The National Heart, Lung, and Blood Institute (NHLBI) announced today a comprehensive and innovative restructuring of its research program in sickle cell disease (SCD).SCD is a serious inherited blood disorder that most commonly affects people with origins in Africa, Latin America, the Middle East, or the Mediterranean.Since 1972, the NHLBI has developed and maintained a major research effort to improve the lives of individuals with SCD.The studies have led to a number of effective approaches for the management and treatment of the disease, and today's patients live longer and have a better quality of life than was the case in previous generations.However, there is no cure for SCD, and therapies that exist do not benefit all patients.
The recent issuance of the Institute's Strategic Plan (http://www.nhbli.nih.gov/about/documents/strategicplan) and the scheduled renewal of the Comprehensive Sickle Cell Centers (CSCC) program provided an opportune time to rigorously assess the NHLBI program in SCD.The National Heart, Lung, and Blood Advisory Council conducted an extensive review of the Institute's research and training portfolio in SCD, taking into account responses received to a public solicitation for input from patients and lay and professional constituencies about the top scientific and clinical priorities.A detailed report on the Council's findings and deliberations can be found at http://www.nhlbi.nih.gov/research/reports/2008-scd-program. Recommendations include the following.
- Basic science — Research should focus on disease mechanisms; new treatment approaches; genes and genetics; molecular biology and biomarkers; vascular biology; erythropoiesis and red blood cell biology; and animal models.Progress in this area will require stimulation of investigator-initiated research applications, with careful attention to appropriate peer review, and expanded involvement of scientists from areas other than hematology.
- Translational and clinical research — Emphasis should be placed on pain pathophysiology and management; fetal hemoglobin induction; trials of promising alternatives to hydroxyurea; approaches targeting disease pathophysiology; curative therapies; and prediction, prevention, and management of severe manifestations and end-organ damage.The NHLBI should provide research resources such as databases for genotype–phenotype data and repositories for biological samples, encourage resource-sharing among investigators, and assist investigators in bringing clinically relevant basic science discoveries to the point where they are ready for human trials.
- Participation in clinical research — The Institute should increase the pool of potential participants for interventional and observational studies and to provide opportunities for geographically broad participation by individuals and investigators in research.
- Translation and dissemination to the community — Timely and thorough application of research findings should be promoted through development of evidence-based practice guidelines and their widespread dissemination via educational programs for physicians, other health-care providers, and patients.
Based on the NHLBAC recommendations, the NHLBI is moving forward with the following innovations to its SCD portfolio.
- Support for basic research will be expanded through funding of investigator-initiated grant applications and through NHLBI-initiated RFAs (requests for applications) focused on the pathophysiology of SCD, the biology of pain in SCD, fetal hemoglobin switching, and genetic modifiers of disease expression and progression.
- The Institute will reconfigure the CSCC program into a Basic and Translational Research Program by funding meritorious projects submitted in response to the recent RFA (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-06-008.html).The program will emphasize fundamental investigations and their translation into initial studies in humans, as well as community translation to promote evidence-based clinical practice.SCD Scholars programs for the career development of young investigators and Summer-for-Sickle-Cell-Science programs for research training and mentoring of high-school students also will be supported as part of a larger effort by the Institute to prepare the next generation of scientists to advance the field of SCD research.
- The NHLBI has requested comments from its constituency regarding interest in joining the RAID (Rapid Access to Interventional Development) program of the National Cancer Institute, which provides contract services to aid in the translation to the clinic of potential new therapeutic agents originating in academia (http://grants.nih.gov/grants/guide/notice-files/NOT-HL-08-111.htm).The RAID offers an avenue for swift progress in evaluation of promising therapeutic approaches such as innovative drugs to stimulate fetal hemoglobin production.
- The NHLBI will develop a new Clinical Trials Research Network (CTRN) designed to open participation in clinical research to a much larger number of investigators and individuals with SCD than is currently possible.Structured similarly to the Children's Oncology Group (http://www.childrensoncologygroup.org/, which offers clinical trial participation to all eligible subjects and investigators, the CTRN will, in time, subsume the current SCD Clinical Research Network (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-05-006.html).
- The NHLBI will expand its support of genomic research in SCD beyond the boundaries of current efforts being conducted within the framework of the CSCCs (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-05-006.html) by developing a program like the Framingham SHARe (SNP Health Association Resource— http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000007.v2.p1) with contributions of genotypic and phenotypic data from many investigators and their patients and free access to qualified researchers.
- Finally, the Institute will undertake a focused effort to develop evidence-based guidelines for the care of individuals with SCD across the life-span that can be used by health-care practitioners throughout the world.An educational campaign will be launched, in partnership with the Sickle Cell Disease Association of America and other patient advocacy groups and professional organizations, to raise awareness about SCD and bring nationwide attention to its diagnosis and treatment.
By implementing these recommendations, the NHLBI intends to take advantage of existing scientific opportunities and make SCD resources more widely available, better serving both the SCD research and the patient communities.
Inquiries may be directed to:
Susan B. Shurin, M.D.
National Heart, Lung, and Blood Institute
Building 31, Room 5A48
9000 Rockville Pike
Bethesda, MD 20892- 2486
Telephone: (301) 496-1078
Fax: (301) 402-0818