By Barry S. Coller, MD
2009-03-01
Dr. Coller is David Rockefeller Professor of Medicine, The
Rockefeller University. Dr. Coller is also Principal Investigator,
Rockefeller University Clinical and Translational Science Award.
The Clinical and Translational Science Award (CTSA) program is the
centerpiece of NIH’s Roadmap initiative to “reengineer the clinical
research enterprise.” The product of the recommendations of multiple
advisory committees under Dr. Zerhouni’s leadership, it was designed to
address the limitations of the General Clinical Research Centers (GCRC)
program, which it succeeded. Twelve CTSAs were awarded in 2006, 12 in
2007, and 14 in 2008, bringing the current total to 38. Ultimately, the
program is expected to have 60 centers.
The CTSA program provides significant resources that can be used to
advance the discipline of hematology. Below are descriptions of some of
those resources and a primer on how they can be harnessed to meet the
goals of the hematology programs at both CTSA and non-CTSA
institutions. CTSAs vary enormously in their orientations and programs;
some focus on the interface between basic research and human
early-phase investigation (“T1”), whereas others focus on the
dissemination of medical knowledge into the community (“T2”). Since it
is not possible to describe the full range of programs across all of
the CTSAs, I will primarily use the programs at The Rockefeller University CTSA, which I lead.
1. Training
A central element of the CTSA program is one or more K12/KL2 training
programs in clinical and translational research leading to either a
Master’s or PhD degree. At Rockefeller, for example, there is a
three-year Masters degree program (Clinical Scholars program) with the
potential for extension to a PhD degree. The program is similar to the
ASH Clinical Research Training Institute in goals, but with more depth
and breadth. The primary component is the design and execution of a
research project involving human subjects under the supervision of an
outstanding clinical or basic scientist. This is complemented by a
weekly tutorial that I lead on the elements of clinical and
translational science (including topics on protection of human
subjects, trial design, technology transfer, FDA regulations, and
conflict of interest). Another focuses on biostatistics and clinical
trial design. Other courses are available from among those offered in
the Rockefeller graduate school, including one on the application of
basic science techniques to human subjects research. Each scholar has a
three-person thesis committee that meets regularly to review progress.
Most of the scholars join the program after completing their
fellowships in subspecialties. The stipends are competitive and
scholars are eligible to apply for the NIH loan repayment program.
Thus, hematology fellowship program directors may benefit from working
closely with directors of K12/KL2 programs at their own or other
institutions to identify outstanding hematology trainees who may be
appropriate to join the program and be supported by the CTSA program to
conduct projects under a hematology mentor.
2. Pilot projects and innovative core facilities
Each CTSA has funds to support pilot projects in clinical and
translational science. This is an excellent source of start-up funds to
initiate new hematology research projects. The separate innovative core
facilities program provides additional opportunities for hematologists,
namely, the potential to both obtain funding to support the creation of
an innovative core related to hematologic disease and to use the
resources of all of the innovative cores that are developed and
supported by the CTSA for hematology research.
3. Access to a sophisticated infrastructure to conduct clinical studies
As the successor to the GCRC program, many CTSAs provide an extensive
infrastructure to facilitate human subjects protocol development and
implementation. A number of CTSAs have “navigation” or “concierge”
programs to help investigators navigate the complex regulatory
requirements to conduct their research. At Rockefeller, a clinical
research coordinator is assigned to each new clinical scholar to insure
that the research is conducted according to the high standard of Good
Clinical Practice (FDA guidelines). In addition, there are highly
trained research nurses and a hospitalist with extensive experience in
the design and execution of clinical studies. Finally, there are
experts in study monitoring and auditing. Similar infrastructural
elements are present in many other CTSAs.
4. Community engagement
All CTSAs have active programs to interact with their communities so as
to learn about the needs of community health-care providers and solicit
their ideas for additional research, as well as to facilitate
dissemination of knowledge into the community and insure that
individuals in the community have an opportunity to participate in
research conducted at CTSA institutions. Hematologists whose research
goals include clinical studies can both contribute to and build on this
infrastructure as they conduct their own studies.
5. National resources developed by the CTSA consortium
In addition to institution-specific programs, all CTSAs participate in
a national consortium committed to setting standards and providing
resources to all investigators. An extensive administrative structure
has been newly formed and committees are working on four major
priorities. A summary of the organization and goals of the consortium
is available on the Web site.
In addition, individual CTSAs are developing resources that are
designed to be made available to investigators nationwide and
worldwide. For example, at Rockefeller, the lead biostatistician has
extended methods based on U-statistics to structured multivariate data,
which are particularly valuable for integrating gene expression data
and clinical data. Software based on this methodology is being made
available to all investigators from CRAN,
and access to a grid of PCs, which provides the computational resources
to apply this methodology to genome-wide association and expression
studies, is available through the Rockefeller Web server.
As a result of my interest in hemostatic disorders, with CTSA
support, I have been developing an electronic bleeding history form for
research purposes. This is part of a larger human phenotyping
initiative that we are developing to complement the enormous amount of
genetic, proteomic, and gene expression data that are now becoming
available, so as to better understand the gene-gene, gene-environment,
and stochastic phenomena that affect the clinical expression of
disease. The goal of our project is to make this research tool
available to the entire academic community so that it can be used by
investigators anywhere in the world. We hope that this will make it
easier for junior physician scientist investigators to get started in
careers in hemostasis research. Moreover, if multiple investigators use
this same questionnaire, we hope to move to the next, and more
ambitious, phase of the project by encouraging investigators to upload
their de-identified data into a common database where the data can be
pooled. This has the potential to strengthen statistical power and thus
enhance the likelihood of successfully identifying the effects of
modifying genetic and environmental influences. We are also part of an
International Society on Thrombosis and Haemostasis group that is
developing a much shorter bleeding history questionnaire as a clinical
tool. We plan to also use our CTSA resources to convert that to an
electronic format and to host it on the Rockefeller University server.
When that questionnaire is complete, we will make it available to all
ASH members.
I hope this brief description of CTSA resources will encourage you
to make contact with CTSA leaders in your institution or, if you are
not in an institution with one, to search for CTSA-developed resources
available to non-CTSA investigators. Finally, CTSA leaders served as a
nucleus to create a new broad-based Society for Clinical and
Translational Science (SCTS) for all translational investigators. This
society is specifically designed to complement the role of ASH and
other subspecialty societies by focusing on the process of clinical and
translational research rather than the results of investigations in any
particular research area. SCTS will also focus on the interdisciplinary
teams needed to conduct clinical and translational research and the
need to partner with industry and governmental agencies. It will be
exciting to explore the many ways in which SCTS and ASH can work
together on common goals.
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