Chapter 06: An Interest in Clinical Trials, Design of Research, and Government Oversight
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Description
In this segment, Dr. Levin explains how his interest in clinical trials evolved, as well as his understanding of the issues involved in running such trials. He describes a trial run with a drug provided by a philanthropist who had imported the drug from Russia. He received a call from the NCI, who informed him they were taking over the trial. He quickly learned that clinical oncology trials have to be carefully monitored for safety. He briefly describes trials and collaborations he undertook to study liver cancer. In this segment, Dr. Levin talks about the design of clinical trials.
Identifier
LevinB_01_20130207_C06
Publication Date
2-7-2013
City
Houston, Texas
Interview Session
Bernard Levin, MD, Oral History Interview, February 07, 2013
Topics Covered
The Interview Subject's Story - The Researcher The Researcher Professional Practice The Professional at Work Multi-disciplinary Approaches On Research and Researchers E: Ethics Obstacles, Challenges Controversies
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:
So it was multidisciplinary care and then also design of clinical trials?
Bernard Levin, MD:
Right. I started to develop an interest in doing clinical trials and was rather foolish, because I didn’t really appreciate all the issues involved. I remember with horror in retrospect one attempt to do a clinical trial on a relatively new drug that was provided to us through a philanthropist of a sort. It was a man who had made a large amount of money, and he had a contact at the University of Chicago who approached me and said that this man was willing to import a drug from Russia that might be more effective against colon cancer. And we did some initial clinical trials with this drug. But really, I was not equipped for all the issues involved. And at that time the University of Chicago probably wasn’t well equipped to do clinical trials.
Tacey Ann Rosolowski, PhD:
And when you say the issues involved, what are you referring to?
Bernard Levin, MD:
Safety, purity, drug dosage. There were a lot of issues. Subsequently, I received a rather anguished call from the National Cancer Institute who asked me what I was doing and subsequently said they would be taking over the responsibility of this. I think they probably saved my hide in the process, because I think we were foolhardy at the time.
Tacey Ann Rosolowski, PhD:
So many people have spoken about this period of the early 70s. One person called it the Wild West, that there was a lack of controls. People were kind of figuring out how to conduct this kind of research.
Bernard Levin, MD:
I was as guilty or a victim as much as anyone else. And I suspect people—patients—suffered and some may have benefitted. But it was certainly—there was little in the way of informed supervision. I wish I had had more of that at the time, which would have been more appropriate.
Tacey Ann Rosolowski, PhD:
So when the NCI said they would take over, did that mean you were going to be supervised by them or that they were taking over the entire project?
Bernard Levin, MD:
They were taking over the project, or they made it so difficult that it was not appropriate for me to continue. I think I was relieved.
Tacey Ann Rosolowski, PhD:
So what did you learn from that experience?
Bernard Levin, MD:
I learned that the field of clinical oncology trials is one that has to be governed by very strict criteria as to safety and outcome. Now around this time, I and other colleagues became aware of a technique to treat patients with liver cancer—metastatic colon cancer to the liver. And that took the form of an implantable pump that was put in surgically and was placed under the skin, and that led to a catheter leading to the liver. And it was an ingenious device developed primarily by Bill Ensminger—who is still a cancer treatment pharmacologist at the University of Michigan—and a company that he worked with. So I interested a surgeon who is a friend, Richard Karl—who subsequently became the director of the Moffitt Cancer Center in Tampa—to develop this further. And we went to Michigan and learned how to implant the pump, fill it, use the drugs that were involved, and started doing this work at the University of Chicago.
Tacey Ann Rosolowski, PhD:
What was the drug?
Bernard Levin, MD:
The drug was 5-flourouracil—actually FUDR, floxuridine. And it was placed into a little pump container through the skin, so you could access the pump by feeling for a little dimple in the pump, sticking a needle into it, filling it, then checking that it was in the right place. Then through a very ingenious mechanism this would slowly leak into the liver—the artery leading to the liver—and then profuse the liver. That’s the theory. Of course, there were many tricks and many problems with this device. But some people believed in it and thought this was going to solve the problem of liver cancer. Unfortunately, that turned out not to be quite the case, although, in some instances, it was very dramatically effective. But this lead to an entirely new collaboration between nursing, between surgery, radiology too. My wife became involved in reading the scans of patients who were treated. And by then, Richard had identified the fact that he was going to be leaving and going to Tampa. I was starting to think about the possibility of moving to Houston. I applied for a research grant—an RO1—to study this. It was called an inter-institutional RO1. A number of centers would get together and pool their results, and we worked very hard to pull this all together. At about that time, my move to MD Anderson had become more definite. And Richard had already left. There was some question as to how effective this pump really was, but it was being used widely, particularly at Memorial Sloan-Kettering. One of the researchers there had developed a major program in that.
Tacey Ann Rosolowski, PhD:
Can I ask what year are we talking about here?
Bernard Levin, MD:
This is about ’82 by now—’81 or ’82.
Tacey Ann Rosolowski, PhD:
So you said there were questions about just how effective this pump was.
Bernard Levin, MD:
Right, and how safe it was, because the drugs also could cause substantial damage to the arteries and to the liver itself if you didn’t do it right, if you got the dosage wrong. So it had become quite a major area of interest.
Tacey Ann Rosolowski, PhD:
Can I ask you—one of the things I was thinking about as I was looking over the types of investigations you’ve taken part in is that many of them take place over a long period of time. It takes a while to figure out how effective—are there particular challenges with the design of clinical studies? Or what are the challenges of clinical studies that have to transpire over a long period of time? There may be a variety of interventions. How did you learn how to finesse those kinds of questions?
Bernard Levin, MD:
That’s an important question. First of all, many of the studies I was involved in were collaborative. So other people were involved and often doing much of the work, so I could be there along for the ride so to speak. They were the ones who carried the brunt of the work. A number of the clinical trials were slow accruing or were only confined to certain categories of patients. So that limited the accession rate. Particularly before building a reputation it was hard to find patients for certain trials, although colon cancer is fairly ubiquitous, and that wasn’t as difficult. But there were some other trials—pancreas cancer, for example, that it took longer, because those people tended to die more quickly, unfortunately. There was also a period during that phase where I was involved with the National Pancreas Cancer Project in New Orleans. And I took part in that similar to the National Large Bowel Cancer Project. At one time I had been approached about becoming the leader of that and moving to New Orleans. That was also in the early 80s. Again, that had its own ramifications. But I’ll never forget going to Louisiana State University and seeing the separate doors for entry, whites and blacks. They were still there. Probably not much in use anymore but the feeling—this was back to an older era in my life. And New Orleans at that point just didn’t fill me with real scientific vigor. It just seemed like a relatively backward place, especially the LSU. It may not have been, but that was my impression, at least in the field I was interested in.
Tacey Ann Rosolowski, PhD:
So in ‘82, you were thinking about coming to Houston?
Recommended Citation
Levin, Bernard MD and Rosolowski, Tacey A. PhD, "Chapter 06: An Interest in Clinical Trials, Design of Research, and Government Oversight" (2013). Interview Chapters. 1342.
https://openworks.mdanderson.org/mchv_interviewchapters/1342
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