Bethesda, Maryland

November 7, 2005


Dr. Marie Earley, Centers for Disease Control, Atlanta; Dr. Daniel Armstrong, University of Miami; Dr. Michael DeBaun, Washington University, St. Louis; Dr. Paul Frenette, Mount Sinai School of Medicine, New York; Dr. Frans Kuypers, Children=s Hospital of Oakland Research Institute, California; Ms. Shirley Miller, Southwestern Comprehensive Sickle Cell Center, Dallas; Dr. Eugene Orringer, University of North Carolina, Chapel Hill; Dr. Theodore Wun, University of California, Davis, Dr. Joseph Desimone, Veterans=s Administration, Chicago; Dr. Marie Mann, Health Resources and Services Administration (HRSA), Bethesda.


Dr. Johnson Haynes, University of South Alabama, Mobile; Dr. Russell Ware, St. Jude Children=s Hospital, Memphis; Dr. Dorothy Moore, Sickle Cell Disease Association of America, New Jersey.


Dr. Robert Sheffler, Trippler Army Medical Center, Washington, D.C.; Dr. William H. Hannon, Centers for Disease Control, Atlanta.


Dr. Greg Evans, DBDR; Ms. Judith Hagopian, HRSA; Dr. Charles Peterson, DBDR; Dr. Ellen Werner; DBDR; Dr. William P. Winter, Howard University; Dr. Terry Bishop, NIDDK/NIH; Dr. Dan Wright, NIDDK/NIH; Dr. San Keller, American Institute for Research, Washington, D.C.; Dr. Wally Smith, Virginia Commonwealth University; Ms. Angela Mason, Sickle Cell Disease Association of America, Baltimore; Dr. Kathy Robie Suh, Food and Drug Administration, Rockville; Dr. Debra Ader, NIAMS/NIH; Dr. Bryce Reeve, NCI/NIH.

Acting Executive Secretary Dr. Greg Evans, with assistance from Ms. Petronella A. Barrow

Dr. Greg Evans called the meeting to order at 8:40 a.m. and led the introductions of members and guests.

  1. Dr. Ted Wun called for review of the minutes of June 6, 2005. Dr. Wun asked that the minutes be revised to include Dr. Ware=s written comments (made after the last meeting) cautioning against requiring both pediatric and adult clinics in the next Comprehensive Sickle Cell Center RFA. Forced addition of adult care to a strong pediatric center may result in an overall decline in work quality. Dr. Mann requested that a correction be made to the June minutes to reflect that HRSA recently awarded grants to 17 community and state-based SCD newborn screening projects and funded the Sickle Cell Disease Association of America (SCDAA) to serve as the coordinating center for the projects. HRSA is also working with the Comprehensive Sickle Cell Centers and SCDAA to facilitate education, counseling, and follow-up efforts. With these two changes, the June minutes were approved unanimously.
  2. Dr. Wun welcomed members and guests, and Dr. Ellen Werner introduced the Scientific Presentations.

    A. NHLBI Sickle Cell Disease Health-Related Quality of Life Questionnaire Development Project- Dr. San Keller, American Institute for Research

    Dr. Keller described this new NHLBI-funded contract project to develop a sickle cell disease-specific instrument for measuring health-related quality of life in adult sickle cell disease patients. She contrasted health-related quality of life with quality of life, pointed out the advantages of patient-reported health data in clinical trials, and described the time line for the new NHLBI project. There will be three phases over three years: I- formative research to support prototype methods and products; II- data collection and analysis to produce beta versions of methods and products; and III- evaluation and modification of beta versions in response to real world application. Dr. Keller also described in brief an ongoing NIH Roadmap effort on a Patient Reported Outcomes Measurement Information System (PROMIS). This will be a resource with methods and data covering general health, physical functioning, societal role functioning, cognitive functioning, emotional functioning, pain, fatigue and sexual functioning. PROMIS will be accessible to all NIH-sponsored researchers and unlike the new NHLBI project, will include children. The discussion by the committee was focused on the need to be aware that some patients may be unable to answer all questions in the new NHLBI project, that poverty may be a big contributor to well being, and that the FDA will soon publish a guidance document on the use of health-related quality of life measures in clinical trials.

    B. NHLBI PISCES (Pain in Sickle Cell Epidemiology Study) Project- Dr. Wally Smith, Virginia Commonwealth University.

    Dr. Smith described his recently concluded NHLBI R01 project designed to measure in adult sickle cell patients the variability, severity, and response to sickle cell pain, and to build predictive models for patient behavior in response to pain.

    There were 226 compliant patients in the study, 56% had some pain based on patient diaries, and 26% had pain every day. 30% reported severe pain (chronic pain syndrome), and only 13% had pain on 5% of days or less. Importantly, more common pain was correlated with higher pain intensity. In addition, health care utilization did not accurately reflect pain. Patients with the hemoglobin SS genotype had pain more frequently than SC patients, as expected. The knees, thigh, and shoulder were the most common sites of pain. Overall, the quality of life of patients in this study was deemed to be about the same as that for dialysis patients, and worse than that for asthma patients. 28% of patients reported depression, and 31% reported alcohol abuse. These results are being prepared for publication.

  3. Chairman's Report. Dr Wun provided an update on the Sickle Cell Adult Provider Network now in development. This group of physicians was formed after an NHLBI Working Group on the same topic about one year ago. The goal is to provide expert medical advice on sickle cell issues to physicians around the country in real time. This group met in Cincinnati in April of this year as part of the National Sickle Cell Program meeting, and will integrate with the program in Memphis next April. They will also meet at ASH next month. There is no firm structure yet, but the group is fielding questions on an e-mail listserv. This is a grass roots effort among providers. There is a small project planned to reach out to emergency medicine specialists regarding emergency department care for sickle cell patients, and Kathy Hassell is planning a cross-sectional survey regarding adult stroke. The website for this network has information on its mission statement, and a compilation of cases (e.g. liver transplants in sickle cell disease), and an upcoming events section.

  4. Agency Reports

    A. CDC. Dr. Marie Earley reoprted that on December 1 she will take over the CDC newborn screening program from Dr. Barbara Adam. There are currently 74 participants,and four- Brazil, India, Spain, and the U.K.- are on the waiting list. All participating labs look for hemoglobin S, C, D, and E variants.

    B. HRSA. Dr. Marie Mann reported that HRSA is funding a newborn screening reference lab at Children=s Hospital, Oakland. This funding will expire soon. New Hampshire has recently added newborn screening for hemoglobin variants. Now all 50 states have newborn screening for common hemoglobin variants. There was recently a new round of HRSA grants for newborn screening centers, 8-9 new ones, with one year of funding. HRSA will soon partner with SCDAA on a genetic counseling certification program. Regarding the status of the Talent bill, the Senate has recently approved $2 million in funding for FY2006. The House has not yet acted.

    C. Veterans Administration. Dr. Joe DeSimone reported that minority-targeted programs are being looked at carefully right now with an eye toward budget cutting. These are not a funding priority for VA at present.

  5. DBDR Director's Report. Dr. Charles Peterson reviewed NHLBI budget projections for FY2006. The NIH is on a continuing budget resolution right now, and a final FY2006 budget may be passed before Christmas. Current draft budgets call for a year to year decrease in FY2006 of across the NIH and other federal agencies. The NHLBI is responding to this anticipated budget by setting a special, higher payline for young and new investigators. NHLBI, DBDR will do the best it can to protect its core programs during this budget situation. NHLBI is embarking on a strategic planning exercise across the Institute. This will take place over the next two years two years, and it is just beginning. This committee will be kept apprised of future developments in this area.

  6. Update on Program Activities

    A. The NHLBI Strategic Plan for Hemoglobin Disorders. This plan was described in full in the June 2005 minutes. Dr. Evans gave an update on three recent activities under this plan. First, the NHLBI co-funded with NHGRI an RFA on chemical genomics with applications to sickle cell disease. Three projects were funded for two years. Second, the NHLBI convened a Working Group on gene therapy for hemoglobin disorders on June 28. The purpose was to discuss a plan and time line for the first clinical trials in this area in the U.S. The report from this meeting was recently completed, and Dr. Evans will distribute the report to the committee forthwith. Third, the NHLBI convened a Working Group on drug development for hemoglobin disorders on September 20. The purpose of this meeting was to discuss barriers to drug development, and the report will be distributed to the committee when available.

    B. Comprehensive Sickle Cell Centers Update. Dr. Evans listed and reviewed the progress made by the CSCC program on collaborative clinical trials. The eight active and proposed trials are as follows:

    • Oral arginine supplementation in children and adults to stimulate the nitric oxide pathway and improve red cell hydration.
    • Neurocognitive function, neuroimaging, and transfusion in adults.
    • The Collaborative Data registry and DNA/plasma repository (all CSCC patients).
    • The epidemiology of priapism in children and adults.
    • Hydroxyurea plus magnesium in adult and pediatric hemoglobin SC patients to improve red cell hydration.
    • Dexamethasone for Acute Chest Syndrome in children and adults.
    • Phase II study of decitabine for fetal hemoglobin induction in adults.
    • Oral methadone for stable pain control in children and adults.

    Dr. Evans also mentioned that the next RFA for this program should be published early in 2006. Dr. Debaun asked if the trials listed above could also be listed in the next RFA so that applicants are aware of the nature of collaborative clinical trials from the prior funding cycle.

    C. MSH Patients Follow-up. In Dr. Bonds absence, Dr. Orringer, who participates in this study, noted that this is an epidemiological follow-up study for adult patients who have been treated with Hydroxyurea. Current plans include following up with the offspring of MSH patients to study teratogenicity and to conduct CT (computed tomography) scans of the chest in all patients to look for evidence of chronic lung damage from acute chest syndrome, pulmonary embolism, or chronic pulmonary disease. This project has committed funding for two more years.

    D. Health-Related Quality of Life. Dr. Werner reported that this project (described in the scientific presentations today- see above) is underway, and is expected to last for three years.

    E. Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). In Dr. Bonds=s absence, Dr. Armstrong, a participant in this study, reported that the pilot phase of this trial has now completed enrollment (40 patients), though the complete results of the pilot trial will not be known for at least two years. The full trial is underway.

  7. Suggestions for NHLBI from the Committee

    Two motions were moved, seconded and approved as recommendations from the SCDAC to NHLBI:

    1) The first motion was to recommend continued financial support from federal agencies for a reference laboratory to perform hemoglobin diagnosis for rare variants. This could be a partnership between NIH, CDC, HRSA, and industry.

    2) The second motion was to recommend that the development of a health-related quality of life instrument be extended by NHLBI in the future to include children. Together with the adult project, this would provide such instruments for use in any large adult or pediatric clinical trial for sickle cell disease.

  8. Dates of Next Meetings
  9. June 5, 2006

    November 6, 2006

    The meeting adjourned at 1:00 p.m.

    These minutes are hereby approved.

    ___________________________                                    _____________
    Theodore Wun, M.D.                                                   Date
    Sickle Cell Disease Advisory Committee

    ___________________________                                     ______________
    Greg Evans, Ph.D                                                        Date
    Acting Executive Secretary
    Sickle Cell Disease Advisory Committee

    Last updated: October 28, 2007

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