Securing the Health Americans

Submitted to the House Commerce Subcommittee on Health and the Environment
September 13, 2000

The Administration is pleased to have the opportunity to provide testimony for the record of the hearing by the House Subcommittee on Health and the Environment concerning the following bills:

The Administration has not had the opportunity to review the House Resolution recognizing the importance of researching childhood cancers, and therefore, has no comment.

HR 2399 the National Commission for the New National Goal: The Advancement of the Global Health Act

In today=s world of increasing globalization, the United States continually faces new challenges and opportunities in public health. Transportation and population shifts make it possible for new and emerging diseases to travel swiftly across continents and around the world. In addition, disparities in health status have widened between developed and developing nations. In 1997, an Institute of Medicine (IOM) report concluded that active engagement in global health is a Avital interest@ of the United States, recommending that the country Aexert greater leadership in global health by taking full advantage of its strength in science and technology.@ The IOM determined that such action is necessary because of the need to protect the health of the US public, the anticipated benefits such engagement will yield for the US economy, and the importance of US leadership in science and technology. Facing these challenges requires even closer cooperation with our global partners in using science and sound policy to promote public health globally.

The Advancement of Global Health Act sets up a commission to recommend a strategy for the global eradication of disease and focuses primarily upon the global control of infectious diseases through the development of vaccines and the sharing of the health research information on the Internet. The bill would establish a structure duplicating the responsibilities of existing programs. There is already in existence the National Vaccine Advisory Committee (NVAC), which is a forum to address these issues. The purpose of NVAC is to advise and make recommendations to the Director of the National Vaccine Program (NVP) in the Office of the Assistant Secretary of Health on matters related to the vaccine program=s responsibilities. Staff support for NVAC is provided by the National Vaccine Program Office (NVPO) at the Centers for Disease Control and Prevention (CDC). The NVAC recommends ways to achieve optimal prevention of human infectious diseases through vaccine research and development, provides direction to achieve optimal prevention of adverse reactions to vaccines, and identifies areas of government and non-government cooperation to ensure the availability, distribution, and use of safe and effective vaccines. The ex-officio members of NVAC include representatives from the Department of Defense, the Food and Drug Administration, the Health Care Financing Administration, the Health Resources and Services Administration, the National Institutes of Health, and the HHS Office of General Counsel. In addition, the Director, National Immunization Program, CDC serves as a liaison representative on NVAC. It is unlikely that this new commission would bring added value to the effort to eradicate disease.

Other potential problems with the commission established by the bill are the lack of attention to the several critical issues to the eradication of diseases, including issues of vaccine availability and delivery, the role of non-vaccine interventions, and the opportunities for impacting non-infectious diseases such as those stemming from poor nutrition, vitamin deficiencies, and others.

Finally, if such a commission were established, it is not clear why the NVPO and the CDC are not mentioned in the membership of the proposed commission. NVPO is charged with coordinating vaccine policy and decision making across the federal government. CDC is the lead agency for disease eradication globally, including polio, guinea worm, lymphatic filariasis, and measles. CDC already plays a coordinating role for numerous vaccine related issues and has the necessary contacts and mechanisms in place with key international partners. If this commission is formed, CDC and NVPO should be included in the composition of the commission=s membership. The FDA, as the agency overseeing vaccine safety and the approval of new vaccines, should also have a role if this bill is enacted.

H.R. 762, the "Lupus Research and Care Amendments of 1999, " would require the NIH to expand and intensify research with respect to lupus; coordinate similar activities with other HHS components that have responsibilities related to lupus; and to conduct or support research to expand the understanding of the causes of, and to find a cure for, lupus. The bill would designate specific areas of research to be addressed such as determination of the reasons underlying elevated prevalence of lupus in women, especially African-American women; basic research concerning the etiology and causes of the disease; epidemiological studies on the natural history of the disease and population and ethnic differences; development of improved screening techniques; clinical research for the development and evaluation of new treatments; and information and education programs for health care professionals and the public. The bill would authorize $75 million for FY 2000, and "such sums as may be necessary for each of the fiscal years 2001 and 2002."

Systemic lupus erythematosus (SLE), or lupus is an autoimmune disease that can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels, and brain; it is a serious public health problem that mainly affects young women. The disease often starts between the ages of 15 and 44. Nine times more women than men have the disease. It is also three times more common in African-American women than in Caucasian women, and is more common in women of Hispanic, Asian, and Native American descent. African-American women tend to develop the disease at a younger age than Caucasian women and to develop more serious complications.

The primary reason for the optimism for the future of lupus patients comes from seminal studies from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Intramural Research Program that determined that treatment with immunosuppressive drugs (cyclophosphamide and prednisone) can prevent or delay kidney failure due to nephritis, one of the most serious common complication of this disease. NIAMS clinical investigators continue to study and refine treatment regimens for lupus nephritis.

A number of NIH institutes and offices support research and research training efforts related to lupus, and lupus is one of many diseases covered by the NIH Autoimmune Diseases Coordinating Committee. Although the cause of lupus is unknown, applied genetics have dramatically improved the pace of research by NIAMS-supported investigators for discovering the genes that contribute to lupus susceptibility, severity, and mortality. Using experimental animal models of lupus, investigators are uncovering the genetic factors involved. NIAMS-supported researchers identified, in mouse models of lupus, 7 to 10 gene regions that are linked to the disease. Some features of human lupus are readily apparent in these animal models. Recently, researchers have found an association between lupus and a region on chromosome 1. Fine mapping of this region has identified another candidate gene involved in immune function, specifically in the processes of DNA repair and cell death-both of which have been reported to be abnormal in lupus. The results to date suggest that lupus susceptibility genes are very similar in mice and humans, and that these same genes may be important in all racial groups. In addition, the identification of genetic risk factors in lupus could indicate which patients may potentially develop severe disease and therefore merit early, aggressive treatment. Recent studies yielded two such risk factors--absence of the C4a gene and changes in the Fc receptor gene. C4a and the Fc receptor are involved in the removal of proteins known as immune complexes, which, if not removed, stay in the body and cause tissue injury.

In other approaches to lupus, the NIAMS, the NIH Office of Research on Women's Health, and the NIH Office of Research on Minority Health are co-funding the first clinical trial on the safety of estrogens for women with lupus. At the present time, women with lupus are usually advised not to take any medications that contain estrogen in the belief that it will worsen their disease or cause problems with blood clotting. This leaves women limited options for contraception during child-bearing years and for hormone replacement therapy during postmenopausal years. These studies will focus on the effects of oral contraceptives on disease activity in women with lupus and on the effects of hormone replacement therapy with estrogen and cyclic low-dose progestins in postmenopausal women with lupus. Many of the patients recruited for this trial are minority women. The outcomes of this trial are expected to have a major impact on the treatment options, health, and quality of life for patients with lupus.

NIAMS is committed to enhancing basic, clinical, and translational research through a variety of mechanisms. Currently, the Institute is supporting two specialized centers of research in SLE. The first, at the University of Alabama in Birmingham, represents a unique consortium of research organizations and is studying the disease's genetic aspects. The second, at the University of Virginia in Charlottesville, is addressing genetic and immune mechanisms that underlie SLE flare-ups and organ damage. In addition, the Institute continues to fund the Lupus in Minorities (LUMINA) study, an effort designed to examine the relationship of socioeconomic, demographic, cultural, immunogenetic and clinical variables to presentation and early outcome in Hispanic, African American and Caucasian SLE patients.

NIAMS recently hosted two scientific workshops on SLE in collaboration with other NIH components; namely, the National Institute of Neurological Disorders and Stroke and the National Heart, Lung, and Blood Institute. The first meeting focused on central nervous system involvement in the disease and was designed to promote new scientific collaborations between neuroscientists and lupus researchers. The second workshop addressed heart disease and SLE, as premature cardiovascular disease in women with lupus has been underestimated in the past, although it is a major cause of morbidity and mortality. Both of these sessions identified gaps in SLE research and provided recommendations for future initiatives.

With respect to health education for patients with lupus and their care providers, the Institute is pleased to report that the recently published "Lupus: A Patient Care Guide for Nurses and Other Health Professionals" has been in steady demand. This resource guide represents a partnership between Federal health agencies and SLE voluntary organizations and provides a strong model for future information dissemination efforts.

NIH overall currently projects $52.4 million for research on lupus in FY2000, and estimates an increase to $55.2 million in FY2001 under the President=s budget. The bill would authorize a figure of $75 million for FY2000, a figure in excess of what has been estimated to be provided in the FY2000 budget. The NIH lupus efforts are already considerable and currently address the areas of research highlighted in the legislation. The NIAMS and other NIH components will continue to fund the necessary research to understand the causes and search for better treatments and screening methods within the context of the NIH budget.

Title II of this bill mandates grants for the establishment, operation, and coordination of effective and cost-efficient systems for the delivery of essential services to individuals with lupus and their families. It limits the charges imposed by grantees on services recipients; authorizes technical assistance, and includes an appropriation authorization level of $75 million.

The health centers eligible for these grants by law must offer a discounted fee schedule with only a nominal fee for patients at or below 100% federal poverty level, and a sliding scale for those between 100 and 200%. The fee structure already in place at health centers could be used for this program as well. While the bill addresses several services associated with the treatment of lupus, given the chronic nature of the disease, greater emphasis should be placed upon case management services, training of health center staff and other services to support the treatment of this condition.

Under the Federal Food, Drug, and Cosmetic (FDC) Act and related statutes, the Government has a vitally important role in helping to ensure that the medical products upon which patients and their health care practitioners rely are both safe and effective. These safeguards are particularly important for our most vulnerable citizens, those who are desperately ill. We believe the existing programs under which patients can obtain access to experimental therapies, and those under which we expedite approval of such therapies, establish the appropriate framework for achieving our mutual goal of providing patients with serious and life-threatening diseases the earliest reasonable access to promising therapies.

H.R. 3677, the AThomas Navarro FDA Patient Rights Act," amends the FD&C Act to restrict the authority of the Food and Drug Administration (FDA or Agency) to issue clinical holds regarding investigational drugs or to deny patients expanded access to such drugs under single patient INDs. FDA believes this bill would undermine FDA's ability to help assure reasonable safety and effectiveness of subjects in clinical trials and informed consent for patients given access to experimental therapies.

H.R. 3677 restricts FDA=s authority to place an Investigational New Drug application (IND) on clinical hold when there is a comparable or satisfactory alternative therapy. A clinical hold is designed to allow FDA to stop an investigator from administering an experimental therapy to patients where participation represents an unreasonable risk to potential patients. The reasonableness of the risk may depend on a number of factors including whether participation in the clinical trial would require the patient to forego a proven effective therapy.

Some of the additional reasons that a clinical trial may be placed on clinical hold include the following:

Unless a patient is aware of all the factors that may impact the risk/benefit analysis, a patient cannot be truly aware of the risk involved in receiving a particular investigational drug. Thus, requiring a simple declaration in writing that a person is aware of the risks may not provide acceptable patient protection and should not be substituted for the current human subject protections in place.

While this bill relies on patients waiving their rights to be protected from dangerous therapies, the bill does not preclude practitioners from either unknowingly or intentionally misleading patients with little or inadequate information and thus subjecting human patients to unorthodox testing of new medical treatments without adequate protections or information.

For a single-patient IND, we believe that the independent scientific consideration provided by the Agency is critical and is an essential component of patient protection, when one is considering drugs about which relatively little is often known. In the typical single patient IND situation, especially those involving emergency IND requests, the patient=s physician generally has only very limited information about the investigational therapy being requested.

The Agency=s primary responsibility in deciding whether to allow a single patient IND to proceed is to determine whether use of the therapy in the particular patient involved would be reasonable or safe. In oncology, for example, with respect to patients for whom no curative treatments exist, our practice has been to permit almost anything that is reasonably safe without regard to efficacy or potential efficacy. There may be several INDs for the same product with each sponsor working confidentially and in ignorance of what others are doing and of their results. FDA is often the only party that has all of the information and is therefore in a unique position to assess the results.

Indirectly harmful products are those that do not themselves cause injury, but may lead people to delay or reject proven remedies, possibly worsening their condition. For example, if cancer patients reject curative drug therapies in favor of unproven therapies and the unproven therapies turn out not to work, their disease may advance beyond the point where proven curative therapies can help. As long as a curative treatment for a disease is available, FDA cannot permit the use of an unproven product if such use requires that patients forgo proven treatments for one whose efficacy is unknown.

H.R. 1795, the National Institute of Biomedical Imaging and Engineering Establishment Act

The bill would create at NIH the National Institute of Biomedical Imaging and Engineering, a separate Institute at NIH for imaging and engineering, and would fund it for fiscal year (FY) 2000 by authorizing an amount for the new Institute equal to (plus inflation) what is currently spent by NIH Institutes for imaging and engineering programs. The bill would authorize the Director, NIH, to transfer appropriate personnel to the new entity. The authorization for FY 2000 would be Aequal to the amount obligated by NIH in FY 1999@ for biomedical imaging and engineering, adjusted for any necessary offsets occurring after October 1, 1998. For FYs 2001 and 2002, authorizations would be for the amount determined for FY 2000 adjusted for the fiscal year involved to offset inflation occurring after October 1, 1999. In establishing the Institute, the Director, NIH, would be authorized to transfer personnel, use appropriate facilities to house the new Institute, and obtain administrative support from other agencies of NIH. The Institute would be expected to have a 12-member advisory council, prepare a plan for submission to address the consolidation of the activities of the NIH biomedical imaging and engineering programs and the coordination of programs at NIH and with related activities of other Federal agencies.

The National Institutes of Health (NIH) invests significantly in research in bioimaging and bioengineering. In fiscal year 1997, NIH spent approximately $325 million in bioimaging research: $217 million was for basic research in bioimaging, and $108 million was for using imaging as a tool to conduct medical research. In fiscal year 1998, the bioimaging total had risen to approximately $339 million. There are comparable numbers for bioengineering. In fiscal year1997, NIH spent $413 million on bioengineering research and in fiscal year 1998, $501 million. (Bioimaging data for 1999 is still being compiled. Final totals will be available following review and concurrence by research institutes and centers.) There are overlaps between the bioimaging and bioengineering portfolio; and thus, approximately half of the bioengineering awards can be attributed to bioimaging research. These overlaps reflect the collaborative nature of bioimaging and bioengineering research, both are rooted in physics, mathematics, chemistry, biology, and the life sciences. NIH is making a large and growing investment in these fields and they are proving to be integral to the operations of all of the present Institutes and Centers.

Applying imaging techniques to scientific questions about health and disease is part of the basic mission of most of the institutes at the NIH. It is critical that the individual institutes and centers maintain their support for bioengineering projects that are informed by the compelling biological questions. For example, imaging plays a critical role in the objective evaluation of cognition in the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health (NIMH), and the National Institute on Aging (NIA) programs using functional MRI and PET imaging. Very active programs in data acquisition, image processing and evaluation are integral portions of these institutes and activities. In the cardiovascular area, cardiac magnetic resonance imaging (MRI) and ultrasound have recently improved in the National Heart, Lung and Blood Institute (NHLBI) by an intensive collaboration of physicists, cardiologists and engineers in government and industry, resulting in new commercial products that are currently being evaluated around the country. In all of these programs, the close collaboration between the engineers/physicists and the clinicians/biologists was critical for the rapid and effective development of the technology. The discovery of new imaging modalities and approaches is also fostered in this environment, since the engineers and physicists are constantly being challenged by their biology/clinician colleagues to develop new approaches to studying the body. A critical mass of engineers and physicists are present in many of these programs, providing the necessary technical and theoretical insight to develop these important steps in the biological sciences. There are many examples in the various institutes over the past several years in which significant discovery has occurred because of collaborations between physical scientists and biological scientists aimed at solving specific biological questions.

It is clear that as bioimaging is integral to so much of modern biology, the interest in imaging is found throughout the NIH, although historically the NCI has had the largest portfolio of bioimaging research. It is a challenge to separate the use of imaging as a tool from research on imaging because they are intertwined. The sense of where the science would benefit from new imaging tools leads the science. For example, to improve the diagnosis of a heart attack using MRI, chemists have played an important role in developing contrast agents to obtain a more vivid image of blood flow through the heart, while engineers have modified the MRI scanner to provide the necessary speed to freeze the motion of the heart, and computer scientists have provided the visualization tools to get the information to the clinician in a rapid and informative fashion. In this example, all of these allied scientists needed input and information from the biologists and clinicians on the nature of coronary blood flow in coronary artery disease on a day to day basis. Such cross-fertilization of scientific fields is fostered through collaborations within research groups with institutes and between different programs.

NIH has long recognized the importance of bioengineering and bioimaging. In February 1997 the Director established the Bioengineering Consortium at the NIH to bring all of the Institutes and Centers together to shape the future directions of the NIH in these areas and address problems raised by these scientific communities. This activity has been successful and NIH is now formalizing an Office in the Office of the Director to continue this work. In fact, this has proven to be such an effective mechanism, that in deliberating the strategies to support bioinformatics, it was recommended that a parallel activity be formed on that topic.

In regard to the Office, while it was originally established on April 5, 2000, the organization package was then revised on May 25, 2000 to incorporate bioinformatics. Hence, the Office of Bioengineering, Bioimaging, and Bioinformatices (OB3) was established. The date of initial operation of the OB3 depends on staff recruiting and hiring. A vacancy announcement for the Director position was released in mid-June and closed on September 7.

The mission of the OB³ is to provide a focus for biomedical engineering, bioimaging, and biomedical computing issues among the institutes and centers at the NIH and with other Federal agencies. The OB³ will conduct activities aimed at fostering new basic understandings and collaborations among the biological, medical, engineering, physical, and computational sciences. These activities include coordinating trans-NIH research programs, developing transdisciplinary training and career development opportunities between the technological and biomedical communities, and conducting symposia and technical meetings to facilitate communication and dissemination of information among different technical disciplines. The OB³ will not have nor seek to have grant-making authority or programmatic funds to support research. The Aoffice@ status will provide a dedicated infrastructure for coordinating bioengineering, imaging, and informatics issues and initiatives at the NIH while maintaining the trans-institute participation and communication that have been successful in the past. This is an efficient and effective strategy for enhancing the support for bioengineering, bioimaging, and bioinformatics while still retaining their close linkage with the individual research Institutes and Centers.

Biomedical engineering and imaging are multi-disciplinary fields that benefit all NIH research institutes and centers in their missions to improve the quality of the nation=s health. Bioengineering/bioimaging research is highly important to the NIH and to the future of biomedicine and is supported across all of the NIH ICs. Recognizing the trans-institute applicability and value of bioengineering (and bioimaging), the Bioengineering Consortium (BECON) was established in 1997 to provide a focus for bioengineering activities at the NIH, a mechanism for problem solving and a way to launch initiatives that were broader than one or two Institutes. The BECON consists of staff from all NIH research institutes and centers plus representatives of other Federal agencies concerned with biomedical research and development. Since its establishment, the BECON has coordinated research and training opportunities in biomedical engineering; sponsored major annual symposia aimed at fostering communication between the engineering/physical science and biomedical communities; and conducted monthly meetings open to the public to identify and discuss issues related to bioengineering including imaging, informatics, biomaterials, and bioprocesses. The research initiatives have been hugely successful resulting in far greater support for initiatives than originally envisioned. The symposia have brought in record audiences and service to provide direction to the Institutes and to the NIH as a whole.

In mid-2000, the BECON will transition into the OB3 within the Office of the Director. OB3 will then serve as a focus for bioengineering efforts at the NIH institutes and centers and provide a vehicle for enhanced interagency activities. This will also provide sufficient staffing to support additional activities with the NIH intramural program. Tthe OB3 will not have nor seek to have grant-making authority or programmatic funds to support research and will serve as a focus for bioengineering activities at the NIH. This "office" status will provide a dedicated infrastructure for coordinating bioengineering issues and initiatives at the NIH while maintaining the trans-institute participation and communication that has produced success in past endeavors. Moreover, as part of the Office of the Director, it will enhance the visibility of NIH=s programs and activities in bioengineering.

Bioengineering and bioimaging are a rapidly developing field with multi-institute applications. Establishment of a separate institute to coordinate communication, management, prioritization, and accountability is premature at this time. Furthermore, removing the bioengineering and bioimaging initiatives from the institutes in which they are currently located could have the unintended consequence of reducing the ability of Institutes and Centers, over the long term, to support the very research that this legislation is deigned to promote. Experience with the OB3 will contribute to the evaluation of the need for a separate institute for bioengineering and bioimaging at the NIH.