Chapter 02: Clinical Research in MD Anderson Culture; The Radiation Therapy Oncology Group; and Specific Clinical Trials
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Description
In this segment, Dr. Cox talks about his focus on clinical research. He begins by explaining why clinical research has been less appreciated at MD Anderson than laboratory or translational research. (As an instance of how clinical research can transform a field, he cites studies comparing the effectiveness radiation therapy vs. chemotherapy plus radiation.) Most clinical studies of radiation therapies were started by the Radiation Therapy Oncology Group (RTOG), and MD Anderson faculty was an important participant in these studies. Dr. Cox sketches the history of the RTOG, explaining its central role in organizing studies and gathering research statistics for twenty institutions. Dr. Cox explains that he viewed the RTOG as his laboratory, during his years of administrative service, and he served as senior investigator, though others were more hands-on participants.
Dr. Cox reflects on his skills in research design, offering as an example these skills, ideas he summarized in “Design and Implementation of Ion Beam Therapy,” a chapter in the book, Ion Beam Therapy: Fundamental Technology, Clinical Applications (Springer, 2011). He explains what is meant by good research design and lists several factors that contribute to a successful clinical trial.
Dr. Cox then compares laboratory to clinical studies and notes that, in general, laboratory researchers are more directive in trials, while clinical researchers tend to be more cooperative. He says that there is a give and take in clinical research that would not be comfortable for most senior laboratory investigators
Identifier
CoxJ_01_20130103_C02
Publication Date
1-3-2013
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher; The Researcher; The Clinician; MD Anderson Culture; Controversy; Research, Care, and Education in Transition; MD Anderson History; MD Anderson History; Institutional Politics; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Critical Perspectives on MD Anderson; Professional Practice; The Professional at Work; On Research and Researchers; Research, Care, and Education
Creative Commons 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
Tacey Ann Rosolowski, PhD:
In your former interview with Lesley Brunet you talked about selecting your specialty and coming to MD Anderson, so I did not necessarily want to cover those details unless there was something that you felt I needed to have in my mind before we go further?
James D. Cox, MD:
I don’t think so. I mean—I probably covered it well at that—or adequately at that time.
Tacey Ann Rosolowski, PhD:
Okay. I wanted to talk about—one thing you did not talk about during that period was really your own research program. So is that one of the research dimensions or one of the professional dimensions that you mentioned earlier?
James D. Cox, MD:
Well—yes.
Tacey Ann Rosolowski, PhD:
So maybe we could talk a bit about that.
James D. Cox, MD:
My work in clinical research which is generally much less appreciated in an environment like this than laboratory research or translational research that uses the laboratory even for clinical benefit. And then people think—well—designing and getting people to participate in and analyzing clinical trials is really pretty pedestrian stuff, but I don’t think it is.
Tacey Ann Rosolowski, PhD:
Why is there that assumption about clinical research?
James D. Cox, MD:
Well—it is just there. I mean—if you ask a lot of people in the laboratory—if you ask Josh Fidler [Oral History Interview], if you ask Margaret Kripke [Oral History Interview] coming from two very different directions, they would not pay the same degree of respect to clinical research that they would to the laboratory studies. Even though clinical research is what determines the care of patients far more immediately than what is going on in the laboratory. And when you have a clinical trial that is published in the New England Journal of Medicine or JAMA or in Lancet or—it is usually in one of those journals—it can truly change the practice of medicine or change the research environment for future studies, and if it does either of those or both I think it is pretty profound stuff.
Tacey Ann Rosolowski, PhD:
Can you give me an example of—?
James D. Cox, MD:
Well, an example comes to mind that is pretty fundamental, but it evolved over a considerable period of time, and that is the combination of chemotherapy and radiation therapy together relative to radiation therapy alone. And in virtually every site that was studied, the combination of cytotoxic drugs now—I do not mean hormones, but cytotoxic drugs—that is true in hormones too—but cytotoxic drugs and radiation therapy prove to be superior to radiation therapy alone in survival. I mean—not just in control of the tumor or some other earlier or secondary end point, and this is true in cancer of the esophagus, cancer of the lung, tumors in the head and neck, cancer of the cervix. And in other sites like cancer of the larynx and cancer of the anal canal it had a big difference in avoiding the surgical procedure that would lead to major morbidity like laryngectomy or abdominoperineal resection resulting in a colostomy. So in each of those it proved to be superior, and each of those trials was not easy to mount. And there was resistance—there were pockets of resistance here at MD Anderson to participating in those trials. At that time, or during much of that period of time outside of MD Anderson, I was chairing the Radiation Therapy Oncology Group, and most of those trials were either started and subsequently published where the RTOG was the major participating group, and that is natural because it was the only group that was asking radiation therapy related questions by and large. Now there were a few exceptions but—
Tacey Ann Rosolowski, PhD:
Can I ask you—I mean—just to interrupt to get a sense of how this worked. So these trials were founded through the Radiation Therapy Oncology Group, which was the organizing body for them—was that the idea? And then there were you and others from MD Anderson who participated? I am just trying to get a sense of how the RTOG (both speaking at once).
James D. Cox, MD:
The RTOG has been in existence since the late 1960s. And it was the organizing group—it also managed the statistical center and the operations for about 20 institutions that contributed large numbers of patients. And they were mostly academic institutions—major academic institutions, but not all of the major academic. They included—for example—the University of California San Francisco—UCSF. They included Washington University in St. Louis, Thomas Jefferson in Philadelphia, eventually—although not at the very beginning—the University of Pennsylvania, and they included NYU. And only after I came to MD Anderson did MD Anderson join.
Tacey Ann Rosolowski, PhD:
Why? Why was that delay in place?
James D. Cox, MD:
Well I think the previous leadership in MD Anderson was interested in—Lester Peters—was interested in laboratory research. I think he felt whatever clinical research were to—clinical research that should be done should be done at MD Anderson, and then if somebody else picked it up and wanted to do it on a national basis, that was for them to do. But the RTOG had these 20 more or less core institutions, and then they had another 150-200 institutions scattered throughout the United States and Canada that participated. So they were able to recruit large numbers of patients, and I kind of—during that period of time—I kind of viewed that as my laboratory. So I was sort of the senior investigator for most of those trials but more as a facilitator helping other people to succeed. The vast majority of the trials that were published from that period, my name was not there as the senior author. So it turned out to be a very worthwhile thing, but in terms of academic recognition—you know—ten or fifteen years later who would know? They might know—oh yeah Jim Cox chaired the RTOG for a decade, but—you know—what does he have to show for it? And there were a few trials that I participated very heavily in.
Tacey Ann Rosolowski, PhD:
And these were also trials that were combining chemotherapy with radiation?
James D. Cox, MD:
Many of them. Many of them.
Tacey Ann Rosolowski, PhD:
I read as I was doing background research for this interview that you said that you have a particular strength in putting together research studies—somehow an investigational method, and I wondered if you could talk a little bit more about what you meant by that? What is a good research design, and where does the science stop and art begin?
James D. Cox, MD:
It is interesting—I published a book chapter for a different purpose. The title of it kind of goes to the question that you are asking. This is in a book called Ion Beam Therapy—so it is relatively recent. But the title of the chapter is Design and Implementation of Clinical Trials of Ion Beam Therapy, and it goes through what are the critical elements. Among them are having hypotheses that not only I feel are worth testing, but that the community of participating physicians has come to the conclusion—or perhaps I have helped them come to the conclusion—that these are questions that are worth answering because to do an effective clinical trial you have to have a good question. You have to have a group of investigators interested enough in that question to contribute their patients to the study because it takes extra time and effort always to ask patients to participate in clinical trials. Now that takes extra expense usually. And then oftentimes there is some countervailing view of what should be done and the details of radiation therapy such as fractionation, the details of the chemotherapy in terms of what drugs and what doses, and there are a lot of details in there that have to be worked out usually needing other people as leader to help move that forward. It is the sort of thing that I cannot tell them what to do; they have to be motivated to say, “Yes, this is worth doing.” It would totally fail in the Congress of the United States. Anyhow—and then you have—and those questions are not answered quickly. Usually a trial ideally would answer this question within three years, but they rarely do. And some may take five years or even ten years. And it is still a worthwhile trial unless some other hypotheses come forward that are so much more compelling that they want to drop doing that study. Usually the study is worth completing. And so you need those elements, and I have outlined them in that chapter.
Tacey Ann Rosolowski, PhD:
Are those elements—to what degree are those elements different from the good design elements of laboratory research? And I am—is there—in those differences—is there something about those differences that helps contribute to the prejudice against clinical research?
James D. Cox, MD:
I think in laboratory studies the director of the laboratory is much more directive. He or she much more likely tells the people in the laboratory what to do. Occasionally there will be a colleague that is sort of working on something that might be adjacent or maybe complementary in the same general laboratory, but usually it is post-doctoral fellows, graduate students, people who the director of the laboratory is directing. And that is different from what happens in cooperative groups.
Tacey Ann Rosolowski, PhD:
Among whom are peers—right?
James D. Cox, MD:
Really are peers each with their own constituency, each with their own body of patients, and where it is much more collaborative science than what goes on in the laboratory. And maybe the fact that it is collaborative science is one of the things that is looked down on.
Tacey Ann Rosolowski, PhD:
Yeah it doesn’t—it kind of doesn’t fit the mold of the lone researcher—
James D. Cox, MD:
Right.
Tacey Ann Rosolowski, PhD:
—pushing back the frontiers.
James D. Cox, MD:
That is right.
Tacey Ann Rosolowski, PhD:
Yeah.
James D. Cox, MD:
That is right. And there may be many other reasons. But one of the other reasons is that it is usually done by clinicians. And there are the clinicians and there are the laboratory scientists, and laboratory scientists always wish that they were making as much money as the clinicians, but they would not want to give up the fact that what they are doing is autonomous or at least semi-autonomous and much more at the forefront.
Tacey Ann Rosolowski, PhD:
This may be an unfair question, but do you see that there are kind of different personalities attracted to laboratory versus clinical research? I mean—or is that too general of a statement to make?
James D. Cox, MD:
I think in general that is true. There is a give and take in clinical research that would not be comfortable to most senior laboratory investigators. So I—yeah—I think there is a difference.
Recommended Citation
Cox, James D. MD and Rosolowski, Tacey A. PhD, "Chapter 02: Clinical Research in MD Anderson Culture; The Radiation Therapy Oncology Group; and Specific Clinical Trials" (2013). Interview Chapters. 784.
https://openworks.mdanderson.org/mchv_interviewchapters/784
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