STATEMENT OF RALPH CAZZETTA

I am Ralph Cazzetta, a patient with Cooley's anemia, and President of the Thalassemia Action Group (TAG). With me are Sophie Shioshilos, also a patient, and Peter Chieco, the parent of a patient.

As you will recall, Cooley's anemia, also known as Thalassemia Major, is a catastrophic blood disease of genetic origin, recognized by the World Health Organization as the world's commonest lethal inherited disease, striking predominantly those of Italian, Greek (and other Mediterranean origins) and Asian, Arabic and other groups.

Patients require repeated blood transfusions to replace defective blood cells carrying abnormal hemoglobin, and those patients develop a lifethreatening iron overload as a result of the transfusions.

Iron overload can be managed with the iron chelating drug Desferal, but Desferal is very expensive and it must be administered via injections over a 12-hour period daily, and because of the inconvenience and difficulty, it has a dangerously high rate of non-compliance in teenage patients.

This problem of non-compliance is one of the reasons we created TAG (the Thalassemia Action Group), to provide peer support to our fellow patients to keep to the Desferal regimen, as difficult and painful as that may be. You will be interested to know that we began our efforts only 4 years ago, supported by leaders of the Cooley's Anemia Foundation, with some funding from the Maternal and Child Health Bureau, to pull together American patients.

Also, the Foundation has spearheaded the development of the Thalassemia International Federation (TIF). That organization, in the last 4 years has had 4 international meetings in 4 different countries, and a total of 31 different countries have joined this international coalition. We consider this coalition to be a major advance, and already many medical research interchanges have taken place that otherwise would not have existed.

The Cooley's Anemia Foundation helped to fund, along with the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, an international conference on Cooley's anemia research and medical care, under the auspices of the New York Academy of Sciences. It is the sixth such conference held every five years since 1961 and, by all measures, the most successful because of the rapid increase of new knowledge in the field. The NHLBI has pointed out that Cooley's anemia research has been a stimulus for basic biological studies of human genetics, having provided a great deal of fundamental information about the arrangement and function of the hemoglobin genes in humans. This information has been applied to studies of other disorders, such as diabetes, cancer and cardiovascular diseases, and has led to advances in bone marrow transplantation, drug therapy, and potentially gene therapy.

I spoke a few moments ago of the improved medical care for our patients resulting from medical research and from the chelating drug. Desferal that is a success story and is being proved over and over every day. For example, attached to this testimony is a news release issued today by our Foundation which states that for the first time in history, two of our patients have lived to 40 years of age. This is unprecedented. Before the research and care advances of the last decade, virtually all those afflicted died before their twentieth year. I personally am 25 years old and am on the Desferal regimen.

We ask your support, Mr. Chairman, for further research in the field of oral chelators, because we are on the verge of yet another major improvement in care. For over a decade, the National Institute of Diabetes and Digestive and Kidney Diseases has been experimenting with over 300 drugs, seeking an oral chelator, that can be taken by mouth in pill or powder form, which will do the same work as Desferal, that is, reduce the iron overload due to transfusions. At least five drugs now show such promise that they

are being studied in dogs, and it is estimated an extra $1 million will be needed to complete those studies.

Already, the National Heart, Lung and Blood Institute has shown great foresight by preparing a clinical trial protocol which is ready to go into action just as soon as clearances are obtained for human subjects to be tested.

In addition to this major opportunity for advance by means of the oral chelator, care advances are taking place also as a result of the Cooley's

We

anemia demonstration and treatment centers now in existence as a result of funding by the Maternal and Child Health Bureau's SPRANS program, that is, the program of Special Projects of Regional and National Significance. urge that the 15% set-aside, provided in authorization law, be appropriately funded to assure the continuation of this program; we hope that specific bill report language directing that will be approved by your committee.

Mr. Chairman, we are pleased to tell you that the Cooley's Anemia Foundation, from very small beginnings 37 years ago when there seemed to be no hope for adequate care, for increased longevity of our patients, much less for a cure, has worked hard to raise funds for research and patient care. Last year, for example, we awarded $300,000 in research fellowships for the 1990-91 academic year. Over the last five years we have awarded grants to more than 90 researchers, totalling over $1.5 million; to assure excellence we have utilized the peer review process modeled after that of the NIH.

All the matters I have described, including the oral chelator research, which has led to improved care (but unfortunately not a cure), are only a background to the profound advances now taking place in the research areas of bone marrow transplantation, which holds promise of a cure for a small segment of our patients, and gene therapy. We are very pleased that last year your committee gave such a strong push to these research areas and that you included patient organizations, such as ours, in the team effort to describe the long-range research plan.

We cannot say enough in support of the researchers and administrators of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung and Blood Institute, and the Maternal and Child Health Bureau, and we cannot thank you enough for the support that you have given.

Our recommendations for appropriations for fiscal year 1992 are:

NIDDK

$815 million (including an additional $1 million provided for animal studies on the oral chelator)

SPRANS (Maternal and Child Health Bureau) Reaffirmation of
support for the Cooley's anemia centers in the set-aside for
programs of regional and national significance.

NIH Overall

We support the Ad Hoc Group for Medical Research

Funding's recommendation of $9.770 billion.

Senator ADAMS. Thank you, Mr. Cazzetta. If you want to bring those forward, and then if Alan Brownstein, executive director of the National Hemophilia Foundation will come forward to testify, the Chair will take a 2-minute recess.

[A brief recess was taken.]

Senator ADAMS. The committee will come to order.

Mr. Alan Brownstein, executive director of the National Hemophilia Foundation.

[No response.]

Senator ADAMS. If Mr. Brownstein is not here, we will not skip him but we will come back to him.

STATEMENT OF DR. FRANCOIS ABBOUD, DIRECTOR, CARDIOVASCULAR RESEARCH CENTER, UNIVERSITY OF IOWA COLLEGE OF MEDICINE, ON BEHALF OF AMERICAN HEART ASSOCIATION Senator ADAMS. Dr. Francois Abboud, president, American Heart Association, and director of the Cardiovascular Research Center, University of Iowa College of Medicine.

Dr. Abboud, welcome.

Dr. ABBOUD. Senator Adams, thank you. I am here in my capacity as president of the American Heart Association and its 3.2 million volunteers.

Despite progress, cardiovascular diseases remain the No. 1 killer in the United States. Heart attack alone kills almost three times as many American women as breast and lung cancer combined. In the United States someone dies from cardiovascular disease every 32 seconds. One in four Americans suffer from it. The cost in 1991 alone was $103 billion in medical expenses in lost productivity.

The budget of the National Heart, Lung, and Blood Institute does not support essential new directions to deduce these catastrophes. The Senate Appropriations Committee directed NHLBI to plan multidisciplinary research in vascular diseases, sudden cardiac death, and congestive failure, but funds are needed for these implementations.

First, programs in vascular biology and medicine, these would provide a common ground for research not only on cardiovascular diseases but also lung diseases and blood-related diseases. Integration of blood vessel biology with blood vessel medicine improves clinical detection, treatment and, above all, prevention.

Second, sudden cardiac death remains a mystery. An abnormal heart rhythm causes 60 percent of heart attack victims to die in the first 2 hours. A specialized center of research would facilitate translation of knowledge into new treatment into lives saved from sudden death.

Third, congestive failure; 2 to 3 million Americans suffer from congestive failure. We stand on the threshold of new concepts. NHLBI funded only one score in the whole country. Additional centers are necessary for a critical mass of multidisciplinary research to be applied to the diagnosis and treatment.

The current budget would force NHLBI to again postpone a clinical trial on a new class of antihypertensive drugs to reduce heart attacks in men and women with mild to moderate high blood pressure. We have 60 million people with high blood pressure in this country, and a trial will reduce the incidence of heart attack in stroke and obese patients and will reduce health care costs.

Education. NHLBI is implementing the National Heart Attack Alert Program to educate health care professionals and patients about warnings of heart attack and the importance of prompt discovery and treatment. More than 300,000 Americans die each year of heart attack before reaching hospital centers. This program requires more support.

PREPARED STATEMENT

To end, the American Heart Association supports the ad hoc group for medical research funding proposal of $9.77 billion for the NIH. Within this figure, we recommend $1.33 billion to meet the critical needs of NHLBI to find the cause and prevent disease, and to reduce costs. It makes good programmatic sense; it makes good fiscal sense.

Thank you very much, Senator.

[The statement follows:]

STATEMENT OF DR. FRANCOIS ABBOUD

I am Francois Abboud, M.D., professor and head of the Internal Medicine Department, director of the Cardiovascular Research Center, University of Iowa College of Medicine, and president of the American Heart Association, AHA. It is my pleasure to talk about the foundation of our nation's health system, the National Institutes of Health, NIH.

The AHA is this Nation's largest voluntary health organization dedicated to the reduction of disability and death from heart and blood vessel diseases. Annually AHA's 56 affiliates nationwide coordinate the activities of about 3.2 million volunteers in carrying out this mission. Cardiovascular diseases, including heart attack and stroke, remain the leading cause of death in the United States, killing almost one million Americans each year. Heart attack alone kills almost three times as many American women as breast and lung cancer combined.

Since 1948 the AHA and the National Heart, Lung, and Blood Institute, NHLBI, have been active partners in the battle against cardiovascular diseases. Throughout this 43 year partnership the research, training, education, and community service programs of both the AHA and the NHLBI have had a significant impact. From 1978 to 1988 the age-adjusted death rate from coronary heart disease fell 29.2 percent and that from stroke fell 33.2 percent. This trend is largely attributable to advances in medical treatment, healthier lifestyles, and control of risk factors such as elevated blood cholesterol, high blood pressure, and smoking.

There is still a long way to go. In the United States someone dies from cardiovascular diseases every 32 seconds. More than one in four Americans suffer some form of these diseases.

In 1987 total cardiovascular disease accounted for 5.170 million years of potential life lost before age 75, followed by cancer and accidents. There will be even more cardiovascular disability because many people who have had effective treatment for coronary artery disease and prevention of atherosclerosis at age 40 to 60 will develop cardiovascular diseases later in life.

The estimated cost of cardiovascular diseases in 1991 will be $101.3 billion in medical expenses and lost productivity. Yet research investment at the NHLBI is $1.127 billion. Costs for patients with cardiovascular diseases grow because we are treating disease with expensive technology not preventing it.

Our ability to control cardiovascular diseases depends on the level and quality of overall support of basic and clinical research and prevention efforts. Since 1949, the AHA has invested over $900 million to support biomedical research. The size of this financial commitment makes the AHA second only to the federally sponsored NHLBI in the amount devoted to cardiovascular research. While we continue to devote an increasing share of our resources for research, much more is needed. Adequate federal funding for research is critical.

The steady decline in relative support for the NHLBI, as compared with the other institutes, is a major concern. Diseases of the heart, lung, and blood caused 53 percent of all deaths in the United States in 1989--despite major reductions in mortality attributable to research findings in the last decade. The NHLBI's allocation of funds among the NIH institutes should reflect a priority consonant with these major causes of death. The NHLBI's FY 1991 percentage increase over its FY 1990 appropriation ranked it 12 out of 13 institutes.

The Administration's FY 1992 budget allocates $1.210 billion for the NHLBI. This budget represents a 7.4 percent increase over the FY 1991 appropriation but does not support essential growth.

The NHLBI's program arsenal has been highly effective. The Institute's staff, Advisory Council, and scientific community pay careful attention to a balanced approach to the NHLBI evolving program structure. A high priority is given to research project grants, but the NHLBI stresses other program mechanisms such as clinical trials, population studies, specialized centers of research, SCORs, national research and demonstration centers, research career and training awards, research and development contracts, and education and direct prevention programs. This carefully balanced approach has contributed to the success of NHLBI programs and has enhanced its reputation as a worldwide leader in cardiovascular research.

The Institute's breadth of effective programs is exemplifed by research localizing a gene responsible for an inherited disorder, familial hypertrophic cardiomyopathy, FHC, (an abnormally enlarged heart or thickened heart muscle) one of the most prevalent causes of sudden death in young athletes; improving knowledge of the development of cardiovascular disease in American Blacks, and identifying obesity as a key, independent risk factor for coronary heart disease in women. Findings from these studies will provide significant opportunities for cost savings and for gaining new knowledge and treatment of cardiovascular diseases.

To continue progress against cardiovascular diseases, NHLBI has planned important new activities for FY 1992. As directed by the Senate Appropriations Committee's FY 1991 report, the NHLBI continues to plan multidisciplinary research on blood vessel (vascular) diseases, sudden cardiac death and congestive heart failure. NHLBI funding must be sufficient to adequately support on-going research and to expand into these and other emerging areas.

Cardiovascular diseases impact a wide field of health problems, including coronary heart disease and stroke--both noted for high incidence, serious morbidity, significant mortality, and great expense. About half of all deaths in the United States are caused by vascular diseases. Coronary heart disease and stroke claim over 500,000 and 150,000 deaths, respectively, each year. Approximately six million Americans suffer from coronary heart disease and 2.9 million have survived stroke. Pulmonary embolism is associated with about 150,000 deaths each year. Thickening of the right ventricular wall, resulting from pulmonary hypertension (high blood pressure in the lungs), accounts for 6 to 7 percent of adult heart disease.