NHLBI Indicate a willingness to participate in the design and implementation of a study of a vaccine against Parvovirus B19 in sickle cell patients Comply with study policies and quality assurance measures approved by the Steering Committee Agree to oversight of the study by the DSMB Accept awards for the support of research based on per-patient (capitated) rates and the actual numbers of subjects who are enrolled and followed, and who complete each study (Clinical Centers only) Accept awards for the support of research based on the number of protocols developed, initiated, and carried out (Data Coordinating Center only), Transmit study data to the DCC in a timely and accurate manner (Clinical Centers only) Report all adverse events in accordance with procedures established by the Steering Committee and NHLBI policies Cooperate with other awardees and NHLBI in the publication of study results and the eventual release to the scientific community of study procedures and other resources Develop and implement plans for the dissemination of study results to physicians involved in the care of patients with sickle cell disease Participate in studies of the cost effectiveness of therapeutic interventions should the NHLBI choose to implement such research within the SCD CRN, and Accept the Cooperative Agreement Terms and Conditions of Award given below and work in a collaborative and collegial manner to foster the goals of the network 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) 710-0267, Email: [email protected] .

Telecommunications for the hearing impaired: TTY 301-451-5936. 2. Content and Form of Application Submission Applications must be prepared using the 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. 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 Prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed research Name, address, and telephone number of the Principal Investigator Names of other key personnel Participating institutions Number and title of this funding opportunity 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: 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 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: 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 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 . 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 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