Senator INOUYE. Like most of my colleagues, I have long supported nonanimal testing alternatives for our research community. How are we advancing in the computer area as an alternative? Dr. STEPHENS. I think that is coming along slowly. Although I think it is widely agreed that computer methods have great promise in the toxicity area, specifically in the initial screening stages, to quickly give toxicologists a feel for how dangerous a substance might be, it may not be the definitive test, but it can quickly give you an idea on hundreds of tests.

Senator INOUYE. I have received several letters from those who are still supportive of the use of animals and noted that the Humane Society has as part of its activities the putting to death of animals. What is the difference between that and putting animals to death in other ways?

Dr. STEPHENS. Well, we do not have animals at any of our facilities. I am not sure what those writers were referring to. At local shelters, it is the case that many of those animals are euthanized for lack of homes and that is an unfortunate situation.

The difference between that and medical research, it seems to me that they are quite unrelated. We are not saying do not use animals in research. Our thrust in this activity and elsewhere is to see if we can somehow get away from using animals when it is scientifically feasible, and we are trying to push that route through scientific innovation.

STATEMENT OF MARTHA ARMSTRONG

Ms. ARMSTRONG. If I may, I would like to comment. The MSPCA does run shelters. We have eight shelters in Massachusetts. And like the Humane Society of the United States, our position on the use of animals in biomedical research is not toward a total ban for

the use of animals in biomedical research; it is toward the humane use of animals in biomedical research and looking for alternatives when alternatives are available.

We think that to some degree the biomedical research community and those of us that run shelters and have to destroy animals would love to find another way to do both. But in the interim, we want to ensure that both the euthanasia of animals in shelters as well as the use of animals in research is done humanely.

Senator INOUYE. I agree with you and I think most of my colleagues do likewise.

Would you like to identify yourself so the record will show?

Ms. ARMSTRONG. Certainly. It is Martha Armstrong with the Massachusetts SPCA.

Senator INOUYE. I thank you, both of you.

Ms. ARMSTRONG. Thank you.

Dr. STEPHENS. Thank you, Senator.

STATEMENT OF THEODORE STEINMAN, M.D., PRESIDENT-ELECT, RENAL PHYSICIANS ASSOCIATION

Senator INOUYE. Our next witness represents the Renal Physicians Association, Dr. Theodore Steinman.

Dr. Steinman, welcome, sir.

Dr. STEINMAN. Mr. Chairman, I am Dr. Theodore Steinman, an associate professor of medicine at Harvard Medical School, director of the dialysis unit at Beth Israel Hospital, and the president-elect of the Renal Physicians Association, which I am representing today.

The Renal Physicians Association supports the recommendation of the ad hoc group for medical research funding of $9.77 billion for the NIH. We recommend funding for the National Institute of Diabetes, Digestive, and Kidney Disease of at least $790 million, compared to the administration's proposed level of $659 million.

The Renal Physicians Association strongly endorses increased funding for programs conducted through NIDDK's Division of Kidney, Urologic, and Hematological Diseases. Specifically, the Renal Physicians Association sees as critical areas of inquiry:

First, hypertension in blacks, native Americans, native Hawaiians. The Renal Physicians Association was involved in planning an initiative with NIDDK in developing a national cooperative study for this major public health problem because of the relatively high incidence of end stage kidney failure occurring in blacks and other individuals, as mentioned, as a result of hypertension, that was spoken about before.

The same is true for diabetes mellitus. Once the scarring process starts in both of these disorders, there appears to be no way to interrupt the progressive fibrosis. We need to study the biological response to cell injury and why progressive scarring occurs in response to these diseases.

Second, there is a need for research to improve methods for immunosuppression to prevent rejection in transplant patients While dialysis can control kidney failure, only successful transplantation can cure chronic kidney disease.

To give you an example, there is a novel new family of therapeutic compounds called fusion toxins, which are recombinant pro

teins assembled with genetic and protein engineering. These fusion toxins have been used experimentally in transplantation, recent onset diabetes mellitus, severe rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.

Preliminary clinical results have been extremely encouraging. For example, each of 10 patients with severe rheumatoid arthritis had dramatically improved symptoms following 1 to 5 days of treatment with the fusion toxin. In addition, a study in patients with insulin dependent diabetes mellitus has shown that there can be a dramatic reduction in the dose of insulin if the fusion toxin is given early.

This type of promising research has broad implications across many disease states and needs to be encouraged with more funding.

Third, research into the causes of morbidity and mortality in the dialysis patient population, and research in the technology of hemodialysis and peritoneal dialysis. The Renal Physicians Association is working with the NIDDK and other organizations in developing a 5-year scientific approach in this area.

Fourth, research on the biology of acute renal failure. Understanding the biology of acute kidney failure will help us design better treatment approaches with the potential for large cost savings.

PREPARED STATEMENT

Finally, the RPA strongly supports adequate funding levels for medical effectiveness and health services research conducted through the Agency for Health Care Policy and Research, including funding directed to support services on kidney disease outcome assessment, cost effectiveness, and clinical care decisions.

The Renal Physicians Association appreciate the opportunity to share its views with the committee. Thank you very much, sir. [The statement follows:]

STATEMENT OF DR. THEODORE I. STEINMAN

The Renal Physicians Association (RPA) is a professional organization of nephrologists whose goals are to insure optimal care under the highest standards of medical practice for patients with renal disease and related disorders, to act as a national representative for physicians engaged in the study and management of patients with renal disease and related disorders, and to serve as a major resource for the development of national health policy concerning renal disease. We are pleased to have the opportunity to provide the subcommittee with our testimony concerning fiscal year 1992 appropriations for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) within the National Institutes of Health, and for the Agency for Health Care Policy and Research (AHCP&R).

The RPA joins with numerous other professional and voluntary health organizations in support of funding for the NIH of $9.77 billion for fiscal year 1992. This recommended level, which is $995 million over the Administration's proposed budget, would provide the needed increase to sustain the growth of our nation's biomedical research enterprise, adequately train our next generation of scientists, and facilitate transfer of research advances to patient care and management applications. For the NIDDK, the RPA advocates funding of at least $790 million for fiscal year 92, compared to the Administration's proposed budget of $659 million.

Within the NIDDK, the proposed budget for the Division of Kidney, Urologic, and Hematologic Diseases represents a 7.1% increase over the fiscal year 1991 level, compared to an average increase among institutes NIH-wide of about 6%. The RPA agrees with the priority which is being placed on research within the mandate of the division. However, much more remains to be done. Last fall, the Department of Health and Human Services issued an NIDDK report on 'Efforts to Combat Kidney Disease in the United States. This report documented the scope and impact of kidney disease in this country and identified research accomplishments as well as planned areas of inquiry for the future. The RPA believes that this report will serve us well as we guide direction of future research funding decisions.

Collectively, kidney diseases represent one of our nation's most acute and growing public health problems. Direct costs associated with kidney diseases are estimated at more than $50 billion for 1990. Most importantly, the number of people who completely lose kidney function has risen at an annual rate of nearly 10% for the last decade, and continues to rise at about the same rate. Over the last few years we have achieved a significant increase in knowledge of kidney function and diseases. The field is now at the point where the application of advances in biomedical research can be expected to provide even more important information relevant to many types of kidney diseases, including congenital kidney diseases, and kidney disease associated with diabetes. RPA strongly supports the NIDDK's planned areas of emphasis in the area of biomedical research on kidney disease for fiscal year 1992.

We agree with other leaders in the kidney and urology community that appropriate components of Our recommendation for fiscal year 1992 NIDDK funding would include increased support for training, increased emphasis on individual research grants in kidney disease, and expanded funding for the clinical trial component of the institute's budget. However, one area in which research has been woefully lacking and for which we would like to provide specific justification, is research Into the causes of morbidity and mortality In dialysis patients and the diseases of other organs and organ-systems that occur in the dialysis patient, as well as research related to the technology of hemo- and peritoneal dialysis. It is essential that we undertake efforts to understand the causes of the excess morbidity and mortality in our dialysis population, compared to that found in many other countries. RPA is the only organization of nephrologists whose primary orientation is focused on all issues impacting the optimal delivery of health care to patients with kidney disease, especially quality issues and the issues surrounding health care financing. For this reason, we have worked with the NIDDK and others to plan for a research initiative to study a variety of influences on morbidity and mortality of chronic renal failure, (for example cardiovascular influences, infection and immunity problems, hormonal and metabolic influences, and nutritional factors). We hope that the Committee will take a strong interest in supporting this planned research initiative, especially in light of the potential we have to improve the rehabilitation of dialysis patients, and ultimately decrease the substantial costs of hospitalization that are currently associated with our large dialysis population. Any impact of science in decreasing morbidity would be of substantial benefit in light of increasing outlays which are now seen in association with inpatient services. For fiscal year 1992, we urge that funding directed toward basic and clinical research aspects of dialysis morbidity and mortality be provided to NIDDK, including support for a contract program focused on development of technologies.

Hypertension and diabetes mellitus are the two most common causes of chronic kidney failure, affecting blacks to a greater degree than whites. There is need to study the biological response to cell injury. It is unknown why there is a progressive scarring process in response to these diseases. Once the scarring process starts there appears to be no way to interrupt the progressive fibrosis. Also, there is a need to study the biology of acute renal failure. This problem is frequently a complication of underlying medical disorders. Knowledge about acute renal failure has laid dormant for almost thirty years. Acute kidney failure complicating another underlying illness leads to a great increase in the expense of hospitalization. Understanding the biology of acute kidney failure will help us design better treatment approaches, with a potential for large cost savings in patients with prolonged illnesses.

The NIDDK also shares responsibility with the Health Care Financing Administration for the U.S. Renal Disease Data Registry (USRDS). Because of RPA's emphasis on the cost and quality equation, we have taken a leadership role in efforts to shape the establishment and functioning of the USRDS. The legislative language which mandated the USRDS in the Omnibus Budget Reconciliation Act of 1986 specifies that the USRDS shall be established in a manner which will permit us to obtain the following information: "the economic impact, cost-effectiveness and medical efficacy of alternative modalities of treatment [section 9335i(B]); evaluation of the costappropriate allocation of resources for treatment and research into the cause of end stage renal disease [section 93351(C)] and mortality and morbidity rates and trends including other indices of quality of care (section 9335i(D)]. As the registry is currently operating, these requirements have not been met.

We urge the Appropriations committees to take specific steps to see that the scope of the USRDS is expanded to meet the requirements of the statutory mandate, and that the functioning of the system is integrated so that the activities conducted under HCFA and the activities conducted through the NIDDK can be coordinated and on-going, rather than conducted in a "piece-meal" fashion, as is currently proposed. Only with a completely integrated approach to quality assessment and cost issues can we expect to gain the answers that the Congress anticipated in establishing the system over 4 years ago. We are concerned that to allow the Registry to function without proper integration and coordination could ultimately deprive Congress and other health policy-makers of information they need to make informed decisions relating to the end-stage renal disease program.

Finally, and again based on RPA's primary orientation on issues related to the delivery and financing of care to the end-stage renal disease population, we would like to voice our continued support for the socio-economic research conducted by the Agency for Health Care Policy and Research (AHCP&R). RPA has long been a strong advocate for increased federal attention to, and support for, research focusing on the organization and delivery of medial care. We supported the creation of the AHCP&R, and especially the creation of the medical effectiveness research program. This program is aimed at developing scientific knowledge concerning patient outcomes through the development outcomes research methodologies; supporting and conducting outcomes research; disseminating information on quality and outcomes; and focusing on issues surrounding the creation and up-dating of clinical guidelines, standards, performance measures, and review criteria.

RPA is directly involved in the development of practice guidelines relating to kidney disease. Given the costs associated with providing care to the end-stage renal disease population, and the financial concerns inherent in the federal ESRD program, we believe that support for renal disease-oriented studies should be a high priority for the Agency. We urge the Committee to provide increased funding for the AHCP&R's medical effectiveness program directed to support of studies on kidney disease outcomes assessment and clinical care decisions.

Also within the purview of the Agency is research on general health services research, health care technology assessment, and health promotion and disease prevention activities. We believe that a research initiative on organ donation should be instituted as a part of this program. Although the replacement of a poorly-functioning kidney with a new, normal organ is an optimal treatment strategy, too few organs are now available, and only a small percentage of eligible patients receive a transplant. We believe that the Agency should be encouraged to conduct health services research specifically focused on procurement and transplantation practices in the immediate future.

The RPA appreciates the opportunity to share its views concerning fiscal year 1992 federal funding for key discretionary health programs with the Committee.