Title: Workshop on Sickle Cell Disease Cochairs: George R' Buchanan, MD and Marilyn J' Telen, MD Objective:
1Workshop on Sickle Cell DiseaseCo-chairs
George R. Buchanan, MD and Marilyn J. Telen, MD
Objective To construct a research agenda
aimed at better defining risk factors which
predict later adverse outcomes in sickle cell
disease, with particular emphasis on end organ
failure in adults.May 8-9, 2007Washington,
DC
2About ASH
- ASH is the worlds largest professional society
(over 15,000 members worldwide) concerned with
the causes and treatment of blood disorders.
Members include clinicians, researchers,
academicians, and students of hematology. - ASHs Mission To further the understanding,
diagnosis, treatment, and prevention of disorders
affecting the blood, bone marrow, and the
immunologic, hemostatic and vascular systems, by
promoting research, clinical care, education,
training, and advocacy in hematology.
3Background to ASH Participation in the Sickle
Cell Summit
- 2005 ASPHO invited ASH to participate in a
Sickle Cell Disease Summit. - December 2006 ASH chose to concentrate on the
area of research. - February 2007 Drs. George Buchanan and Marilyn
Telen were asked to chair a workshop on setting a
research agenda for sickle cell disease
4Workshop FocusMethods to Predict Risk of Later
Complications at an Early Age
- Life expectancy of patients with SCD continues to
increase. - As patients live longer, they develop more
end-organ damage as a consequence of SCD. - There is a large degree of variability among
patients regarding the complications of SCD they
experience. - We need to understand risk in order to test
preventive as well as treatment approaches.
5Workshop Hypotheses
- Advances in the prevention and treatment of
sequelae of SCD will require understanding the
processes that produce early and often undetected
end-organ damage during childhood. - Clinical studies of diagnostic tools, as well as
preventive and treatment strategies, will have to
span the pediatric-adult divide in order to
succeed in improving organ function. Improved
knowledge of the natural history of organ
pathology over time is also needed.
6Methodology
- Goal To promote stimulating, focused and
well-informed discussion of key topics and
research questions. - Strategy
- Discussion leaders and discussants were
identified for a number of key topics/organ
systems. - Topics and talking points were established and
distributed prior to the workshop, through small
group teleconferences. - Reference lists were also distributed.
7Discussion Topics
- Target organs known to be affected by SCD, as
well as pain. - Traditional and new methods for monitoring organ
function and predicting risks of complications - Currently available preventive therapies.
- What is in the pipeline.
8Outcomes of the Workshop
- Overwhelming support for a larger and more
inclusive multi-institutional collaborative
clinical research group, modeled after the
cooperative oncology trials groups. - A detailed report with prioritized research areas
will be presented to the ASH Executive Committee
by September and then forwarded to interested
agencies, including NHLBI, NIDDK, CDC, as well as
published. - It is hoped that this effort will also lead to
one or more RFAs from NIH.
9ASH Research Agenda
- Establishment of a Sickle Cell Disease
Collaborative Research Group - Infrastructure and operation How will it work?
- Mission What should it do?
- Vision What elements are necessary for its
success?
10ASH Research Agenda
Sickle Cell Disease Collaborative Research
Group (The Group)
- New organization needed to spearhead research
agenda - Focus on prevention of organ damage in adults
- Supplement existing NIH-funded clinical research
initiatives - Modeled after NCI cooperative trials groups
and/or comprehensive hemophilia center network
(MCHB/CDC) - Inter-agency partnerships and other linkages
required
11ASH Research Agenda
Infrastructure and Operation of The Group
- Necessary Components
- National database/registry of patients with SCD
- Inclusive
- Representative
- Secure
- Nimble
- Laboratory bank or repository linked to registry
for biomarkers and genomic studies - Availability of database and specimens for
translational research - Highly skilled research staff (faculty, nurses,
data coordinators) at Group sites - Robust training environment
- Novel peer-reviewed funding mechanisms
12ASH Research Agenda
Sickle Cell Disease Collaborative Research
Group (The Group)
- The Mission What are the Groups Aims?
- Establish valid and reliable definitions of
disease severity (overall and organ-specific) - Characterize disease phenotypes (e.g.,
vaso-occlusive and hemolytic) and their
pathophysiology - Develop better means of measuring early organ
damage and foster conduct of organ-specific
intervention trials (Example pulmonary
hypertension)
13ASH Research Agenda
Sickle Cell Disease Collaborative Research
Group (The Group)
- Execute large scale trials of hydroxyurea and
chronic transfusion, including careful study of
effectiveness as well as efficacy - Better characterize clinically relevant
endpoints, including mortality, event rates,
hematologic measures, and HRQOL - Understand sickle cell pain, collaborating with
pain experts in other disciplines - Design small molecules that inhibit sickling
- Expand stem cell transplantation opportunities
- Collaborate far more with the international SCD
community
14ASH Research Agenda
Sickle Cell Disease Collaborative Research
Group (The Group)
- The Vision What Elements are Necessary for The
Groups Success? - Collaborative spirit among investigators and
institutions - Training of more clinical and translational
investigators - Increased funding from NIH starting with RFAs
for pilot projects - Involvement of HRSA, CDC, CMS in supporting the
research agenda - Active engagement of relevant advocacy groups,
community organizations, and professional
societies - Recognizing and overcoming barriers to success