MINUTES OF THE SEVENTY-FOURTH MEETING OF THE SICKLE CELL DISEASE ADVISORY COMMITTEE Bethesda, Maryland June 8, 1998 COMMITTEE MEMBERS PRESENT Dr. Kenneth Bridges, Dr. Iris Buchanan, Dr. Jessica Davis, Dr. Joseph DeSimone, Dr. James Eckman, Dr. Mary Fabry, Dr. Vipul Mankad, Dr. William Mentzer, Ms. Sonya Ross EX-OFFICIO MEMBERS PRESENT Dr. Michele Puryear, Dr. Martin Steinberg EX-OFFICIO MEMBERS ABSENT Dr. Scott Wegner, Dr. William Hannon PROGRAM STAFF AND AFFILIATED ORGANIZATION REPRESENTATIVES: Dr. Clarice D. Reid, DBDR; Dr. Carol H. Letendre, DBDR; Dr. Duane Bonds, SCDSRG; Dr. Charles Peterson, BDP, DBDR; Ms. Susan Pucie, DBDR; Ms. Marie Mann, MCHB/HRSA; Ms. Patricia Penn, Maryland, DHMH, Office of Hereditary Diseases; Dr. Oswaldo Castro, Howard University; Ms. Lisa Douglas, Georgetown University, Dr. Margaret Chesney, UCSF; Robin Gill, DECA, Dr. Ramesh Vemuri, NHLBI, Dr. Junius Adams, III, Howard University, Dr. William Winter, Howard University, Pat Pearl, CHMC/ Cincinnati Sickle Cell Center Executive Secretary - Dr. Duane R. Bonds Secretary - Ms. Petronella A. Barrow I. INTRODUCTORY REMARKS Dr. William Mentzer, Chairman, called the 74th meeting of the Sickle Cell Disease Advisory Committee to order at 9:00 am. II. ANNOUNCEMENTS Dr. Clarice Reid, Director of the Division of Blood Diseases and Resources (DBDR), read the mandatory conflict of interest statement and reminded members to sign and return their forms to Ms. Barrow. She noted that Ms. Sonya Ross is now an official member of the committee from the State of Maryland Department of Health and Mental Hygiene, Office of Hereditary Disorders. Two graduating members from the committee were congratulated: Dr. James Eckman and Dr. Mary Fabry. III. CONSIDERATION OF MINUTES The minutes of the last meeting were approved unanimously. IV. CHAIRMAN'S REPORT Dr. Mentzer announced that the next meeting of the National Sickle Cell Disease Program will be held in San Francisco on March 6-9, 1999. The chairman also issued a charge to the committee to consider new initiatives and new directions for the sickle cell disease program to consider. V. DIRECTOR'S REPORT Dr. Reid, Director of DBDR, announced the appointment of the two new program directors: Dr. Charles Peterson, Director of the Blood Diseases Program, and Dr. Henry Chang, Director of the Blood Resources Program. The administrative staff of the Institute has now been consolidated into one area and physical space has been lost to the Sleep Center. In discussing the budget, Dr. Reid indicated that the NIH received a 7.7% increase over last year's budget. Plans are currently under development to consider options for the use of this increase including paying more grants by increasing the payline, and identification of research opportunities under the 7 areas of emphasis outlined by Dr. Varmus. NIH has instituted 3 new training mechanisms in the area of clinical research: the K-23 which is a mentored patient-oriented research career development award; the K-24 which is a mid-career investigator award in patient-oriented research; and the K-30 which is an institutional grant for curriculum development. The celebration of the NHLBI 25th anniversary is well under way. At the last meeting of the NHLBI Advisory Council, the 3 high school students who produced prize winning posters to be used for education about heart, lung and blood diseases were introduced. There will be a mini-medical school symposium at the Smithsonian Institute in June at which Dr. Cage Johnson, former chair of this committee will present a short course on sickle cell disease. Dr. Reid presented the upcoming workshops and proposed initiatives to the committee. Of particular interest is the Managed Care for Hemoglobinopathies Workshop scheduled for August 25, 1998 here in Bethesda. In addition, the report of the task force on Behavioral Research was presented. VI. SCIENTIFIC PRESENTATIONS Opportunities for Behavioral Research in Blood Diseases - Dr. Margaret Chesney, Professor of Medicine, University of California at San Francisco Dr. Chesney reported on the task force that was called to review the progress and needs for behavioral research in heart, lung, blood diseases and sleep disorders. The committee was asked to describe behavioral aspects of sickle cell disease. Patients with sickle cell disease feel stigmatized, and therefore are reluctant to share with others that they have the disorder. Thalassemia patients, especially when they reach adolescence, are uncomfortable around their peers because they wear chelation pumps. Adherence to medical care is a problem for all chronic disorders, which should stimulate compliance research in the Blood Division. The reaction of health care providers to individuals with chronic and acute pain has also proved to be an area of concern with sickle cell disease patients bearing the stigma of 'drug seeking behavior'. Recent pain research suggests that sickle cell disease pain should be managed in a similar fashion to cancer pain, and this information needs to be more widely disseminated to the physicians who see sickle cell disease patients, especially in emergency room settings. The second part of the report dealt with behavioral interventions, prevention, and management of blood diseases. There is very little descriptive research published on the role of the family in the early life of individuals with chronic blood disorders. In addition, more work needs to be done concerning interventions for individuals who are having trouble coping with their disease. Those individuals who are depressed, and unable to function in work environments need special attention. Other areas for research include the role of psychosocial factors in pain management, and the role of interventions in improving quality of life issues. Finally, it was suggested that more individuals need to be trained in psychosocial research for sickle cell disease patients. Transgenic Animal Models for Sickle Cell Disease - Bold MRI - Dr. Mary Fabry, Albert Einstein School of Medicine Bold MRI stands for blood oxygen level dependent magnetic resonance imaging. This new imaging technique was first developed to observe areas of the brain during various activities and allows variations in metabolic rate to be quantitated. Bold MRI can detect high levels of deoxyhemoglobin, and therefore holds great promise as the first objective measurement of variations in body perfusion and oxygenation variations due to vaso-occlusion. Extensive Bold MRI studies are just beginning in the transgenic mouse animal model of sickle cell disease. Slides were presented demonstrating variations in signal activity over various organs before and after the mice were exposed to room air and then 100% oxygen. Human studies are just getting under way and hold the promise of allowing objective measurements of decreased perfusion during painful crises, and for diagnostic evaluation of avascular necrosis of bones. VII. UPDATE ON CORN ACTIVITIES Ms. Sonya Ross presented an update on activities of CORN. Currently, guidelines are under development for newborn hemoglobinopathy screening programs. There has been some concern about the content of the recommendations, and how they are to be used. The Sickle Cell Disease Advisory Committee was asked to provide two volunteers who would be willing to work with the newborn screening subcommittee of CORN to revise the newborn screening guidelines document. Drs. Buchanan, Davis, DeSimone, and Mentzer volunteered to look at the document before the next meeting of this committee. VIII. AGENCY REPORTS Health Resources and Services Administration (HRSA) Dr. Michelle Puryear, Chief of the Genetics Services Branch in the Office of Maternal and Child Health, reported on the addition of the National Hemophilia Program (Hemophilia Treatment Centers) to the Genetics Services Branch. This means that the most frequently diagnosed genetic hematologic disorders will come under the purview of her Branch (sickle cell disease, thalassemia, and hemophilia). The Genetics Services Branch recently supported the First National Genetics in Public Health Conference. In conjunction with the Agency for Health Care Policy, a cooperative agreement has been established to investigate health outcomes in children with genetic disorders and the relationship to specific structures within managed care. Department of Veterans Affairs (VA) Dr. Martin Steinberg reported that there has been an effort to increase research funding in the area of red blood cell disorders, and to attempt to attract young investigators to this field. The VA has a good track record for funding a large percentage of grant applications. Department of Defense (DoD) No representative present. Centers for Disease Control and Prevention. No representative present. IX. PROGRAM ACTIVITIES Dr. Duane Bonds, Leader of the Sickle Cell Research Group, described the plans for the upcoming annual Sickle Cell Disease Clinical Research meetings, to be held August 24-28, 1998 at the Natcher Building on the main NIH campus. The RFA grantees meeting will be followed on successive days that week by the Managed Care Workshop, the meetings of the Steering Committees for the CSSCD, MSH Patients's Follow-up, and the STOP Trial. In addition, the Sickle Cell Center Directors will be holding their second meeting of this year to coordinate planning with the newly funded Statistical Support Center. The Pediatric Hydroxyurea Study Group and the Acute Chest Study Group will also be meeting during the week. A new clinical trial will be starting under the umbrella of the Sickle Cell Centers - the Hip Core Decompression Trial which will be headquartered at the Northern California Sickle Cell Center under the direction of Dr. Elliott Vichinsky. Dr. Bonds announced that the FDA approved hydroxyurea for on label use in sickle cell anemia. Bristol Meyers-Squibb plans to begin marketing a specially packaged formulation for sickle cell anemia patients this summer. It is important for obtaining third party insurance coverage for this therapy that sickle cell anemia be listed as an indication for use. The pediatric hydroxyurea safety and dosing study was completed in January, 1998. Dr. Bonds reported on the Stroke Prevention Trial (STOP) which was terminated early. The committee discussed the potential false TCD positives and correlations with abnormal MRIs, TCD training and standardization, and problems of iron overload. General interest was expressed in other clinical research related to preventing strokes with other agents, such as hydroxyurea. There was extensive discussion of a number of proposed clinical studies and the need to establish priorities. These included the new conjugate pneumococcal vaccine, preventing end organ damage with hydroxyurea in children and other questions related to transfusion therapy to prevent primary stroke, and parvovirus B19. The Sickle Cell Disease Working Group met in January, 1998 to review research proposals for basic and clinical projects and made recommendations that will be forwarded to Dr. Lenfant. Dr. Charles Peterson was introduced to the committee. He is the new Director of the Blood Diseases Program, and will be coordinating the Hemoglobinopathies Clinical Network. The meeting was adjourned at 3:30 pm. FUTURE MEETING DATES November 13, 1998