Who’s Delusional? A University Doc & A Clinical Trial
9 CommentsBy Ed Silverman // May 19th, 2008 // 6:52 am
Dan Markingson, known as Subject 13 in a clinical trial at the University of Minnesota, killed himself four years ago. A university official described his death as “tragic” and a “serious adverise event” in a memo to the FDA, while noting that suicide was, “unfortunately, not uncommon in this study population.” But not unpredictable, The St. Paul Pioneer-Press writes.
His mother later filed a lawsuit, accusing Markingson’s psychiatrist and the study’s director, Stephen Olson, of coercing him to sign up. The lawsuit also claimed the university kept Markingson enrolled to preserve its research and to keep payments coming for his participation, according to the paper. The study, which was funded by AstraZeneca and spread among 26 institutions, compared the effectiveness of three antipsychotics - Seroquel, Zyprexa and Risperdal.
Full participation required Markingson, who received AstraZeneca’s Seroquel, to take one antipsychotic for up to a year and to appear for checkups. As Subject 13, he was worth $15,000 to the university, with some going to Olson’s salary and the psychiatry department. Switching or adding meds could have disqualified Markingson and halted payments. Overall, the study offered $327,000 and an opportunity to raise the profile of its schizophrenia program, the paper writes, adding that the lawsuit claimed the money caused a conflict of interest for Olson.
The death prompted reviews by the state mental health ombudsman and the FDA about the conduct of the university and Olson, who was Markingson’s only psychiatrist at the time he recruited him into the study. The reviews and the lawsuit probed whether Markingson was coerced into the study by the threat of commitment to a psychiatric hospital and whether the university provides adequate protection of mentally ill research subjects.
The lawsuit also revealed the pressure to recruit research subjects. Neither Olson nor the university was blamed by any oversight agency for the death, or cited for research violations. In fact, the university was dismissed from the lawsuit in February, and Olson settled in April.
In a recent interview, Olson told the paper that it is difficult for an academic physician to avoid this conflict and that in this case the conflict didn’t matter. As Olson’s patient, Markingson was going to receive one of the three anti-psychotic drugs being tested in the study anyway. As a study participant, Olson maintained, Markingson would receive more attention and monitoring.
Olson also said in his deposition that participation in the study was never linked to the commitment decision. Markingson could have selected standard treatment or backed out of the study, Olson said.
But Markingson’s mom doesn’t believe her son understood he could have those options. Markingson signed a consent form that said he was “not under any obligation to participate in a research project offered by your doctor.” He also signed a hospital discharge plan that warned him to follow Olson’s instructions, take his medication and show up for study appointments. “Consequences for not following this plan,” it stated, “could result in court commitment to the hospital.”
Recruiting patients for psychiatric research is a challenge, but the study presented special problems. First-episode schizophrenics aren’t easy to locate. They don’t go to clinics or support groups. Some don’t admit to an illness until they are brought to a hospital against their will, according to the paper. The study was an early opportunity for Olson to add research experience to his academic credentials and the university had recruited him in 2001 for his expertise in schizophrenia.
Exchanges between local and national study officials made it clear that there was pressure for results and a “risk” that the study would be shut down if it didn’t recruit enough patients.
Olson originally recommended that Markingson be committed, but then advised a judge to stay the commitment for six months, the Pioneer Press writes. Olson did not disclose to the court that he was Markingson’s only psychiatrist at the same time he recruited him for his drug study. Markingson’s county case manager learned of Olson’s dual roles, but after Markingson had enrolled in the study.
Two weeks before Markingson’s death, Olson recommended another six-month commitment to prevent his patient from moving back to California. Olson’s letter to the case manager stated that Markingson had “little insight” into his illness and would be at “risk” on his own of slipping back into delusional behavior. The letter didn’t mention the study, which had several months left, according to the paper.
The university’s Institutional Review Board acted as the safety watchdog of the study, but leaders of the IRB said in court depositions that they never learned about his mother’s concerns or how Markingson was recruited until after he died, the paper writes.
The state ombudsman raised concerns after Markingson’s suicide, including the method of ensuring that patients were taking their pills and the ethics of one doctor both recruiting and treating a patient. The report also questioned whether Markingson was truly eligible for the study, because he wasn’t diagnosed with schizophrenia until several weeks after he had enrolled, according to the paper.
Other problems: the paper writes that Olson waited several weeks before notifying participants of a new diabetes risk with anti-psychotic drugs. The university’s records also showed an office visit with Markingson that would have occurred after his death.
The lawsuit ended this year after a judge ruled that the university had statutory immunity from such lawsuits and that AstraZeneca shouldn’t stand trial because there was no convincing proof that its drug caused Markingson’s death. His mom settled with Olson, the only defendant left, she tells the paper that she was granted $75,000, which went entirely toward legal bills.
The study results were released in 2005 and showed little difference in effectiveness of the three drugs or the amount of unhealthy weight gain by study participants. Some observers believed AstraZeneca backed the study to prove that Seroquel caused less weight gain than the others. Buried in the results: There had been five attempted suicides, two completed suicides, the paper notes.
Researchers weren’t shocked. The lifetime suicide rate among schizophrenics is as high as 10 percent. Two deaths among 400 study participants wasn’t unexpected. University officials, meanwhile, believe their system to protect human research subjects is effective and that Markingson was a sad aberration.
“It is a tragedy” to lose a patient to suicide, Olson said. “We’re just redoubling our efforts to understand what goes on in the mind of someone whose mind isn’t working properly.” Olson is enrolling patients in studies, including another AstraZeneca drug trial called HALO, and worries that publicity of the suit will make recruiting harder.
The university, by the way, is demanding $57,000 from from Markingson’s mom to cover its legal bills.
Dan
The Human Injury of Lost Objectivity
If I were to rate the corruptive tactics performed by big pharmaceutical companies, the intentional corruption of implementing fabricated and unreliable results of clinical trials by pharmaceutical companies who manipulate these trials they sponsor because of their power to control others involved in such trials that is largely absent of regulation would be at the top of the list, and likely the most damaging to the requirement of authenticity and, more importantly, assuring the safety of the public health.
Decades ago, clinical trials were conducted at academic settings that focused on the acquisition of knowledge and the completely objective discoveries of meds. Then, in 1980, the Bayh-Dole Act was created, which allowed for such places to profit off of their discoveries that were performed for pharmaceutical companies in the past. This resulted in the creation of for-profit research trial sites, called Contract Research Organizations, which is often composed of community research sites with questionable investigators possibly void of necessary research experience or quality regarding their research purpose and ability. Since they are for- profit, with some CROs making billions of dollars a year. The trials conducted at such places are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial being conducted involving their med being studied in the trial. This coercion is done by various methods of deception in subtle and tacit methods. As a result, research in this manner has been transformed into a method of marketing, which includes altered results of the trial to favor the sponsor’s med. Their activities are absent of true or applied regulation, and therefore have the autonomy to create whatever they want to benefit what may be a collusive relationship between the site and the sponsor.
Further disturbing is that once the creation of the trials is completed, they are then written by ghostwriters often, although no one seems to know how often. These people are not identified and acknowledged by the sponsor, and may not be trained in clinical research overall, as they are simply freelance writers, as one does not need research training or certification in order to perform this function. Rarely do trial ghostwriters question their instructions about their assignment, which is clearly deceptive and undocumented, as the mystery writers are known to make about 100 grand a year. This activity removes accountability and authenticity of the possibly fabricated clinical trial even further. The corruptive act is finally completed by the sponsor hiring an author to be placed on the trial that likely had no involvement with the trial, and, along with others, was paid by the sponsor for doing this deceptive act.
To have the trial published, the sponsor pays a journal to do this, along with the promise of purchasing thousands of reprints of their study from the journal. Again, how often this process is performed is unknown, yet frequent enough to create hundreds of such false writers and research sites to support the pharmaceutical industry. So benefits of meds studied in such a malicious way potentially can harm patients and their treatment options and safety risks. The purchased reprints are distributed to the sponsor’s sales force to share the content with prescribers.
Such misconduct discussed so far impedes research and the scientific method with frightening ethical and harmful concerns. Our health care treatment with meds is now undetermined in large part with such corruptive situations, as well as the possible absence of objectivity that has been intentionally eliminated. Trust in the scientific method in this type of activity illustrated in this article is absent. More now than ever, meds are removed from the market are given black box warnings. Now I understand why this is occurring.
Transparency and disclosure needs to happen with the pharmaceutical industry for reasons such as this as well as many others, in order to correct what we have historically relied upon for conclusive proof, which is the scientific method. More importantly, research should not be conducted in a way that the sponsor can interfere in such ways described in this article, requiring independent sites with no involvement with the drug maker. And clearly, regulation has to be enforced not selectively, but in a complete fashion regarding such matters. Public awareness would be a catalyst for this to occur, after initially experiencing a state of total disbelief that such operations actually are conducted by such people, of course. We can no longer be dependent on others for our optimal health. Knowledge is power, and is also possibly a lifesaver.
“Ethics and Science need to shake hands.” ……. Richard Cabot
Dan Abshear
ol cranky
You seem to be making the assumption that clinical trials conducted at academic research centers is somehow better, more ethical and/or higher quality than the work done in non academic institutions. I can tell you for a fact that this is far from the case. In general,the KOLs at academic centers are even bigger pigs than those in private practice or at clinical research centers. Not only are these PIs often disengaged (at best), they also tend not to adhere to protocols and demand payments well in excess of FMV. In other words, gluttony abounds when it comes to physicians who are KOLs or too cozy a relationship with pharmaceutical companies.
Mary Weiss, mother of Dan
Thank you for posting information from the articles that appeared in the St. Paul Pioneer Press May 18, 19 & 20 regarding the death of my son, Dan Markingson. I would like to add one important item, however, that comes from an entry in Dan’s hospital file the second day in the hospital, Nov. 13, 2003. I do not believe the reporters had access to Dan’s hospital file. I, of course, did not either until after Dan’s death. Dr. Olson wrote on Nov 13:
“However, his grandiosity, the recent sleep disturbance, and somehwhat increased self-esteem even present now also raise the question of bipolar disorder. If in fact he is really better now and not just concealing the full extent of his delusional thinking, the rapid response to a single dose of Ativan would lean in favor of bipolar disorder.”
There was nothing in the hospital file after that point changing the diagnosis, so Dr. Olson put someone he believed to have bipolar disorder into his study for schizophrenia. Why? There was no clinical study for bipolar disorder at that time. Jeannie Kenney, the study coordinator, however, a licensed social worker, diagnosed Dan as schizophrenic on Page One of the 70 page screening. On page one, without the screening even having been completed, the question is posed, what do you think the likely diagnosis is? Based on what? The color of his eyes, his height?
Even if Dan had schizophrenia, even for those who do, the drugs themselves cause brain damage. Google “should neuroleptic drugs be banned” written by a Swedish psychiatrist Lars Martensson. It gives a very comprehensive explanation of just how they affect the brain. Thank you.
Ed Silverman
Hi Mary,
You’re welcome. Your son’s plight was a compelling tale and one that I thought others would want to read. And thanks for writing in and sharing the additional details.
I’m sorry about what occurred, but hope he left with you enough pleasant memories.
All best,
ed
Lisa Van S
Ed,
What isnt mentioned here, is that in 2006, FDA placed a Black Box Waring on Seroquel for increased risk of Suicide/Violence.
Lisa Van S
Mary,… My Deepest Sympathy to you for the loss of your son.
Edwina C
This article reads like a horror story from the Third Reich.
A Top Psychiatrist Conducts Illegal Experiments on Mental Patients.
Good Lord, have Mercy.
Sixty years ago, and the likes of Olson would have been shoveling the feeble minded into the gas chambers at Belsen.
Plus ca change..
Anne
Mary, all my condolences to you. I lost my son as well, killed by the Lilly atypical antipsychotic Zyprexa. As was learned later, the company knew of its lethal effects, namely diabetes, hyperglycemia, and death. My son died of profound hyperglycemia - we, of course, had no inkling of the peril.
I will go to my grave seeking real justice for those bottom liners at Lilly who hid this evidence. Real justice for them is long prison terms.
If you wish to correspond, please get my email from Ed.
AA
Mary and Anne,
My deepest sympathies also for the loss of your sons. As one who is tapering from psych meds due to horrific side effects, including a hearing loss, I can’t imagine what you must be feeling.
Please don’t stop seeking the truth.
AA