INVESTIGATORS: U of M drug study criticism grows

A man who was recruited for a clinical trial at the University of Minnesota says he was misled about the possible dangers of the drug study and suffered horribly because of it. Now, a former governor is joining the call for an outside investigation of the university's human research programs.


Dec. 5, 2013: U of M Senate resolves to review human research

Nov. 17, 2013: Side-effects of drug study?

"I said, 'I'm done. I'm not taking this anymore,' because I thought I was going to die," Robert, who asked that his last name be withheld, told the Fox 9 Investigators.

All he wants is an apology.

"What happened to me was really horrible," Robert reflected.

However, a former government regulator believes what happened to Robert is so disturbing it warrants a federal investigation.

"That whole picture is very troubling and reflects a failure to ensure that subjects are being adequately protected regarding this research," Dr. Mike Carome said.

Robert's story is part of an ongoing Fox 9 Investigation into drug research conducted by the University of Minnesota's Department of Psychiatry.

Last fall, the Fox 9 Investigators reported on the case of Dan Markingson, who died after trying to cut his head off while enrolled in a drug trial. Robert says his experience in a different study nearly drove him to commit suicide.

"They don't care about what happens to the person," he said. "They care about the money from the drug company."

Back in 2007, Robert developed ringing in his ears, started hearing voices and was feeling anxious. He feared it was a brain tumor and went to the emergency room. He was transferred to the psych unit at Fairview Riverside Hospital, which is where he was diagnosed with paranoid schizophrenia. That's where he was approached by U of M researchers.

"Immediately, they were on me to do experimental medications, non-FDA approved -- and I had never been on medications in my life," Robert said.

Robert said he felt coerced to enroll in a trial for an experimental drug called Bifeprunox.

"Then, they say you have a giant medical bill and if you do the research, you won't have this giant medical bill," Robert recalled.

Robert admitted he was worried about the safety of Bifeprunox since it did not have FDA approval.

"They told me the drug was safe," he said. "He told me it was going to be the next treatment for schizophrenia and everybody was going to be taking it."

Robert gave the U permission to release his medical files to the Fox 9 Investigators. Dr. Stephen Olson was in charge of the trial, and part of his salary was paid by the drug's maker, Solvay Pharmaceuticals.

Olson wrote in the clinical record that Robert was "very interested" in the opportunity to have his medical expenses covered by the study because of a lack of insurance. He also noted that Robert did have concerns about the drug's safety, writing "although initially leery of the Bifeprunox study as was experimental mediation, he was reassured that enough patients have been treated to be more sure of its safety."

"That is inappropriate," Carome said. "It minimizes the risk and that was the very reason this trial was being done -- to try and find out if the drug is safe."

Carome is a physician who previously worked for the federal government's Office of Human Research Protection. He helped develop and write the regulations that are supposed to guard research subjects from abuse. Now, he's on staff with the watchdog group Public Citizen.

"One should not have provided any assurances that the drug is safe," Carome said.

The Fox 9 Investigators asked Carome to review Robert's records.

"It is understating the risks," Carome said.

In hindsight, it's now known that there were significant risks associated with the drug. Just weeks after Robert enrolled in the study, the FDA rejected Bifeprunox for approval. Within months, the Solvay Pharmaceuticals halted all research after the medication was linked to the death of a study subject in Europe who suffered liver failure.

"I was incompetent and I didn't know what I was doing," Robert said.

Robert can't recall if university researchers ever told him about those developments. There was no written notification the Fox 9 Investigators could find in his file about the FDA denying approval of the drug.

Robert did sign a consent form when he first enrolled in the study, and there was a line in it about a death in another Bifeprunox study related to liver abnormality.

"The way the language read on the consent form downplayed that risk inappropriately," Carome said.

Records show that while Robert was in the trial, he complained of having abdominal pain.

"I should have been taken out of the study right away when I had these pains," he said.

Robert went to the emergency room three times -- once by ambulance. One ER doctor suspected the pain might be related to the experimental drug. In fact, abdominal discomfort and constipation were listed as possible side effects of Bifeprunox.

Olson, the study investigator, made note of Robert's complaints and reported them to the drug company, but documents show he listed their connection to Bifeprunox as "unlikely."

"The presumption should have been that those were due to the drug unless proven otherwise," Carome said.

Three months into the study, Robert said the pain was so bad that he was having thoughts of suicide and decided to drop out of the research. Here's what Olson wrote about that: "He decided to quit the study due to these psychosomatic Sx [side effects]."

Carome finds it troubling that Olson discounted the possibility that the drug was responsible for Robert's symptoms.

"That's not really in the best interest of the human subjects whereas it might be in the best interest of the sponsor who hopes someday to get this drug approved by the FDA," he explained.

Olson declined to be interviewed by the Fox 9 Investigators. He has not responded to questions about what he told Robert early on about the drug's safety or why he determined the side effects Robert was having were psychosomatic.

In a statement to Fox 9, Olson called into question Robert's ability to recall what really happened in 2007.

"His medical record shows extreme anxiety and paranoia, a history of head injuries and lengthy battle with alcoholism," the statement read in part. "It is highly inappropriate for him to be put in the media spotlight as a spokesperson for clinical trial safety."

After Robert left the study, he sought conventional treatment for his illness and is doing well.

"People are more important than research, and they don't seem to understand that," he said.

His vulnerability at the time of his recruitment is exactly what concerns experts like Carome and others.

This month marks the 10th anniversary of the suicide of Dan Markingson, a research subject in another drug trial run by Olson. Markingson's family accuses university researchers of coercing him to enroll in the study and then ignoring their pleas to have him removed because they feared he was in danger of killing himself or someone else.

An FDA investigation cleared the U of any wrongdoing, but a group of 170 scholars worldwide want the case to be reopened and to have the U's human research practices scrutinized by independent experts.

"My concern is there's widespread abuse of psych research trials -- that this isn't an isolated case, that there are more deaths like this," ?said? protestor Eden Almasude.

Some medical students at the U want an outside investigation as well. They recently staged a protest at the board of regents meeting.

"I want to see some justice done on this," former Minnesota Governor Arne Carlson said.

Carlson contacted the Fox 9 Investigators after seeing the coverage of the research controversy.

"I'm going to continue to press," he vowed.

He has written letters to the university's president, the board of regents, and Gov. Mark Dayton, urging them to do something.

"I can't get a solid answer on how many people, how many have been victimized by this," Carlson said. "What does that tell us? It tells us that secrecy runs rampant at a time when we need openness."

Carlson says nothing short of an independent, very public review of what is going on inside the university's psych research department will do.

The U declined a requests for interviews about the Markingson case or Robert's. They say an internal investigation of Robert's complaints is currently underway.

"I told my therapy group this is like some horror story out of the 1950s," Roberts said. "I couldn't believe it happened in this present day."