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Dr. Cox. I can say that I believe the only way of being fair is to judge them by the standards of the time, not the standards of today. To do otherwise would be to treat them unfairly.

To judge cancer treatments of the time by the standards of today would be to judge them unfairly. We have evolved. Medicine has evolved and the process of informed consent has evolved.

Mr. BRYANT. You mentioned the studies reviewed by the Faculty Research Committee of the Cincinnati University College of Medicine.

I think it is fair to say we might set that aside, inasmuch as they are, I would think, an interested party.

Dr. Cox. I would take exception to that, sir. I believe that that is the title for what we would now call the Institutional Review Board, and that that is a standard part of the review process.

As a matter of fact, key to the review process to this day. So I was interpreting that as being a specific term for the general term of what we would call the IRB or Institutional Review Board, and that is absolutely critical to this, but the standards have changed relative to the IRB today relative to what they were then.

Mr. BRYANT. I agree we should stick to the standards at the time in judging everybody's intent at the time. You say they were also reviewed by the National Institutes of Health. We have now found that apparently they refused to participate in this. Is that relevant?

Dr. Cox. I took that from the footnote to Dr. Saenger's paper of 1973, where it said that this was supported in part by the Department of Health and Human Services. I don't know any other agency that would have supported it in whole or in part except NIH at that time.

Mr. BRYANT. What do you mean by support? Dr. Cox. IMr. BRYANT. You mean help pay for the research? Dr. Cox. I assumed that is what it meant. Is it possible that the NIH approved and supported this for a period of time and then withdrew its support?

I don't know the answer to that, but I was just going by what was included in the publication. You will have to ask others.

Mr. BRYANT. We are asking others, but this reference that you made on page 4 of your testimony, and is in the list of things which you characterize as peer review.

My question is, if this matter underwent peer review by the National Institutes of Health, it is a fair question for us to ask how it could be that they did not participate. There is indication they didn't participate, and at the same time came back and gave this a clean bill of health in the peer review process.

Dr. Cox. I made that statement based on this quote from Dr. Saenger's paper of 1973: "Supported in part by USPH RR-5408, NIH General Research Support Grant of the College of Medicine in Cincinnati.” Maybe the grant was through the University in a broad sense and not specifically to this project. But it would have undergone review by NIH as a part of the review of the University of Cincinnati's grant from NIH.

Mr. BRYANT. Have you seen a review of this that went back to judge whether or not it was handled in a proper way?

Dr. Cox. No.

Mr. BRYANT. So I wonder if it is appropriate that you list it under peer review in your testimony here. Perhaps you are just assuming they would have reviewed it if they had a role in it, and now we doubt that they even had a role in it.

Dr. Cox. I am just taking it from the publication that is that is where that came from. I took it from the quote in the publication by Dr. Saenger's report, Dr. Saenger and colleague's report from 1973.

Mr. BRYANT. Let's go to the one conducted by the American College of Radiology at the request of Senator Gravel in 1972.

Would that have taken place over the telephone? Would that have been everybody exchanged written data and read it over in their office, or would that mean a visit to Cincinnati? What would that mean?

Dr. Cox. From the report that I have, which I really only have two documents that serve as background for this, one is Dr. Saenger's paper, the one is the report from Drs. Kaplan, Hendrickson and Taylor, through the American College of Radiology, to Senator Lavelle.

In that report, they indicate that they first had a preliminary meeting in Chicago, and after that paid a site visit to the University of Cincinnati and reviewed records, discussed with a wide variety of people here, and did that which we would consider standard for a site visit today and they did it in the context, as they wrote, of what they would consider a study section or a peer review at NIH at that time.

So they were approaching it as if they were peer reviewers, as they would review any grant that had been submitted to them for review at NIH. They were all experienced reviewers. So they both reviewed the documents and they paid a site visit.

Mr. BRYANT. Any further questions?

I would like to thank all the panelists, particularly Dr. Soper and Dr. Cox who traveled a long way, and Dr. Steger and Mr. Chesley for taking your time in coming forward and helping us in this inquiry.

Thank you very much.

At this time, the committee would invite the third panel to come forward, which consists of Dr. David Egilman, clinical assistant professor, Department of Community Medicine, Brown University; and Dr. Martha Stevens, professor of English at the University of Cincinnati.

We thank both of you for being here today. As with the other witnesses, we ask you to hold your opening statement to five minutes so that we might go right to the questions.

We will start on the left of the committee, Dr. David Egilman.

STATEMENT OF DAVID EGILMAN, M.D., CLINICAL ASSISTANT

PROFESSOR, DEPARTMENT OF COMMUNITY MEDICINE, BROWN UNIVERSITY

Dr. EGILMAN. Chairman Bryant, committee members, thank you very much for inviting me here. I am a private physician, practicing in Braintree, MA. I am on the faculty at Brown University.

I teach a course on the development of medical and scientific knowledge and history of the 20th century that includes the issue of the development of ethical standards during that time.

For 10 years or so, I have been trying to get the research funded by our Government on its own citizens that was performed here and at other institutions for purposes of military research investigated. I appreciate this opportunity today.

I want to begin first by responding to a question that was asked of the previous panel. Dr. Cox was asked whether or not he could find confirmatory evidence of informed consent in the 1973 paper. Well, there is some evidence on page 678.

It says, The acute radiation syndrome develops in stages. In the prodromal stage, nausea and vomiting of a transient nature occur. These complaints are not discussed with the patient before treatment.

The comments I make are not a retrospective look at the 1960's by 1970's standards or 1980's standards or 1990's standards. They are rather a look at the 1960's and 1970's by the standards of the 1890's, the 1940's, and the 1950's. As I begin with comments of physicians who reviewed this research for the University of Cincinnati, on the faculty of the University of Cincinnati, at the time the work was going on, that will be clear.

Dr. Gall, first in 1966, in a letter, stated that the informed consent form was inadequate. Dr. Shields, also writing about the informed consent form, in 1967, wrote “I believe a 25 percent mortality is too high.” He also made a small comment about the adequacy of the therapy for cancer. "All patients should be informed not only that a risk exists, but of a one in four chance of death within a few weeks of treatment."

Evelyn Hess, writing in 1969, stated "The acceptability of our general consent form for human volunteers participating in research was questioned."

Dr. Thomas Gaffney, in 1967, wrote: The applicants have apparently already administered 150 to 200 rads to some 18 patients with a variety of malignancies and to the researcher's themselves' satisfaction, have not found a beneficial effect. In fact, as I understand it, they found considerable morbidity associated with this high dose of radiation. Why is it now logical to expand this study? Its current design will not yield meaningful data. The study should not be done.

Dr. Gaffney was on the faculty of the University of Cincinnati reviewing these experiments. But the ethical standards were known and established long before, with reference to this type of an experiment.

In 1950, Dr. Hamilton wrote describing similar work to Dr. Shields Warren, and said that this type of experiment had a little bit of the Buchenwald touch.

My father was at Buchenwald. I can assure you by 1950 it was well known what it meant to say that an experiment had a little of the Buchenwald touch.

The subjects were uneducated, had poor education, low IQs, and many had brain dysfunction because of their disease. They were unable to give informed consent. Rose Strom was diagnosed as resectable sarcoma in April 1970. She received a course of chemotherapy.

Chemotherapy was given for colon cancer in this time period. It was and still is to date palliative therapy for colon cancer. She was readmitted to the CGH on December 14, 1970.

According to Mrs. Strom's records, at 2 p.m. on that date, she received 10 milligrams of morphine IM, intramuscularly. Also at 2 p.m. she signed a consent form for radiation. She was then irradiated.

This was immediately followed by nausea and vomiting that lasted for 3 hours. She vomited repeatedly for 3 days. Antinausea medicine was withheld until the staff noted she was depressed to the point of crying and that she said, “I am so sick.”

Withholding therapy for nausea and vomiting is not then nor is it now part of normal cancer treatment.

The researchers knew that informed consent was the standard of the day. As you have heard in the paper we read, they claimed they received informed consent. Despite that fact, only six of the first three patients received any information on the nature of the experiment, and none were informed of possible risks. If their published papers correctly report their failure to advise their patients about the possible experimental risks, their stated conclusion that they received informed consent is surely wrong.

The researchers were aware of informed consent requirements. They said they met the informed consent requirements of the Helsinki Code published in 1962. Similar experiments were rejected by one of the researcher's colleagues and when advised of the research in 1966 when it was suggested that the same thing be done at Oak Ridge University.

Oak Ridge researchers said, we are hesitant to treat these cancers because we believe there is so little chance of benefit to make it questionable ethically to treat them. Lesions that require moderate or a high dose of local therapy for benefit or are actually radio-resistant such as gastrointestinal cancer, just to help Dr. Cox, are not helped enough by total body irradiation to justify the bone marrow depression that is induced.

The argument that these experiments were appropriate from the ethical standards of the 1960s lack both scientific and historic accuracy.

In addition, cancer therapy was not the purpose of this research. Previous research had already been done. In 1942, it was published, “Little or no benefit follows its use,” that is radiation, whole body radiation, "in the treatment of generalized carcinoma or sarcoma."

That is the kind of cancer in this study. “In no patient was there evidence that total body irradiation affected disease, 1965.” In the kinds of cancers in this study.

Cancer therapy was not the purpose of the research. The researchers themselves described the purpose of the research: “To provide knowledge of combat effectiveness of troops.” In real medical research, in real therapy, treatment for nausea and vomiting is provided. In military research in the U.S. experiments, it was denied until the patients had severe nausea and vomiting.

In real research, in real cancer therapy, psychologic and peer counseling is provided. In this work, in this military research, in

these U.C. experiments, patients were intentionally psychologically isolated.

In real medicine, in real radiation therapy, the radiation is given slowly and from many directions to improve effect and reduce side effects. In military research, in these experiments, the radiation was given fast and unidirectional, in the words of the researchers, because that was the radiation of military interest.

On February 9, 1971, Mr. Willard Larkins was noted to either have a lymphoma or adnocarcinoma of the colon. According to the hospital notes written by Dr. Aron and Dr. Rau, if he had a lymphoma, radiation would be indicated, while if an adnocarcinoma chemotherapy would probably be in order."

On February 19, Mr. Larkins was found to have adnocarcinoma and Dr. Rau said, “Radiotherapy was definitely out of the picture and the patient may be a candidate for 5FU.” 5FU is chemotherapy.

Five days later, he got the radiation. He never got the chemotherapy. There were four or five informed consents signed in Mr. Larkin's chart for surgical procedures. There was no informed consent signed for radiotherapy like this.

This was 1971, well into the period where people claim all the patients signed informed consents, well into the period when people claim the standard was a signed informed consent should be given.

Who was responsible? I think we find here we still have a problem. The fact that the representatives of the ACR, admittedly apparently from an institution that did similar work, could still come here and claim that this work was appropriate means that we have a problem in the medical community in this country. It is a problem that is a current problem. It is not an old problem.

The fact that there is an attempt to let you think that this was in some way not previously found to be inappropriate therapy means we have a problem in this country.

It is in the medical community. The fact that the University of Cincinnati's report reported almost everything I said and then said they had no problem means that there is a problem at the University of Cincinnati and at other universities. The fact that NIH denied the funding and then didn't tell anybody it was because of ethical reasons means we have a problem.

Thank you.
Mr. BRYANT. Thank

you.
[The prepared statement of Dr. Egilman follows:)

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