Hematology Research at the NIDDK
Griffin Rodgers, MD
Dr. Rodgers is Director of the National Institute of Diabetes and Digestive and Kidney Diseases.
As the newly appointed Director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), I want to underscore the Institute’s commitment to vigorous, multi-pronged research efforts to combat the diseases within our research mission. I am pleased to have the opportunity to share with the hematology research community my vision for the Institute over the next few years, with specific examples related to research in the field of hematology.
Within the National Institutes of Health (NIH), the bulk of hematology research is supported by the NIDDK, the National Heart, Lung, and Blood Institute, and the National Cancer Institute (NCI). The NIDDK is home to the oldest hematology research program at the NIH and supports basic science and translational research studies in this discipline. The Institute’s multi-faceted hematology research program focuses on understanding basic cellular and molecular mechanisms that underlie the production and function of blood cells in health and disease. Major areas of interest include diseases such as sickle cell anemia, thalassemias (for example, Cooley’s anemia), disorders of blood cell production (such as aplastic anemia and rare inherited bone-marrow-failure syndromes), iron-deficiency anemia, hemolytic anemias, and the so-called anemia of inflammation and chronic disease (AI/ACD). Moving forward, we will continue to pursue the most compelling research to address these and other debilitating and costly chronic diseases. Moreover, we will remain firmly committed to basic and translational hematology research, research training and career development, and the dissemination of health information to improve the lives of patients, their families, and those at risk for these diseases.
Working with the investigative and lay communities, we at the NIDDK will build upon emerging opportunities that are the fruits of past research investments. Through careful planning and analysis, we will meet the challenge of deploying our budgetary resources in the most effective ways to sustain research momentum and capitalize on research achievements. In moving research forward, the following overarching principles will guide my leadership as the new Director of the NIDDK:
Maintain a Vigorous Investigator-Initiated Research Portfolio. Innovation and problem-solving of individual investigators are crucial for research progress. Therefore, the NIDDK will maintain funding of investigator-initiated grants at the highest possible level. The Institute supports a broad portfolio of investigator-initiated research in the area of hematology, including studies of iron metabolism, the regulation of hemoglobin expression by red blood cell precursors, hematopoietic stem cell biology, and congenital and acquired anemias, including sickle cell disease, thalassemias, and AI/ACD.
We will also maximize our investments by supporting cross-cutting science that is broadly applicable to many disease-specific research issues. Examples of this research include identification of biomarkers and enabling technologies that can aid in the diagnosis of disease and in the assessment of new treatments in clinical trials. We will also continue to invest in the development of cell-based therapeutic approaches for repairing damaged tissues. For example, insights gained from NIDDK-sponsored research on the regulation of fetal and adult globin gene expression in red blood cell precursors have provided a basis for the development of molecularly targeted agents. Successful development of such gene-targeting agents offers great promise for effective treatment of genetic diseases of hemoglobin, such as thalassemia and sickle cell disease. We will also continue to use cutting-edge research methods, such as high throughput analysis, for identification of new candidate drugs. We are also supporting research on gene-environment interactions and other cross-cutting areas that have broad application to a wide range of diseases.
Support Pivotal Clinical Studies and Trials. The NIDDK’s hematology research program focuses primarily on basic research, but many studies supported by the Institute have the potential to improve patient care and are translational in nature. For example, we have long supported basic studies of iron absorption, transport, and storage. Studies supported by the NIDDK have led to a better understanding of how different iron-chelating drugs remove iron from body tissues in patients with iron overload disorders. This knowledge has, in turn, led investigators to investigate "smart" combinations of chelators that may enhance the effectiveness of iron removal, while decreasing the doses of drugs needed for effective treatment. Also, non-invasive imaging approaches to measure iron stores in the body — primarily in the liver and heart — can contribute greatly to the effective clinical management of patients with diseases of iron overload. Therefore, we are supporting studies of magnetic resonance imaging (MRI) as a potentially useful and widely available technique for monitoring excess iron in the body.
As a hematologist who has conducted research in the NIDDK intramural program for many years, I am proud of our vigorous studies. Our researchers are seeking to understand the molecular mechanisms responsible for diseases involving erythroid cells and the interactions between nitric oxide and hemoglobin. We are also studying ways to use bone marrow transplants or hematopoietic stem cells to treat thalassemias and other hemoglobinopathies. My own efforts have focused on basic and clinical research in hemoglobinopathies and other genetic blood disorders. These studies contributed to the development of the first FDA-approved drug to treat sickle cell anemia.
Many hematologic disorders, such as sickle cell anemia, disproportionately affect minority populations, and we will continue to search for insights and answers to these health disparities. We are also maximizing our investments by expanding the investigative community’s access to very valuable research resources accrued in our major clinical trials. To this end, we are funding ancillary studies to these trials and supporting a central repository for biologic materials from clinical trials.
Preserve a Stable Pool of Talented New Investigators. The ideas and fresh perspectives of new investigators invigorate the research community. Thus, we will work to ensure that new investigators realize their potential for contributing to biomedical research, and that today’s generation of young scientists will view research as a viable career. Our efforts will include fostering mentorship of new investigators and promoting special consideration for funding of talented new investigators.
The NIDDK has created a number of special opportunities for new investigators. For example, over the past several years, applications for regular research grants (R01 grants) from new investigators received a two-percentile-point advantage in funding consideration compared with applications from established investigators. More recently, new investigator applications that have just missed our general funding line — commonly called the payline — have received individual consideration for possible award through an approach we term "special emphasis funding." NIDDK Program Directors also give new investigator applications special consideration for short-term support (R56 awards) to help explore a research concept that was proposed in an initial application that scored outside the payline. This type of award helps investigators collect preliminary data in order to submit a revised, stronger application for a longer-term regular research grant.
The NIDDK also has a vigorous research career-development award program for scientists who are at early stages of their careers. These opportunities will be complemented by NIDDK’s participation in NIH-wide efforts that support new investigators, such as through the NIH Pathway to Independence Program and the NIH Loan Repayment Program. The NIDDK’s Division of Kidney, Urologic, and Hematologic Diseases regularly co-sponsors workshops for new investigators who are given career-development awards. At these workshops, members of the staff meet with attendees and discuss the workings of the NIH, and senior investigators from the hematology community provide grant-writing suggestions and career advice.
Foster Exceptional Research Training and Mentoring Opportunities. Maintaining an NIDDK-focused pipeline of outstanding investigators is critically important to our research progress against disease. We offer programs for individuals who are at different stages in their careers — ranging from those who have already attained advanced degrees to those who are very early in their educational development.
The National Research Service Award program of individual and institutional awards plays a critical role in fostering exposure to research environments and a commitment to a research career among individuals with doctoral degrees, medical degrees, or both. It also provides support for predoctoral fellows on institutional awards and for individual predoctoral students through the diversity fellowship program.
As a disease-focused Institute, the NIDDK needs to ensure a cadre of well-trained, subspecialty physician scientists. Special encouragement is given to individuals with medical degrees, and to medical students, to consider an academic research career. For example, the NIDDK provides short-term summer research training experiences through NIDDK-supported institutional awards. Another avenue is a program that provides support for a few medical students to take a one-year leave of absence from their studies to pursue a more in-depth research-training experience.
Promising postdoctoral fellows and junior faculty are encouraged to apply for one of the career-development awards supported by NIDDK, including mentored awards for physician scientists, research scientists, patient-oriented researchers, and individuals wishing to pursue a career in quantitative research. Mid-career, patient-oriented investigators are encouraged to continue their mentoring activities and focus on their clinical research.
In addition, we encourage minority investigators to apply for all of our research-training and career-development awards and support a Network of Minority Research Investigators to further their long-term academic research careers.
Ensure Knowledge Dissemination Through Outreach and Communications. We are continuing efforts to ensure that the science-based knowledge gained from NIDDK-funded research is imparted to health-care providers and the public for the direct benefit of patients and their families. For example, the NIDDK’s Hematologic Diseases Information Service provides publications about hematologic diseases to the public and to health fairs and community events.
Other NIDDK programs complement the Institute’s strong portfolio of basic research in hematology. For example, we launched a major research initiative in 2002 to identify the gene expression profiles of hematopoietic stem cells and related cells. Investigators in the Adult Hematopoietic Cell Lineage Genome Anatomy Projects were charged with developing protocols and reagents for characterizing cells in the hematopoietic stem cell lineage and their gene expression patterns using advanced technologies and bioinformatic techniques. The objective of the program was to create a nucleus for hematology research and promote the application of stem cell research to hematologic diseases and other health conditions.
Other examples are the Centers of Excellence in Molecular Hematology. The objective of these Core Centers is to bring together investigators from relevant disciplines to enhance and extend the effectiveness of research related to hematologic diseases and their complications. Clinical and basic science investigators are brought together in a manner that will enrich the effectiveness of hematologic diseases research. Each Core Center has a central focus of research investigation that is related to a hematologic research emphasis of the NIDDK.
Importantly, as we plan for the future, we will continue to seek and value external advice from investigators, professional scientific organizations, patient advocates, and the public. Key sources of input will continue to be our National Advisory Council, strategic planning processes, ad hoc planning groups, and scientific conferences and workshops. The Hematology Interagency Coordinating Committee provides a valuable forum to solicit stakeholder input regarding the setting of priorities and the planning of research goals. This input will provide a useful scientific guidepost as we make resource allocation decisions. Active collaboration with other components of the NIH and other federal agencies will also remain a cornerstone of NIDDK planning efforts. We will continue to seek and value such planning processes as we move forward.
Ever-increasing knowledge and the advent of new technologies bring new scientific opportunities for alleviating and conquering the many chronic diseases within the NIDDK’s mission. Our continuing goal will be to seize and maximize these opportunities to reduce the burden of disease and improve the public health. I look forward to working with the NIDDK’s many stakeholders in the hematology community now and in the future.
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News Headlines from Washington
CMS Finalizes National Coverage Policy for ESAs
The Centers for Medicare and Medicaid Services (CMS) finalized its national coverage
determination (NCD) for non-renal uses of ESAs on July 30.
The new policy does not include myelodysplastic syndromes (MDS), which means that ESA
treatment for Medicare beneficiaries with MDS is covered without any conditions or limitations.
Local Medicare carriers may continue to make local coverage decisions that are not included in
this national coverage decision. ASH will continue to monitor this situation and work with local
carriers as issues arise.
The NCD includes several limitations for patients undergoing ESA treatment for the anemia
secondary to myelosuppressive anticancer chemotherapy in solid tumors, multiple myeloma,
lymphoma, and lymphocytic leukemia. As this issue of The Hematologist went to press, ASH was
continuing to weigh in with CMS about concerns that the policy does not allow the hemoglobin
level to go above 10g/dL without stopping therapy. ASH has recommended a policy that allows a
target range between 10-12g/dL.
ASH was deeply concerned with CMS’s proposed coverage decision that was released in May
because the proposal was not supported by scientific data and was in conflict with expert
analysis. ASH submitted comments and met with CMS officials as well as testified before FDA’s
Oncology Drug Advisory Committee and met with FDA officials to discuss concerns and
recommendations. ASH and the American Society of Clinical Oncology (ASCO) are scheduled to
jointly publish an update of our guidelines on the appropriate use of Epo in September.
During the ASH annual meeting in December, the Practice Forum will address this issue. The
Practice Forum, "Evidence, Safety, and Clinical Decision Making: The Case of ESAs," is
scheduled for Saturday, December 8, at 6:00 p.m.
FY 2008 Budget Process: ASH Continues to Advocate for Larger Increase for NIH
As congressional leaders maintain their intention to adjourn for the year by late October,
Congress is continuing the process of drafting the bills that will fund federal departments,
agencies, and programs for fiscal year (FY) 2008.
Over the summer, the House and Senate Appropriations Committees proposed funding levels for
various federal programs and agencies, including the National Institutes of Health (NIH). The
House version of the FY 2008 Labor-HHS spending bill provides a net increase of $549 million
(1.9 percent) over FY 2007 for NIH. Meanwhile, the net increase proposed by the Senate for the
NIH budget in its draft bill is $799 million (2.8 percent) over FY 2007. As this issue of The
Hematologist went to press, President Bush indicated his intentions to veto the bill due to its cost,
and it appeared that full Senate passage may not come until October. Many in Washington are
expecting that agreement between the House and Senate is unlikely, which would necessitate an
omnibus spending bill.
It is important to note that both the Senate and the House proposed funding levels for NIH in FY
2008 essentially represent a cut in NIH funding, since the small increases they provided do not
keep pace with the projected 3.7 percent increase in biomedical inflation for 2008.
ASH will continue its advocacy efforts supporting increases for NIH on Capitol Hill throughout the
remainder of the FY 2008 budget debate. With a very tight year expected for the entire federal
budget and many domestic programs facing cuts or minimal increases, significant grassroots
support for NIH funding is critical to gain any further traction for increasing NIH funding in the
budget process.
President Vetoes Stem Cell Research Bill; Congressional Leaders Continue the Fight to
Expand Federally Funded Stem Cell Research
As expected, President Bush vetoed the Stem Cell Research Enhancement Act (S. 5) in late
June. While congressional leaders hope to attempt to override the President’s veto, it is unlikely
that the bill has the two-thirds majority support in either the Senate or the House necessary to
override the veto.
Additionally, in response to President Bush’s veto of the bill, Senate Labor-HHS Appropriations
Subcommittee Chairman Tom Harkin (D-IA) and Subcommittee Ranking Member Arlen Specter
(R-PA) have included a provision in the Senate version of the FY 2008 Labor-HHS Appropriations
bill that would essentially overturn the President’s recent decision and make more embryonic
stem cell lines available for federal funding. The language inserted by Senators Harkin and
Specter, the chief Senate sponsors of the Stem Cell Research Enhancement Act, would allow
federal research funding on stem cell lines derived prior to June 15, 2007; current Bush
Administration policy allows for federal funds to be used only for research on embryonic stem cell
lines derived prior to August 9, 2001.
Because similar language was not included in the House version of the FY 2008 Labor-HHS
Appropriations bill, it remains unclear as to whether the stem cell language will be included in a
final version of the bill that would be submitted to the President.
Medicare Agency Proposes Physician Fee Schedule for 2008; Physicians Face 9.9 Percent
Cut Unless Congress Acts
CMS published its Proposed 2008 Medicare Physician Fee Schedule Rule on July 12, and as
expected the Agency proposed reducing physician payments by 9.9 percent beginning January 1,
2008.
ASH has been working with Congress to avert these drastic cuts. For the past five years,
estimated cuts to the Medicare physician payment rate have been temporarily avoided through
legislation. Currently, congressional committees in the U.S. House of Representatives are
working on legislation to address Medicare physician payment. However, even with congressional
action, the best scenarios would be a .5 percent increase or a freeze in the 2007 conversion
factor in 2008.
ASH has developed a detailed summary of the rule, including information about proposals to
report anemia quality indicators, compendia for medically accepted indications for off-label drug
uses, the 2008 Physician Quality Reporting Initiative, payment for intravenous immune globulin
(IVIG), and Average Sales Price issues, etc. The final rule will be published around November 1 and will go into effect on or after January 1, 2008.
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Take Action
Congress is nearing the final stages of developing spending levels for the National Institutes of Health (NIH) for FY 2008 and ASH needs to help to ensure that NIH receives adequate funding. As this issue of The Hematologist went to press, the House and Senate Appropriations Committees had completed drafting the bills that will fund federal programs for FY 2008, but it was unclear when or if the House and Senate would consider a conference bill. ASH and the biomedical research community continue to advocate for an increase of 6.7 percent for FY 2008 over the final FY 2007 levels, despite proposed FY 2008 increases by the House and Senate Appropriations Committees that fall well short of that level. Federal funding for domestic discretionary programs is exceptionally tight. It is essential that members of the research community from across the nation contact their Senators and Members of Congress about the importance of providing adequate funding for NIH. The ASH Advocacy Center makes contacting Congress quick and easy. The advocacy center identifies the user’s Senators and Representatives by zip code and provides a sample letter that can be e-mailed to the proper offices.
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