Chapter 10: Dr. Jan VanEys and the Development of MD Anderson’s Code of Ethics; Working with Pharmaceutical Industry

Title

Chapter 10: Dr. Jan VanEys and the Development of MD Anderson’s Code of Ethics; Working with Pharmaceutical Industry

Files

Loading...

Media is loading
 

Description

In this chapter, Dr. Gehan talks about Dr. Jan VanEys’ work in pediatrics and as an ethicist at MD Anderson. He mentions Dr. VanEys’ work with Dr. James M. Bowen in the creation of a code of ethics at MD Anderson. He then talks about the role of statistics in cancer research, cancer research ethics, and the ethical use of randomized trials. He goes on to reference Donald “Don” Arthur Berry, head of the Department of Biostatistics at MD Anderson, talks about clinical equipoise, contrasts Bayesian and Frequentist reasoning, sequential analysis, randomized trials, etc. Dr. Gehan talks about the statistics department’s working relationship with other areas at the institution including working with Dr. Charles Blach who was the Head of the Department of Surgery at the time. Before 1980, the National Institute of Health (NIH) funded most research. Changes in the industry saw a bulk of funds coming from drug companies, which required new logistical concerns regarding data management and patient participation numbers to justify expenses. He provides examples of Dr. Bodey's research in protective environments for cancer patients.

Identifier

GehanE_01_20030328_C10

Publication Date

2003

Publisher

The Historical Resources Center, Research Medical Library, The University of Texas Cancer Center

City

Houston, Texas

Topics Covered

The University of Texas MD Anderson Cancer Center - An Institutional Unit; Building/Transforming the Institution; Ethics; The Business of MD Anderson; Critical Perspectives; The Professional at Work; On Research and Researchers; Understanding Cancer, the History of Science, Cancer Research; Ethics; Industry Partnerships; On Pharmaceutical Companies and Industry

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Lesley W. Brunet:

I notice you didn’t mention Dr. VanEyes.

Edmund A. Gehan, PhD:

I didn’t mention Dr. VanEyes. He is the ethicist, right?

Lesley W. Brunet:

He was a pediatrician.

Edmund A. Gehan, PhD:

His research interests were in ethics, and I think it may well be that there is still sort of the ethical guidelines at M. D. Anderson. I believe that may be so. He formulated them or I think he was very instrumental in that.

Lesley W. Brunet:

He and Dr. Bowman (?)

Edmund A. Gehan, PhD:

I am one hundred percent for ethics. Who is against it? But I would be hard-put to say how the headship of pediatrics helped in the prevention or treatment of pediatric cancer patients. I think he had a certain special area, which he pursued. I guess one point that I would make, not in relation to Dr. VanEyes, is that statistics have helped to provide quantitative ways of dealing with ethical problems, this notion of a sequential trial comparing treatment A to treatment B. You begin randomizing patients and the study goes on, and you start to accumulate data and the data will tend to favor one group or the other. I think we mentioned briefly this morning, when is it ethical to randomize patients? I think the ethical argument is when there is clinical equipoise, when the chance for benefit, as far as is known, is equal on both treatments. We really don’t know which of these treatments is better. We have some previous data. We want to do this study to find out. OK, we do this study and I think I can show you that data problem. Things like this have happened. [I have] a pretty good friend here, Don Berry, who is now head of Biostatistics. I have heard that he gives a talk something along the following lines. It is a randomized double blind clinical trial. The data have started to come in. Here are the first four patients. Three of them favor 6MP in terms of length of remission. Do we still have clinical equipoise? They are three to one. We are still randomizing patients, we are still saying the next patient has a fifty-fifty chance for 6MP or placebo. Let’s keep going. Oop. Placebo. We keep on. I have heard people give a talk to the audience and say, OK, well now it’s eight to two. Shall we keep going? Would you be willing to be randomized? Now it’s ten to two. Oop. There is a lot of evidence in favor of 6MP. Don Berry is a Bayesian, which we haven’t really talked too much about.

Lesley W. Brunet:

Bayesian?

Edmund A. Gehan, PhD:

Bayesian. It gets into a philosophy. This study was planned from a sequential viewpoint, but it was using the frequentous philosophy, and I don’t think we’ll have enough time to explore that, but this study was planned and it was based upon the number of preferences for 6MP minus the number on placebo. The way the actual trial ended, but it was planned from the beginning this way, was at the eighteenth one. At that time there were fifteen preferences for 6MP and three for placebo. Now if one takes a different philosophical approach, this Bayesian approach, and if you want to learn more about that…

Lesley W. Brunet:

I’m going to look it up.

Edmund A. Gehan, PhD:

You could ask Don Berry to come over here and tell you. I have never actually heard him give this talk, but there would be a way of incorporating [this]. Suppose you said at the beginning, “I think 6MP and placebo are equal.” You don’t have any prior preference. But the Bayesian incorporates the evidence so with each successive pair of patients, what is the evidence now that 6MP is better than placebo? Using the Bayesian approach, you would have stopped earlier than here, but we didn’t use the Bayesian approach. This was planned in 1959 (Reference ?), something like that. The general point that I was making is sequential analysis provides a way of giving quantitative weight to the evidence favoring treatments. Yes, it was ethical at the beginning to randomize, but as data are accumulated the statistical idea of sequential analysis is to permit you to stop the study and declare one treatment significantly better than another based upon the evidence. In a way, I think that statistics is a way of quantifying ethical statements.

Lesley W. Brunet:

(Inaudible) The Statistical Department’s Work at MD Anderson, NIH Versus Pharmaceutical Company-Funded Cancer Research, Data Management and Drug Testing/Reporting ?: An Story Codes ?: Building/Trans

Edmund A. Gehan, PhD:

02:11:19.480 I didn’t work with Dr. VanEyes. As I said, we did not tend to go out and knock on people’s door [saying] do you have anything that needs statistical help? We were responsive. I did work with Dr. Balch when he was head of surgery. They had a research committee within surgery and I guess this was after Dr. White was here. I think he was interested in research, and he had come from, I believe, the Southeast Group in Birmingham. I was on a committee and went to certain meetings, but it didn’t develop as far as it might have. Our group in biostatistics collaborated with people who called upon us.

Lesley W. Brunet:

02:12:43.970 At one point in 1980, I saw a letter where Dr. LeMaistre was recommending that all grants, contracts, and arrangements with pharmaceutical companies be required to have a solution overhead to support data collection process. Is that the statistical side?

Edmund A. Gehan, PhD:

Support the data collection process… All protocols?

Lesley W. Brunet:

Just that the grants, contracts and arrangements with pharmaceutical companies (? Counter 171) external support for the data process. Was that your work?

Edmund A. Gehan, PhD:

Do you have a precise quote on that?

Lesley W. Brunet:

I just had a note (Dr. Gehan talked over you…)

Edmund A. Gehan, PhD:

He was not talking about statistics. I think he is talking about data management. A lot of the pharmaceutical companies, and this is a trend that has taken place, is that more of the pharmaceutical company “X” comes not only at M. D. Anderson but to many other places. We would like this drug tested in certain kinds of patients, and we are willing to pay you “X” dollars per patient to get this done. They may want to submit the results of this trial for registration at the FDA [Food and Drug Administration]. So there are fairly rigid reporting requirements for this. They really need a lot of detail data to accomplish that, and I think my reading between the lines of that is that before this, we are going to give you maybe $1,000 a patient, which sounds like a lot of money. On the other hand, when they say, here are the forms that you have to fill out, then there would be the follow-up of the patient after they leave. This is quite an expense, too. It looks to me like a reaction saying that, “Look it should be more than $1,000 a patient,” roughly speaking.

Lesley W. Brunet:

Yes.

Edmund A. Gehan, PhD:

But it would have nothing to do with statistics. Those trials are planned by the pharmaceutical companies. M. D. Anderson is big enough so that they may try to do the whole trial at M. D. Anderson. Georgetown is not as big as M. D. Anderson. (? Counter 213) does say, we’re going to do this study at ten sites, of which M. D. Anderson might be one and nine others. They are more or less drug testing, for which they should make enough money to make it worthwhile. They are working for the pharmaceutical companies. If you can get a copy of Dr. Rowinsky’s slides, he had let’s say before 1980, a lot of the therapeutic research is sponsored by NIH and the government, but now the pharmaceutical companies are doing most of it. I think that was a reaction saying M. D. Anderson should be sufficiently well paid to do this kind of work from the data reporting sense.

Lesley W. Brunet:

There did seem to be sort of a reduction in some of the contracts in 1980, for example the protective environment federal contract was reduced and then ended in 1981 and I didn’t know why. (Dr. Gehan coughed) Was that part of the events in 1981?

Edmund A. Gehan, PhD:

One of the things I did was re-read this (Reference ?). It was easy to do at the time. One of the references is to the protected environment study. I guess what I have heard… Have you interviewed Dr. Bodey?

Lesley W. Brunet:

I am interviewing him on Monday so that’s why I am pumping you now.

Edmund A. Gehan, PhD:

Well, you ask him about this, but protected environments are tremendously expensive. They are very expensive. I think the story you are going to hear from Dr. Bodey is that the administration here was never enthusiastic about studies of this type because it was simply too expensive.

Lesley W. Brunet:

Was this the Clark administration or the LeMaistre?

Edmund A. Gehan, PhD:

I think it was LeMaistre. Actually what I remember re-reading here is a statistical approach to dealing with a protected environment study. We did publish a paper with Dr. Bodey, “Protected environment, prophylactic antibiotic program in the chemotherapy of acute leukemia” (Reference ?) Dr. Bodey had been entering patients. I think there were thirty-three patients entered into the protected environment, and was this good for the patients or bad? It wasn’t a randomized study, and actually I argued before that some of the studies shouldn’t be necessarily be randomized. This wasn’t done conscientiously in this way, but I think there are good arguments for not doing a randomized study. One of the arguments being these environments are tremendously expensive. If are going to randomize a patient, fifty percent, this patient goes into the environment or he doesn’t. If he doesn’t, then that room is empty. (Laughter) That’s costing us a lot of money, even if it’s empty. So it is in our financial interest to keep that room like the airplanes—keep them in the air. But that’s what he did, he just entered patients. He worked closely with Terry Smith and myself and we found a group of patients that didn’t go into the protected environment around the same time, and we found ways of finding for this patient that went in, a potential pair-mate for that patient with certain characteristics such as age, sex, infection status, white blood count, platelet count, time from diagnosis to therapy, and previous therapy. All of those features would affect your subsequent outcome. We found possible pair-mates from among each of the thirty-three patients that went in. Then in a double-blind way, [we] said to Bodey, here is a list of six patients. We’re not going to tell you which one actually went into the [protected] environment. You rank these patients in whatever way you think, which one has the best chance, and so he might rank the protected environment patient number three. Then we would pick number two as the pair-mate, the more favorable one. This is a way of finding comparable patients, as comparable as we could find them. In the end, analysis was done of the thirty-three that went into the environment versus—actually we did sixty-six. We found two pair-mates, and this was kind of a statistical argument. We said, well Bodey’s hypothesis is the protected environment is good, so the protected environment patients should be doing better than the ones that didn’t go in. However, we’re going to put two pair-mates and neither one of those will have gone into the [protected environment]. One way of justifying this study is if the protected environment patient did better, but that the other two pair-mates did the same, that there was essentially no difference between them and that is exactly what happened. The protected environment patients did ten to fifteen percent better in various measures. The pair-mates, choosing two controls for each patient, weren’t different from each other. I think one could argue that if it’s ten to fifteen percent better in terms of survival rate in various measures, is it worth it?

Lesley W. Brunet:

(Dr. Gehan talks over your question.)

Edmund A. Gehan, PhD:

We were just concerned with what is the weight of the evidence in favor of one or the other. Bringing the cost into play, that’s another whole issue. I think they thought it was too expensive. If you’re interviewing Bodey…

Lesley W. Brunet:

I’ll ask him about that. (Dr. G talks over you).

Edmund A. Gehan, PhD:

There can be psychological problems for the patients, too, if you’re completely isolated.

Conditions Governing Access

Open

Chapter 10: Dr. Jan VanEys and the Development of MD Anderson’s Code of Ethics; Working with Pharmaceutical Industry

Share

COinS