5

6

5

time and in such form as the Secretary may require and

not less than four times a year. Each and every prescrip

tion submitted to the Secretary shall contain both the

attending physician's license number and the name of

the State which issued such license number.

"(2) (A) For the purpose of this subsection an 'in7 formed consent form' means a form issued by the Secretary 8 and approved by the National Commission for the Protection 9 of Human Subjects of Biomedical and Behavioral Research (hereinafter in this subsection referred to as the 'Commis11 sion') and is fully explained by the attending physician to 12 the patient and is thereafter executed by the attending 13 physician and patient or the patient's legal guardian. If the

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Commission fails to take action within sixty days after the Secretary submits the proposed informed consent form, it shall be deemed approved.

"(B) Drug producers shall not be held liable for misbranding under subsection (g) (1) (D) and (E) of this

section.

"(C) No patient names or other identifying information shall appear on any informed consent form, prescription, or

report submitted to the Secretary. No patient name or other

identifying information shall be submitted to or collected by

the Secretary.".

Mr. ROGERS. Our first witness this afternoon is our distinguished colleague, the Honorable John Melcher of Montana, who has, as I understand it, an experience that can be helpful to the committee. We are very pleased to have you here, Congressman Melcher, and I am sure that the subcommittee will benefit from your testimony. You may proceed as you desire.

STATEMENT OF HON. JOHN MELCHER, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF MONTANA

Mr. MELCHER. Mr. Chairman and members of the subcommittee, I was not aware of the subcommittee's intent to only consider the aspects of human use of DES, rather than the use in animals.

Mr. ROGERS. I understand that. That is perfectly all right. You may proceed as you desire.

Mr. MELCHER. Thank you. I have a short statement, and I will read it.

Diethylstilbestrol (DES) is a proven carcinogen. It causes cancer. There has to be a determination of how much has to be ingested over a period of time before cancer develops. The National Cancer Institute has suggested that its use as a cattle growth stimulant be immediately withdrawn from the market; that even the small amount of DES residue found in beef liver is sufficient evidence that the U.S. public is in some danger.

For the cattleman, the question is not just an economic one. It is also a question of consumer confidence. As a veterinarian and former feedlot operator, I have used DES as a growth stimulant in the feedlot ration and understand its beneficial aspect as such. It does promote growth. It does save on feed costs. And it does help get our product to market faster. That there are economic advantages when seen on paper cannot be disputed.

However, there is a much more important matter at stake than the economics of raising cattle. That, of course, is the consumer's fear of eating meat from animals fed a known carcinogen. While research indicates that a human would have to eat a huge amount of liver containing DES over a long span of years-perhaps more than a lifetime-consumers fear that beef from cattle fed DES is dangerous. They consequently buy less, or none at all, to the serious economic injury of the industry-an injury that offsets DES's value as a feed additive.

Cancer researchers have spent billions of dollars trying to isolate and determine what causes cancer. In their research, they have been able to identify many carcinogens and have been successful in seeing that their use be expediously discontinued. DES is a different case. The Food and Drug Administration, recognizing the danger of the chemical, has tried in vain for several years to ban its use in cattle feed. Other countries, also recognizing the possible threat, have not only banned it in their own cattle operations, but have refused to import our beef because, in their opinion, we have been negligent in allowing continued use of DES.

Through my own experience and my observations of other cattle operations in my area of Montana, I believe that after an initial adjustment period, following an overall ban of DES, the cattle industry

would be as well off as it is currently. We will have no difficulty in maintaining beef output by feeding cattle on grass for longer periods and by putting them into feedlots later than is currently done. The price of beef would not rise appreciably and, in the long run, I believe that consumers would rather pay 3 to 4 cents per pound more for beef which they are confident has come from cattle not fed DES.

In summary, the use of DES in the feedlot ration is a poor policy. As long as there is any chance of residue being retained in the liverand there is a chance-consumer confidence in the wholesomeness of the product will be jolted. I believe DES should be unconditionally banned in livestock feeds. There is no way to rationalize economic gain brought about by the use of DES in view of even the remote chance that it may cause cancer in human beings.

I commend Senators Kennedy and Schweiker for their dedicated efforts in seeing S. 963 through the Senate, and wholeheartedly support it and the companion bills now being heard in this committee.

Mr. ROGERS. Thank you very much. Your statement is most helpful, particularly so with respect to your background. The committee is appreciative of your interest in being here and certainly will weigh the evidence you have given it.

Mr. Preyer.

Mr. PREYER. I want to join the Chairman in thanking you, and I agree that there is no one in Congress that knows more about your subject than you, Mr. Melcher. We certainly appreciate your testi

mony.

Mr. ROGERS. Dr. Carter.

Mr. CARTER.Thank you, Mr. Chairman.

Certainly I appreciate your statement. I feel that you are speaking for the benefit of the people of the country and not for yourself, since you have been a feedlot operator. I personally appreciate your testimony, and thank you.

Mr. MELCHER. Thank you.

Mr. ROGERS. Thank you so much. The committee expresses its gratitude.

The next witness is Dr. Alexander M. Schmidt, who is Commissioner of Food and Drug, Department of Health, Education, and Welfare. We welcome you to the committee, and your colleagues. Mr. Merrill, we welcome you. We will be pleased to receive your testimony. Your statement will be printed in the record, and you may proceed as you desire.

I think it might be well for the reporter of the committee if you would identify your associates.

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STATEMENT OF ALEXANDER M. SCHMIDT, M.D., COMMISSIONER, FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, ACCOMPANIED BY RICHARD A. MERRILL, CHIEF COUNSEL, FDA; ROBERT TEMPLE, M.D., ASSISTANT TO THE DIRECTOR, BUREAU OF DRUGS, FDA; ROBERT C. WETHERLI, JR., DIRECTOR, OFFICE OF LEGISLATIVE SERVICES, FDA; AND BERNARD H. ST. RAYMOND, M.D., GROUP LEADER, OB/GYN DRUGS, DIVISION OF METABOLISM AND ENDOCRINE DRUG PRODUCTS, OFFICE OF NEW DRUG EVALUATION, BUREAU OF DRUGS, FDA

Dr. SCHMIDT. Thank you, Mr. Chairman and members of the subcommittee.

I am accompanied today by Mr. Richard Merrill, Chief Counsel of the Food and Drug Administration on my immediate right, and beyond him is Mr. Robert Wetherell, Director of the Office of Legislative Services.

Mr. ROGERS. We welcome you.

Dr. SCHMIDT. On my immediate left is Dr. Robert Temple who is Assistant to the Director, Bureau of Drugs; and on his left, Dr. St. Raymond, who is group leader of the OB/GYN Drug Group in the Division of Metabolic and Endocrine Drug Products.

Mr. ROGERS. We welcome you.

Dr. SCHMIDT. I would like to submit my full statement for the record [see p. 14] and extract from it parts that are relevant to today's subject, and not repeat some of the things that have already been said. I will begin my statement on page 2, and begin by mentioning the use of DES as a human drug.

As you have mentioned, Mr. Chairman, DES has a long history of effective use in human medicine. It is now approved for the following conditions:

Replacement therapy of estrogen deficiency associated with menopausal syndrome, female hypogonadism, amenorrhea, castration, or primary ovarian failure;

Control of functional uterine bleeding in the absence of organic pathology;

Relief or prevention of engorgement of the breasts in the postpartum period; and

Palliative therapy in the treatment of carcinoma of the prostate in the male and carcinoma of the breast in postmenopausal women.

DES has had another important use in the past. It was widely used in women during the 1950's and 1960's in an attempt to prevent spontaneous abortion, a purpose for which it is not effective. În 1971, Herbst and coworkers reported that the female children who had been exposed in utero to DES had a far greater than normal tendency to develop cancer of the vagina. This finding has been the basis of FDA's requirement that use of DES during pregnancy be contraindicated. It has also, quite properly, focused attention on the potential harmful long-term effects of estrogen use, particularly DES use. At the present time, however, there is no evidence that the mothers treated for threatened abortion had an increased likelihood of developing cancer.

APPROVAL OF DES AS A POSTCOITAL CONTRACEPTIVE

In the midsixties, several reports, including those by Morris and van Wagenen and by Kuchera, indicated that DES prevented pregnancy when administered in large doses immediately following intercourse. It subsequently became apparent that widespread use of DES as a postcoital contraceptive followed the publication of these reports. DES is a generic drug and is made by many manufacturers, none of whom came forward with data to support the use of DES as a postcoital contraceptive. FDA recognized that widespread use of DES for this purpose without assurance that the use was effective and, even if it was effective, without labeling providing adequate directions for use could pose safety problems for patients. Therefore, on its own initiative, that is without any application for marketing approval before us, the FDA addressed this problem.

Medical and scientific journals over the past decade had carried reports on the safety and effectiveness of DES as a postcoital contraceptive and described significant use of the drug for this purpose. We, therefore, determined to consider the published data without an industry application through established procedures for public decisions, namely, public discussion before our Obstetrics and Gynecology Advisory Committee and the publication of regulations in the Federal Register.

The basic published information relating to the safety and effectiveness of DES for this use was reviewed and presented to the advisory committee by representatives of the National Institute of Child Health and Human Development. The action eventually agreed upon was developed in collaboration with the advisory committee, was published for comment in the Federal Register on September 26, 1973, and was later modified on the basis of these comments.

In deciding to address the problem of DES for emergency postcoital contraception. an important example of widespread use of a drug for an unapproved use, we had four options:

1. Do nothing, that is, ignore the use of DES as a postcoital contraceptive on the grounds that no application was presented to us. We considered this option as irresponsible, in view of the widespread use and the safety issues involved;

2. Withdraw approval of DES as a drug. While some persons favor this position, no convincing case was ever developed by the responsible FDA staff or the advisory committee, and this option was not exercised.