Richard Lottenberg, MD
2010-04-27
Professor of Medicine, Division of
Hematology/Oncology, University of Florida, Chair, ASH Government Affairs
Committee’s Sickle Cell Disease Subcommittee
Two years have passed
since the National Heart, Lung, and Blood Institute (NHLBI) announced the
restructuring of its sickle cell disease (SCD) research program, and despite
steps to strengthen the program and research in hemoglobinopathies, the SCD
community is still unclear about the Institute’s plans for creating a
sustainable program that encourages innovative and ongoing research. ASH has
received questions from members about NHLBI’s long-term plans for large-scale
clinical trials, basic and translational research, SCD scholar and trainee
programs, and support for health services research. In response to these
concerns, ASH met with NHLBI leadership to clarify the Institute’s plans for
moving forward. ASH will continue to work with NHLBI as the Institute
restructures its hemoglobinopathy portfolio to ensure that the program
encourages and supports important research. The Society will continue to keep
members apprised. The following is an update provided by Dr. Keith Hoots,
director of NHLBI’s Division of Blood Diseases and Resources (DBDR), summarizing
the Institute’s current and future hemoglobinapothy research program.
NHLBI New R34
Hemoglobinopathy Initiative and Restructured Sickle Cell Disease Research Program
The DBDR continues to adjust its
programs to ensure their alignment with the research goals outlined in the
Institute’s Strategic Plan (www.nhlbi.nih.gov/about/strategicplan/). The
Institute is focused on the scientific opportunities, informed by the public
health needs. Two key principles in program development are working in
partnership with multiple constituencies and ensuring that the mechanisms of
grant or contract support (investigator-initiated research, organized programs,
or a combination of these) are appropriate to achieve the goals. Decisions
about renewal of all programs at NHLBI are dependent upon an analysis of their
productivity and ongoing research needs, as well as emerging scientific
opportunities.
The DBDR recently created a new R34
planning grant for large clinical studies in hemoglobinopathies. The focus of
this initiative is to validate new and scientifically provocative hypotheses
for development into phase III clinical trials. During the one- to three-year
period the grant investigators will be funded (up to $250,000/year, maximum
$450,000 over 3 years) to do any or all of the following: design, establish
feasibility, determine sufficient statistical power, recruit trial sites,
establish an IRB plan, and/or even perform phase I or II pharmacokinetics on a
candidate IND drug for treating hemoglobinopathies. Up to six such planning
grants will be funded (likely in early 2011) to represent the vanguard of a
planned broad portfolio of funded phase III clinical trials in
hemoglobinopathies.
In addition, DBDR has a number of
completing, ongoing, or soon-to-be-enrolling clinical trials: SWiTCH (a
randomized study comparing hydroxyurea and phlebotomy to hypertransfusion in
patients with SCD and previous stroke), TWiTCH (a phase III non-inferiority
study that compares hypertransfusion to hydroxyurea in children with abnormal
transcranial Doppler studies to prevent stroke), Baby HUG (a pediatric phase
III clinical trial of hydroxyurea versus placebo), Walk PHaSST (a recently
completed double-blind randomized clinical trial of sildenafil vs. placebo to
enhance exercise capacity in patients with SCD and pulmonary artery
hypertension), and IMPROVE (a comparison of a high-demand/low-dose strategy of
opiate therapy vs. low-demand/high-dose opiate administration in SCD patients
with pain secondary to vaso-occlusive crisis). NHLBI also funds bone marrow
transplantation trials for patients with SCD and thalessemia through the Blood
or Marrow Transplantation Clinical Trials Network.
Several active research initiatives
have been developed to supplement the capacity of hematologists to assess clinical
outcomes: The Sickle Cell Quality of Life Measurement Information System
(ASCQ-Me) is an effort to develop, validate, and disseminate a psychometrically
sound and clinically useful instrument to assess health-related quality of life
among adults with SCD. It is fully integrated into an NIH-wide Patient-Reported
Outcomes Measurement Information System (PROMIS).
NHLBI’s Basic and Translational
Research Program (BTRP) supports research in hemoglobinopathies. This is
designed to supplement the bedrock of all DBDR research support, which is
investigator-initiated research projects (R01s and program project grants) that
represent approximately 75 percent of all DBDR extramural funding. The BTRP
initiative supports 10 large grants that focus on such diverse objectives as
endothelial function in patients with SCD, gene therapy for SCD, red cell
membrane function in SCD, and innovative physiological measurements in SCD
patients. Each of these funded sites also has a hemoglobinopathy- focused
training component that supports career development of Sickle Cell Scholars.
Fundamentally, a national hemoglobinopathy
research program requires a focused collaboration with federal partners, such
as the Health Resources Service Administration (HRSA), which supports care, and
the Centers for Disease Control and Prevention (CDC), which directs the public
health role for hemoglobinopathies. Accordingly, the three federal partners are
working together with state health departments through the newly constituted
Registry and Surveillance Program in Hemoglobinopathies (RuSH) to expand public
health tracking of patients with hemoglobinopathies. Further, the three have
partnered to insure that expanded hemoglobinopathies-focused goals and
objectives have been included in Healthy People 2020 targets for the U.S.
Department of Health and Human Services.
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