Chapter 04: A Philosophy of Clinical Research (and Its Early Controversies)
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Description
Dr. Buzdar first sets his philosophy of clinical research in the context of his early work on aggressive chemotherapies. He says that a principle investigator should always be honest with the patient. [The recorder is paused.] The "gold standard," he says, is full information. [The recorder is paused.] Dr. Buzdar notes that there was almost a "cult" attitude at the time that the best procedure was to push more drugs at higher doses, without evidence that this had an impact on outcomes. He notes that he was chair of the institutional review board at the time. He then notes that MD Anderson was the first institution to add taxanes to the FAC regimen, a combination that is still standard of care.
Identifier
BuzdarA_01_20170210_C04
Publication Date
2-10-2017
Publisher
The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - Overview; The Researcher; Research; Discovery and Success; Healing, Hope, and the Promise of Research; MD Anderson Impact; MD Anderson Impact; Institutional Politics; Controversy; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Ethics; Research
Transcript
Tacey A. Rosolowski, PhD:
Now, this really goes to the heart of an issue about clinical research, and a kind of philosophy about clinical research. I've talked with a number of people about this, you know, where are those ethical lines and what -- so what is your perspective on pretty aggressive studies of this kind, that may throw a patient into a questionable situation? How were you thinking about that at the time and how do you think about that now?
Aman Buzdar, MD:
I think now, because that is one of my -- I am the institutional person who is responsible for all clinical research.
Tacey A. Rosolowski, PhD:
Right, right.
Aman Buzdar, MD:
My thinking at that time was the same as it is today, because the thing is, as a research participant, you have to be honest with the person who is sitting in front of you. What do we know today? What is their outcome with today's treatment? Why are we testing this, and what we think may happen? You have to also tell the participant, We think that --this is what we think may help, but we don't know. You are -- you have to be very honest with the patient, that you are at the cutting edge of the science. This means that you are going in undefined areas of medicine and you are trying to define the new boundaries of medicine. I still believe, every time I sit with a new patient or a patient who needs treatment or research, -- [Interruption].
Tacey A. Rosolowski, PhD:
Should I pause the recorder?
Aman Buzdar, MD:
Yeah. [Pause in recording]
Tacey A. Rosolowski, PhD:
All right. So, you were talking about the importance of being completely honest, that the patient is on the cutting edge of research.
Aman Buzdar, MD:
And the patient had to make a decision with your help, but you have to give the participant a total picture. What is known, what is the outcome with the standard treatment, why you are doing this research, what are the potential risks, and what we think may be potential positive things if it works out. You have to be very honest with the patients and the participants, that we don't know. If we knew, it will be a known medicine, it won't be research.
Tacey A. Rosolowski, PhD:
Right, exactly, exactly.
Aman Buzdar, MD:
And that is still the gold standard. We give patients full information and full autonomy of the human subjects, that's the guiding principle for doing research.
Tacey A. Rosolowski, PhD:
Now at the time, I mean in the mid-'70s, when you were here, it was kind of learning on the job, about all of this. You were kind of establishing all of this framework and what were -- were there other prevailing"¦ Let me just let you look at that. [Interruption from phone]
Aman Buzdar, MD:
Let me just take a look.
Tacey A. Rosolowski, PhD:
Sure. [Pause in recording]
Tacey A. Rosolowski, PhD:
So, how long did it take, you know, starting from that time in the mid-'70s, how long did it take for the controversy about all of this to settle down and for people to come to a shared view of this?
Aman Buzdar, MD:
I think that medicine, since it is an evolving field, because every time you answer one question and produce an answer for that question, that new research raises three new questions. So it is not something that yes, we established in the '70s, that when you give this FAC combination, that it reduces the risk of recurrence. The question was do you need to give all three drugs? Can you do it with one drug, can you do with two drugs? What is the optimal duration?
Tacey A. Rosolowski, PhD:
Well, I guess what I was actually asking was really about the controversy about aggressive treatment, you know, sort of the philosophy. Did that controversy die down or did it continue?
Aman Buzdar, MD:
Actually, the controversy, it went to the other extreme. The approach at that time was that if you pushed these drugs more and more, at higher and higher doses, you may be able to cure more and more patients. That's how, in breast cancer, the bone marrow transplant and high dose chemotherapy, in those eras a few years later, became almost like a cult culture -- that everybody-- because you could do it. And there was some successes in other diseases, not in breast cancer.
Tacey A. Rosolowski, PhD:
Kind of like an analogy of the radical mastectomy; cut away more and more and more, and you'll get rid of it.
Aman Buzdar, MD:
Yes. So, the thing is, then it became almost next to impossible to do a controlled trial, to establish whether very high dose therapy with bone marrow transplant, will result in an improved outcome or not. Everybody thought it's going to result in an improved outcome. We even at MD Anderson --Hortobagyi tried to do a randomized trial, which took a very long time, and we were able to accrue a very small number of patients. We couldn't finish the clinical trial because everybody wanted to get the treatment, because everybody's mind was made up that it is the best way to do it. But, if you move the clock farther, quickly, it became very clear, once the dust settled, that you were not able to increase the response rate. You did not keep patients alive longer, free of cancer. Actually, you unfortunately caused a small number of deaths from the treatment led complications, in that short period of time.
Tacey A. Rosolowski, PhD:
Wow. Well, I mean it's just interesting, how people respond and get on a bandwagon, you know, and as you said, almost a cult kind of mentality. There are trends in science.
Aman Buzdar, MD:
Oh yeah, because this used to be a trend. It was a challenge, because at that time, I was also chair of the IRB. Everybody will say, Oh, MD Anderson is doing it, and we will get requests that they wanted to look at our IRB minutes.
Tacey A. Rosolowski, PhD:
Oh really?
Aman Buzdar, MD:
And we had to say that those IRB minutes are not there for public consumption, because those are privileged information.
Tacey A. Rosolowski, PhD:
So, they wanted to look at the IRB. What information did they hope to gain from the minutes?
Aman Buzdar, MD:
That it is being done even at MD Anderson, things like that.
Tacey A. Rosolowski, PhD:
I see. Okay, so they wanted, in a sense confirmation to go ahead and do it.
Aman Buzdar, MD:
Confirmation, yeah.
Tacey A. Rosolowski, PhD:
Okay, interesting, all right. Well, do you want to go back to talking about the evolution of your research, after the fact?
Aman Buzdar, MD:
Yeah, I think the key thing, that became the standard. Subsequently, when the taxanes became available, we were the first institution actually, we incorporated the taxanes with the FAC combination, and it further reduced the risk of recurrence and improved outcome. There was a number of other drugs, but our drug was the smaller drug, but it was first published, which showed that adding taxane into the FAC combination, can further reduce the risk of recurrence and keep more patients alive, free of disease.
Tacey A. Rosolowski, PhD:
Wow.
Aman Buzdar, MD:
And all these studies were carried out. I was the principal investigator for all these studies at MD Anderson, and became subsequently, the larger studies confirming those things. Those are even standard today.
Tacey A. Rosolowski, PhD:
Wow.
Aman Buzdar, MD:
Anthracyclines are the backbone. If you add taxanes to that, it further reduces. That is today's standard treatment and these were -- all the work was done here at MD Anderson. "ƒ
Recommended Citation
Buzdar, Aman U. MD and Rosolowski, Tacey A. PhD, "Chapter 04: A Philosophy of Clinical Research (and Its Early Controversies)" (2017). Interview Chapters. 565.
https://openworks.mdanderson.org/mchv_interviewchapters/565
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