Q&A with Dr. Carl Elliott: Making patient protection a priority for clinical trials

Dr. Carl Elliott is a brave man. A bioethicist with an MD, Elliott took on powerful interests at his own university on behalf of a woman he barely knew and a patient he could not save. The patient was Dan Markingson, a 26-year-old University of Michigan graduate from St. Paul. He struggled with mental illness beginning in 2003, and he eventually began hallucinating that he was being ordered by Satanic forces to kill.

His psychiatrist, Dr. Stephen Olson, works where Elliott works, at the University of Minnesota. Olson had Markingson involuntarily committed and later enrolled him in a drug study intended to find out whether AstraZeneca's anti-psychotic drug Seroquel was superior to its competitors. Markingson's mental health spiraled downward, and he ended up committing suicide in a brutal way. The story was first broken by Jeremy Olson and Paul Tosto of the St. Paul Pioneer Press.

Elliott has written numerous articles forThe Atlantic Monthly, The New Yorker, The American Prospect and other outlets and multiple books, including the recent White Coat, Black Hat: Adventures on the Dark Side of Medicine. He thought there was a deeper story to be told: a story about why no one in his university's power structure seemed to care.

I reached him at his office at the Center for Bioethics at the University of Minnesota. The interview has been edited for space and clarity. The first part of our interview appears below. The second part will be posted next week.

Q: The Dan Markingson case had been written about before you started reporting on the case. What made you decide that there was a story that had not been written?

A: I knew one of the reporters, Paul Tosto, who sent the story to me while I was on sabbatical in South Africa. I was working on a piece for the New Yorker. I couldn't read it very carefully while I was there because I was trying to chase down a story about this sociopathic psychiatrist. When I finally did read it, it wasn't really a matter of deciding that there was something more to write. It was more that this story had happened at my own institution and no one seemed to be doing anything about it. And so, at first, I just wanted to look into it to see if the facts were as they were reported. I wanted to know whether or not Mary Weiss, Dan's mother, was credible. When I started asking around here, I was just assured by everyone I talked to that I shouldn't believe that anything bad had happened. "It's all distorted and all untrue. There's much more to it." It was sort of hinted to me that the real blame for the suicide lay somewhere else entirely.  At that point I wasn't thinking about writing anything. I just wanted to understand what had happened. I've been writing about clinical trials and research ethics for years, and I was always pointing the finger at corporate interests. Here something scandalous seemed to be happening at my own institution, and I thought I needed to look into it.

Q: What did you find?

A: What I found is that hardly anyone had read the Pioneer Press series. Not a single person in the bioethics center where I work had seen it. The people who had seen it were in psychiatry and in the administration. So I started distributing it. I started using the series in my classes, and that was not met with a lot of enthusiasm by administrators. And I just wanted to know more about it. So I called Paul and said, "What is the story about Mary Weiss? Is she credible?" He said, "Yes, you should meet her." She was immediately suspicious of me because I work at the University of Minnesota. But she agreed to meet with me. I found her totally credible, reasonable and very smart.

Q: If she was suspicious of you at first, how did you get her to open up?

A: The fact that I was a friend of Paul Tosto probably helped. What was so horrible about it was that not a single person from the university had come to her and said, "We're sorry." Her son killed himself in a clinical trial at the university, and you think at least some sort of human contact would have been warranted. But she had heard nothing from anyone.

Q: Maybe in some ways you were the first official person from the university to connect with her?

A: Maybe. I have no idea what made her trust me. It was probably desperation more than anything else. By the time I got in touch with her, she and her friend Mike Howard had been sending out complaints to any possible agency that they could imagine would help. I got in touch with her in fall of 2008. It had been four years since Dan had killed himself, and she had been through an unsuccessful lawsuit. She had complained to the FDA, and the FDA report was a whitewash. She went to the medical board, and they didn't do anything. She had been complaining from the start to the university. She didn't want him to be enrolled in the trial, and she didn't want him to be discharged from the hospital. If you look at the correspondence, you can hardly imagine her doing anything more to try to help her son, and she was just totally ignored. I think now she's a lot better informed and savvier about who to get in touch with. For example, when she was trying to get Dan out of the trial, I doubt she knew that she could have gone to the IRB (institutional review board). She probably didn't know what an IRB was.

Q: Where did you first pick up the paper trail in this case?

A: When I first met with Mary, I wasn't interested in writing about this. I just wanted to find out what had happened and figure out for myself whether things were as bad as they appeared to be. Once I did decide I was going to write about it, it all started with her. Because she had made so many of these complaints, she and Mike Howard had access to a huge amount of material that they were able to give me without a lot of digging. All of the medical records and court records came out of that. She put me in touch with her lawyer, who gave me free rein over the depositions and everything there.

Q: What first struck you about the records?

A: Not only did it look as if everything that had been reported in the Pioneer Press was true, it looked like it was even worse than had been reported. The problem, then, is what do you do about it? To be honest, I knew it was not going to be a happy time for me here at the University of Minnesota if I were to write about it. But I couldn't see any other way. I don't know how much you know about the history of conflict of interest at the University of Minnesota, but there have been some significant problems for many years. The response of the university has been the same every time: "We have done nothing wrong. We see nothing wrong. We value our ties with industry, and we stand behind our researchers." Even when the U.S. Senate Finance Committee was investigating the chair of spine surgery with $1.2 million in undisclosed income form Medtronic, the university saw no problem with that.

It soon became clear to me that the university wasn't going to do anything at all about Dan's death. I couldn'tget anyone to admit that there was even enough to make this case worth looking into much less admit that something went wrong. Their position was: "This was so obviously a misguided accusation that we don't even need to look into it. Just look at the summary judgment where the case was dismissed in court." The sponsor of the trial at the time was being sued and had agreed to pay half a billion to settle this federal investigation for fraudulent marketing. So the more I started to look into that. the more it became clear that some of those manipulated trials were leading back to the University of Minnesota as well, in particular to Charles Schulz, one of the co-investigators on the CAFE Study. It looked to me that while the Pioneer Press story had been accurate, it didn't get at this larger issue of how pharmaceutical companies use clinical trials as marketing tools and how dangerous that can be.

Q: Did the paper trail take you in any unexpected directions?

A: There was one thing I was stunned by. Looking over the depositions of the people in charge of research (subjects) protection here, I could not believe some of the things they said. My feeling about the case when I was going in was that the main problem with the study must have come from the investigators themselves, meaning Olson and Schulz. And AstraZeneca had to have been at fault, I thought.

But then I started reading over the depositions of Moira Keane, the head of the IRB here, and her boss, Richard, who is in charge of all human subject protections, or at least was then. There was this long question and answer session between the lawyer and Moira Keane whether it was the IRB's responsibility to protect subjects in clinical trials. If you asked any person associated with an IRB in America what the function of an IRB would be they would tell you it's to protect subjects of clinical trials. It will say that on websites of IRBs, but when Gale Pearson was deposing Moira Keane, she kept insisting it wasn't the responsibility of the IRB to protect subjects.

Gale was so stunned by that answer that she kept going back to it again and again. And Moira Keane kept saying yes. When Gale questioned Richard Bianco, he agreed with that and said exactly the same thing. Why would someone say that under oath? That is so obviously wrong. I couldn't quite understand it. Were they being coached to say this? If you genuinely believe that, then why does the IRB even exist?

Q: Did you talk to them about those answers?

A: I was on the IRB here for a number of years, and so I emailed Moira and said, "Do you really believe this?" The first answer I got was,"I can't talk about any of this." That was often the answer I got at the University of Minnesota. They would say, "Can't talk. Subject of litigation." Which it was not. In fact, the University of Minnesota had filed legal action against Mary Weiss to insure there would be no litigation. But I asked in an email about it and said that she seemed to be saying in the deposition that it's not the job of the IRB to protect subjects. And she said, "That's true." There was this convoluted reasoning that it's the IRB's job to make sure that the investigator has a plan to protect subjects or something like this. That the IRB did not have a direct responsibility to protect subjects.

Q: How did you respond?

A: I said that it's the investigators and the sponsor that the IRB is supposed to be protecting subjects from. Who do you think is putting them in danger if it's not the people conducting the study?

Q: What was the answer?

A: I got no response to that.

Next: Putting patient safety back into clinical trials

Email me at askantidote@gmail.com and follow me on Twitter: www.twitter.com/wheisel.

See all the posts in "The Markingson Files" series.

Related Posts:

Q&A with Dr. Carl Elliott, Part 2: Finding fault with his own university after patient's death

The Markingson Files: University can't control the story of a clinical trial suicide