Bethesda, Maryland

JUNE 4, 2007


Dr. F. Daniel Armstrong, University of Miami, Dr. Micheal Bender, Fred Hutchinson Cancer Research Center, Dr. Johnson Haynes, University of South Alabama, Mobile, Dr. Frans Kuypers, Children’s Hospital of Oakland Research Institute, Dr. Punam Malik, Cincinnati Children’s Hospital Medical Center, Dr. David McCune, Madigan Army Medical Center, Tacoma, WA, Dr. Marie Mann, HRSA, Ms. Shirley Miller Southwestern Comprehensive Sickle Cell Center, Dallas, Dr. Dorothy Moore, Dr. Eugene Orringer, University of North Carolina at Chapel Hill.


Dr. Michael DeBaun, Washington University, St. Louis, Dr. Joseph DeSimone, Veteran’s Administration, Chicago.


Dr. Lanetta Bronte, Memorial Regional Hospital, Hollywood, FLA, Dr. Jonathan Stocker, Icagen, NC, Dr. William P. Winter, Howard University, Dr. Willarda Edwards, President and CEO, SCDAA, Baltimore, Ms. Sonya Ross, SCDAA, Inc., Dr. Onyinye C. Onyekwere, Howard University.


Dr. Susan Shurin, Deputy Director, NHLBI, Dr. Charles Peterson, Director, DBDR, Dr. Greg Evans, BDP,DBDR, Dr. Ellen Werner, BDP,DBDR, Dr. Katherine Hassell, University of Colorado (IPA with NHLBI), DBDR, Ms. Judy Hagopian, HRSA, Ms. Annie Joseph, Committee Management, DEA, NHLBI, Dr. Terry Bishop, NIDDK.


Dr. Marie Early, Centers for Disease Control, Atlanta

Executive Secretary: Dr. Blaine Moore, with assistance from Ms. Petronella A. Barrow.


Dr. Blaine Moore called the meeting to order at 8:30 am, welcomed everyone and provided brief remarks regarding the agenda. He informed everyone of the conflict of interest rules. Dr. Moore turned the meeting over to Dr. Armstrong, the chair of the committee.

Dr. Armstrong requested approval of the minutes from the November 6, 2006 meeting. Some changes to the members list were recommended. (Dr. Malik and Dr. Smith-Whitley were not members at the time of the meeting). Committee attendees were asked to introduce themselves.

Dr Shurin, Deputy Director of NHLBI, welcomed everyone. She discussed the strategic planning report from NHLBI. The plan consisted of three components, a basic science component, a clinical science component and a community component. These three components are integrated. She stated that NHLBI needed to ensure that our research impacts the care of patients. NHLBI has made strides with new born antibiotics and transfusion therapy but we can do better. There are three core values: 1. to be profoundly dedicated to investigator initiated research and to facilitate this, 2. to partner with other agencies, industry or private groups, and 3. to commit to young investigators by giving them a break on the pay line. Dr. Shurin emphasized our need to counsel with patient advocacy groups. NHLBI has a large number of portfolios and there is a need to improve the infrastructure in our programs. Genome Wide Association studies are costly and we are partnering with outside groups to offset expenses

A question was raised concerning the existence of a loan repayment program. Dr Shurin replied that NIH has multiple programs for loan repayment. The NHLBI program is similar to that at NCI. Other members of the committee expressed their appreciation of how NIH contacts the institute and seeks eligible candidates for this program. This has been very helpful. Dr. Bishop from the National Institute of Diabetes, Digestive and Kidney (NIDDK) disorders stated that Dr. Rogers, their institute director, has committed 4M dollars to LRP and plans to increase this next year.

The committee noted that Congress is proposing a 6% increase in the NIH budget for the year. The committee asked what it could do to emphasize the importance of this budget increase. It was raised that the ASH strategic plan acknowledged the lack of sickle cell research and hopes to show more interest in this field. Also, there are a number of organizations that can speak to congress such as ASH, AAP and perhaps the SCDAA. Each year there is a Public Interest Organization meeting in February where patient advocacy groups get together and discuss strategies of growth and development, fundraising, and promoting their disease before congress.

The committee suggested that it would be worth evaluating what NIH has invested in sickle cell research over the last 35 years and what we are doing now. What has been the impact of the research that has been conducted? Currently, the centers are on target for increasing the funds needed to continue its mission since research continues to be more expensive. It was agreed that this is an exciting time in sickle cell research but unfortunately there are limited funds. Dr. Werner, of the Division of Blood Diseases at NHLBI is initiating a consensus conference on the use of hydroxyurea in sickle cell disease. In doing this we are connecting with HRSA and AHRQ representatives. She noted that the evaluation must be unbiased and that panel members on the consensus conference must not have conflicts in SCD.


Dr. Ellen Werner of the Blood Division introduced the first speaker, Dr. Lanetta Bronte. Dr. Bronte is with the Memorial Regional Hospital in Hollywood, Florida. She discussed the challenges in creating, developing and maintaining a sickle cell day hospital that is certified by the Joint Commission Disease-specific Care Program. The hospital consists of 4 adult and 5 pediatric hematology/oncology physicians, a nurse practitioner, a social worker and a specialty care coordinator. The day hospital has developed evidenced-based clinical practice guidelines, acts as a training resource and participates in clinical research. Dr. Bronte discussed the performance measures that are required to receive certification by the Joint Commission.

Dr. Greg Evans of the Blood Division introduced the second speaker, Dr. Jonathon Stocker, from ICAGen. He discussed the challenges of conducting phase II and phase III clinical trials in sickle cell disease. Recently, ICAGen has been involved in conducting an interventional drug trial with sickle cell patients. Dr. Stocker discussed the challenges associated with establishing sites and recruiting patients. He proposed that this process could be made easier by tapping into resources such as the Comprehensive Sickle Cell Centers and more importantly the sickle cell community centers which are present across the United States. The committee agreed that this would be useful and would make a recommendation to that effect.


  • HRSA (Dr. Marie Mann)

    A SCD Treatment Demonstration Program is currently funded by the Talent Bill passed by Congress. There are 4 sites developing performance measures for this program. Among these measures, some are using the American Home Model, a model which has been accepted by several academies and organizations. The supported networks are tailoring their services by defining their performance measures through evidence-based medicine for both pediatric and adult SCD patients. One of the goals is to look at long-term follow-up of sickle cell subjects, particularly within the southeast region. Another goal is to bring professionals to work with the patients on a more personal basis. A piloting program is underway to study the transitioning of patients from pediatric to adult care. Dr. Mann suggested that the development of databases and/or registries for SCD may be able to collaborate with institutes such as NICHD who have funding for this. Dr. Shurin indicated that we are currently interacting with members at NICHD for this purpose. . The NHLBI approach is to partner with other resources, other institutes and other agencies. These databases and registries are only as good as they are useful for the facilitation of other programs. Hence it is necessary to carefully craft the outcomes and measures to be acquired. Finally, HRSA supports regional centers for new born screening programs for sickle cell disease.

  • DEPARTMENT OF THE ARMY (David McCune from Seattle)

    Sickle Cell Disease is excluded from the armed forces but sickle cell trait persons are included. The army would like to participate more in clinical studies. His contact information is in the packet. The Army is the largest branch of the armed forces and can involve other branches to identify candidates eligible for studies.

  • DBDR DIRECTOR REPORT (Dr. Charles Peterson)

    DBDR is aiming to make the strategic plan relevant to Blood and specifically SCD. This committee will play an important role. This is necessary to keep what we do vibrant. Dr. Peterson thanked the committee members (Dr. Johnson Haynes, Dr. Michael DeBaun and Dr. Dorothy Moore) who have completed their 3 years on the committee. He presented to them certificates and letters from Dr. Betsy Nabel, the Institute Director thanking them for their service.

  • REPORT FROM NIDDK (Dr. Terry Bishop)

    The NIDDK Hematology Program continues to fund R01s and R21s in Sickle Cell Disease. These applications are predominantly in globin transcription and erythropoiesis. Currently some of the applications are going through the RAID program which is used for preclinical work for new drugs. NHLBI and NIDDK continue to support these together. NIDDK also supports Training and Career Development awards as well as loan repayment awards for investigators studying SCD research. NIH is very interested in supporting in New Investigators. NIDDK is organizing a planning meeting in SCD to assess what areas are being under supported.


    Comprehensive Sickle Cell Centers (Dr. Greg Evans)

    The review meeting for the open re-competing renewal of the Comprehensive Sickle Cell Centers (CSCCs) will take place September 5th to 7th in 2007. In response to a request from the committee at the last meeting, Dr. Evans showed the overall annual program budget numbers for the NHLBI sickle cell centers from 1972 to date (including a projection for fiscal year 2008, with no correction for inflation. The budget has gone up significantly since 1972, it went up significantly during the NIH doubling period of 1999-2004, and is expected to be relatively flat next year over this year, much like the rest of the NIH. In 1998, a Data Coordinating Center was added as a subcontract to one center in order to begin to facilitate collaborative clinical trials among the 10 centers. In 2003, a fully independent Data Coordinating Center and formal clinical trial consortium were added to the CSCC program. At present the collaborative clinical trials going on include: an oral Arginine supplementation study, a neurocognitive function study with MRI imaging, a clinical database study (known as the Collaborate Data Project), a study on the epidemiology of priapism, the CHAMPS (magnesium plus hydroxyurea combination therapy) study, a Genotype/Phenotype study (DNA collection, genotyping, and red cell characterization linked to the Collaborative Data Project), and a study of oral dexamethasone for acute chest syndrome (ACS). The Steering Committee has recently voted to defer two additional studies under development to the next funding cycle that begins in April 2008. They are a study of subcutaneous decitabine for fetal hemoglobin induction and a study of oral methadone for management of chronic pain. The intent is for the last two to be presented as fully developed, DSMB-approved protocols that can be considered for possible implementation by the Steering Committee for the next cycle. The CSCC program includes significant research training and education activities, including a Scholar component for training of junior faculty, training supplement program that involves students from high school up to the junior faculty level, and a Sickle Cell Summer for Science program focused on high school students in the summer.

    One committee member asked if clinical care is better for patients at CSCCs as opposed to other clinical sites. Other committee members responded by saying that there is limited information to answer that question and it depends what parameters are used for measuring success. Generally, physicians in the community often refer patients to the closest CSCC where possible.

    SICKLE CELL DISEASE – CLINICAL RESEARCH NETWORK (SCD CRN) (Dr. Harvey Luksenburg) The Sickle Cell Disease Clinical Research Network was initiated in April, 2005. The network consists of 8 clinical centers and a Data Coordinating Center (New England Research Institute) whose purpose is to conduct phase II and Phase III clinical studies relevant to sickle cell disease. Dr. Peter Lane is the current chair of the Steering Committee and Dr. Carlton Dampier is the co-chair. At present they are developing two phase III clinical studies. These are:

    • Preventing Acute Chest Syndrome by Transfusion Trial, “PROACTIVE”.
    • Renoprotective Effect of Angiotension II Blockade with Losartan in Albuminuric Patients with Sickle Cell Nephropathy.

    In addition, the Network is actively considering co-sponsorship of the following two studies, submitted by outside groups:

    • Transfusion Alternatives Pre-Operatively in Sickle Cell Disease (TAPS) (National Blood Service, United Kingdom)
    • Unrelated Donor Hematopoietic Transplantation for Children With Sever Sickle Cell Disease Using a Reduced Intensity Conditioning Regimen (Bone Marrow Transplantation Clinical Research Network)


    The purposes of the Patient Outcomes Cores (POC) are to:

    • Conduct, and collaborate with sites on pharmacoepidemiology, Phase IV, or health economic studies
    • Conduct and collaborate with sites on behavioral, psychosocial, and health services and outcomes studies.
    • Develop or evaluate instruments, such as questionnaires, and support RCTs.

    The first study completed compared inpatient outcomes between sickle cell disease and non-sickle cell disease patients undergoing high-volume surgical procedures.


    The purpose of this contract is to develop, validate, and disseminate an SCD HRQoL measurement information system for use with adults in clinical research and patient care; to test the validity of PROMIS among adults with SCD; and to develop SCD-specific content for use in conjunction with PROMIS.

    The objectives of the project are:

    • Phase 1: To determine content that should be included in the SCHRe-QoL, and to ensure that it is useful for describing the impact of SCD and its treatments on adult patients.
    • Phase 2: To field test SCHRe-QoL to determine its reliability and utility for clinical and community studies in adults with SCD.
    • Phase 3: To disseminate SCHRe-QoL and supporting documentation to the clinical research community, and provide early users with technical support.

    Over 1,197 critical incidents have been collected from 135 adult patients and 15 SCD health care providers. These incidents fell into the following categories: (1) Emotions; (2) Attitudes and Beliefs; (3) Family and Social Relationships; (4) Morbidities and Co-Morbidities; (5) Sexuality and Reproduction; (6) Medical Care; (7) Health Insurance; (8) Employment; (9) Education; (10) Faith/Spirituality; (11) Altruism; (12) Stress/Control/Predictability; (13) Activity Limitations; (14) Housing and (15) Community. Sub-categories further described the ways a person's life is affected by SCD and its treatment.

    This taxonomy is a comprehensive model of issues that affect adult patients with SCD. It includes well-being and functioning, which are HRQOL outcomes, and non-HRQOL issues including patient preferences, satisfaction with and access to care.

    K12 TRAINING PROGRAM (Dr. Ellen Werner)

    The purpose of this Program is to develop and evaluate multidisciplinary career development programs in non-malignant hematology that will equip new investigators with the knowledge and skills to address complex problems in blood diseases. Through this Program, the NHLBI will support the early career development of clinical researchers who are expected to become independent investigators and assume academic leadership roles in non-malignant clinical hematology. Six sites have been awarded grants to conduct this training. The sites include:

    • Harvard Medical School, Dr. Ellis Neufeld, PI
    • University of Pennsylvania, Dr. Barbara Konkle, PI
    • Duke University/University of North Carolina, Dr. Marilyn Telen, PI
    • Johns Hopkins University, Dr. James Casella, PI
    • University of Washington, Dr. Janis Abkowitz, PI
    • Washington University St. Louis, Dr. Evan Sadler, PI


    On September 14-15 2006, the NHLBI convened a Working Group to develop health objectives for people with SCD. The working Group was charged with identifying health priorities for SCD that should be used to drive and prioritize subsequent efforts, and that should include appropriate measures by which to evaluate efforts.

    This NHLBI working group is the beginning of an effort to help the SCD research, provider, and patient community catch up with national efforts by specifying health objectives for people with SCD throughout the lifespan.

    The SCD objectives were organized into 4 topics:

  • Health Status: objectives related to physical and medical status, life expectancy, quality of life, and functioning.
  • Health Promotion: objectives related to activities to prevent complications, self-management, health behaviors, health education, and reduction of risk behaviors. [It also includes social support systems, patient knowledge, and coping.]
  • Health Services: objectives related primary and specialized health services, medical tests, access to health care, and emergency services.
  • Health Workforce: objectives related to the availability of a wide range of health care providers and their skills and knowledge of SCD.

    The full report is available on the NHLBI website, http://www.nhlbi.nih.gov/meetings/workshops/scd-healthobj.htm


    The purpose of a surveillance system is to generate data on the prevalence of hemoglobin disorders, including SCD, the demographics of patients, and other data elements. NHLBI is taking the lead to examine the possibility of planning, designing and implementing a federal surveillance system in hemoglobinopathies. In August 2007, NHLBI will convene a Working Group of federal scientists to discuss federal data systems, health statistics, logistics for launching a new system, hemoglobinopathies and clinically significant genotypes budgets, data linkage, and other relevant issues. This working group is the first step in the planning phase. More Working Groups will be held in 2007 and 2008 to continue the planning. NHLBI plans to present a detailed and realistic initiative to the NHLBI's Board of External Experts and Advisory Council later in 2008.


    Dr. Kathy Hassell spoke as representative of the Sickle Cell Adult Provider Network (SCAPN). The network is evaluating the best practices for assessing and treating adult sickle cell disease. The first conference was held in September, 2006 and focused on pain management in the emergency department, inpatient and outpatients settings. SCAPN holds an annual symposium to discuss many of these issues. The next meeting will be held during the up-coming sickle cell meeting in September in Washington, DC and will address transfusion practices and chelation therapy in adults with sickle cell disease.

    BABY HUG PHASE 3 CLINICAL TRIAL (Dr. Charles Peterson)

    The primary objectives of this multi-center trial are to determine if hydroxyurea can prevent damage to kidneys and spleens of infants with sickle cell disease. The trial consists of 14 clinical centers headed up by Dr. Winfred Wang of St. Jude Children’s Research Institute and a Data Coordinating Center headed up by Dr. Bruce Thompson of C-TASC. The target enrollment for the trial is 200 patients. Currently, the trial has screened 231 patients and enrolled 179.

    SWITCH PHASE 3 CLINICAL TRIAL (Dr. Harvey Luksenburg)

    SWiTCH is a Phase III clinical trial designed to test the hypothesis that hydroxyurea and phlebotomy can maintain an acceptable stroke recurrence rate and significantly reduce hepatic iron burden in comparison to transfusion plus chelation in children who have had a prior over stroke.

    This trial is expected to accrue 130 subjects. Sixty-five subjects will be randomized to continue to receive periodic transfusion therapy and chelation, and 65 to receive hydroxyurea and undergo phlebotomy. There are two primary endpoints: the occurrence of secondary stroke during the 30 month treatment period, and change in liver iron level between baseline and the end of therapy.

    There are 23 clinical sites, and 22 have been activated thus far. Enrollment began at the end of October, 2006. As of March 1, 2007, 19 subjects have been enrolled, and 10 have been randomized.


    Patient visits have been completed and the investigators are focusing on data analysis and publications. Seventeen formal writing groups have been assembled with individuals identified as primary contacts. Bench marks are being determined for the writing groups depending on the stage that they are in writing the manuscript.


    This is an active RFA that is 4 years in duration that began in 2005. Five grants are currently funded. There are two grants on Pulmonary Hypertension, one grant on asthma, one grant on Acute Chest Syndrome and the role of placental Growth Factor and one grant on hypoxia. Dr. Malik discussed her study on ACS and placental GF. At this time she doesn’t have sufficient funds to expand to a multi-center clinical trial. Grants have both basic and clinical science components.


    This is a contract trial that originated with Dr. Mark Gladwin in intramural NHLBI in July 2004. Subjects aged 12 and up will be screened by echocardiography, and blood and DNA samples will collected and stored in the NHLBI repository for biological specimens. Patients will be randomized to either sildenafil or placebo for 16 weeks. The definition for pulmonary arterial hypertension for study entry has been changed from 2.5 m/sec to 2.7 m/sec for the TRJ velocity measured by echocardiography. Right-heart catheterizations are only being done for patients who have a TRJ velocity above 3 m/sec. Dr. Haynes stated his belief that all patients should be catheterized before going on therapy. Dr Evans stated that this issue has already been discussed extensively by the Steering Committee and DSMB. Dr Hassell added that previous work from Dr Gladwin has shown that a high TRJ velocity alone, without pulmonary artery pressures obtained by cardiac cathetization procedures, is highly correlated with a shortened lifespan. The trial is expecting to recruit 132 patients. The sites involved in this study include: intramural NHLBI; University of Colorado Health Sciences Center; Children’s Hospital, Oakland; University of Illinois, Chicago; Children’s Hospital, Pittsburgh; Howard University; Johns Hopkins University; Albert Einstein College of Medicine; and Hammersmith Hospital, London


      A. Comments from Sickle Cell Disease Association of America Working with NHLBI in organizing the sickle cell combined meeting. Bringing back almost all of the previous poster children. This is a special year because we are now in DC. And we plan to go to the hill during the meeting. Had a wonderful meeting to initiate our registry project. People were there from CDC, NHLBI and HRSA. We are trying not to re-invent the wheel. We are trying to work together to get all the things that everyone wants. We want to make sure that the new born screening program continues with HRSA and so will be contacting congress.

      B. Comments from other public interest organizations


      1. NHLBI, in collaboration with other agencies, will organize and distribute population data on the prevalence of SCD in the United States

      2. NHLBI will prepare a presentation for the next meeting to give possible mechanisms for developing surveillance, patient registry and institutional capacity, data set and discussion about types of registries.

      3. NHLBI will make minutes and other information about the SCDAC Committee available on a public web site.

      4. The Sickle Cell Disease Advisory Committee will develop a strategic plan for sickle cell disease at the National Sickle Cell Convention in September.

    FUTURE MEETING DATES: October 29, 2007; June 2, 2008


    R. Blaine Moore PhD

    CSCC Executive Secretary


    Dr. F. Daniel Armstrong, Chair

    Last updated: October 28, 2007

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