Wednesday, February 27, 2013

Tuesday, February 12, 2013

"Respect for person, beneficence and -- mental block": a conversation with the head of research subject protection at the University of Minnesota

From the deposition of Richard Bianco in 2007, when he was the institutional official responsible for research subject protection at the University of Minnesota.

Q. Are you aware of any physician at the University of Minnesota who has ever, in any of the research studies you're aware of, attempted to commit a patient and a few days after that sign them into a research study?

A. I'm not personally aware of that.

Q. Okay. Are you aware of the Belmont report?

A. Yes.

Q. Are you aware of any statements in the Belmont report with regard to importance of having independent assessments of the ability of patients to give informed consent?

A. No.

Q, Are you aware of the Declaration of Helsinki?

A. Yes.

Q. What do you know about it? Can you tell me a little bit about what you know about that?

A. It is one of -- it's a document, I don't remember when it came out, but it provides guidance, in the author's opinion, on how IRBs should relate to certain types of situations. It's basically a statement of ethical principles, similar to the Belmont but a little more detailed.

Q. Who's the author of the Declaration of Helsinki?

A. I think it's a group. I don't know.

Q.  Do you know which group?

A. No.

Q. And you don't know when that was adopted.

A. It's been around a while, but I don't know the dates, no.

Q. Do you have any idea at all?

A. Within the last 20 years.

Q. How about the Belmont report? Who drafted the Belmont report?

A. Well, I met one of the authors, and I can't remember his name, but again, It was another group of ethicists that met and developed some basic principles.

Q. What are the basic principles in the Belmont report?

A. Respect for person, beneficence and-- mental block.  Well, the third one escapes me right this second. Basically, it's a set of principles. Common sense principles.

Q. When was the Belmont report adopted?

A. I believe 15 or so years ago.

Q. Have you ever heard of the Nuremberg Code?

A. Uh-huh. Yes. I'm sorry.

Q. When was that adopted?

A. I don't know.

Q. Do you have any idea at all?

A. No. Sometime after World War II, I would assume.

Q. What does the Nuremberg Code say?

A. Frankly, I'm not that familiar with the Nuremberg Code.

Q. Okay. Have you ever had any training in the ethics of human subjects, experimentation?

A. Yes.

Q. What kind of training have you had?

A. Well, it's continuous training. I served on the IRB for 15 years or so, and some of that as a vice chair. I am very active in the Public Responsibility of Medicine and Research Organization, which is continuous education and those sorts of things. So did I attend a specific class? No. But I'm very involved and with PRMR and other organizations.

Q. Have you had any training in ethics, bioethics?

A. Formal?

Q. Yes, sir.

A. No.

Q. Can you tell me some of the major philosophical schools and thoughts, schools of thought with regard to bioethics?

A. Arthur Caplan school and there's the Jeff Khan school.

Friday, February 8, 2013

A make-believe investigation at the University of Minnesota

From the day that questions first began emerging about the suicide of Dan Markingson, the University of Minnesota’s General Counsel, Mark Rotenberg, has insisted that the university has already investigated the case. Most recently, in a public statement to City Pages, Rotenberg claimed that the university's Institutional Review Board (among other bodies) investigated the case and found no fault with the university, no fault with the researchers, and no “causal link between the CAFE trial and the death of Mr. Markingson." Local reporters have simply taken Rotenberg’s claim at face value, yet I have never been able to find any evidence that the Institutional Review Board did in fact investigate.

If you look at a deposition in the lawsuit brought against the university, you will see testimony that directly contradicts Rotenberg’s account. According to Richard Bianco, the official then responsible for overseeing research subject protection at the university, neither the IRB nor any other university body has investigated Markingson’s death.

What follows is an exchange between Bianco and Chris Barden, an attorney representing Mary Weiss.  (It begins on page 41 of the deposition.)

Q: Has the IRB done any investigation into the death of Dan Markingson?

A: Not a formal investigation, no.

Q: Has the university done any investigation into the death of Dan Markingson?

A: No.

And later:

Q: To the best of your knowledge, did anyone at the IRB, at the University of Minnesota, or anyone under your office investigate this case, actually look at the records and see the court documents that I’m describing, and if so, could you give me the name of that person?

A: Not to my knowledge.

Q: Nobody did that.

A: No.

Both of these accounts cannot be correct.  One University of Minnesota official is not telling the truth.  My guess is that no investigation was done.  But if Rotenberg is right and the university did investigate, why has that investigation never been made public?

Thursday, February 7, 2013

The deepening mystery over Seroquel Study 41 and Charles Schulz

The mystery over AstraZeneca’s notorious Study 41 has deepened.

Study 41, if you recall, was one of the contested studies of Seroquel that emerged in litigation against AstraZeneca.  Internal emails and documents suggested that the study was buried and the results spun, and that Charles Schulz appeared to be involved.  Here is what I wrote about the study last month for the Mad in America blog:

“Later, in a trial known as Study 41, AstraZeneca compared Seroquel XR – the extended release version of Seroquel – to placebo in patients experiencing acute schizophrenia. The University of Minnesota was one of the study sites, and Charles Schulz was the site investigator. Remarkably, Study 41 showed Seroquel XR performing no better than placebo for schizophrenia.  In emails, AstraZeneca officials refer to Study 41 as a “failed study,” or “code red.” Advisors (such as Schulz) and employees were instructed not to discuss the study. So what did AstraZeneca do? They buried it and tried it again, this time in India, Bulgaria, Romania, the Philippines, Russia, Greece and South Africa. That trial was called Study 132, and it turned out positively. So in 2007 AstraZeneca published that study in the Journal of Clinical Psychiatry. The second author of that study was Charles Schulz, who presented the data at the annual meeting of the American Psychiatric Association and served as the academic point man in company press releases.”

Mike Howard filed a complaint with the university about Schulz’s involvement in Study 41, pointing not only to the hiding of research results but to the fact that the study randomized some acutely psychotic patients to placebos, effectively depriving them of treatment for the duration of the study.  The response  to Howard came from Mark Rotenberg, the General Counsel, who wrote, “Dr. Schulz did not participate in Study 41, because no subjects were enrolled at the University.”

Rotenberg’s statement that Schulz was not involved appears to be at odds with the published study itself, which appeared in Psychopharmacology Bulletin in 2008.  In that journal article, Schulz is listed as a Study 41 investigator.  In fact, the published article has another surprise: Steven Olson is also listed as an investigator for Study 41.  Olson, of course, was the University of Minnesota principal investigator for the CAFÉ study in which Dan Markingson died.

This news raises a number of intriguing questions.  Did Study 41 actually take place at the University of Minnesota?  Was the protocol approved by the IRB?  Did Schulz and Olson each sign a Form 1572 for the FDA?  And why would Rotenberg claim that Schulz did not participate in the study when the published literature indicates that he did?

Wednesday, February 6, 2013

What the Sunshine Act really means

Alice Dreger explains.

Another day, another plagiarized dissertation

"Germany's education minister has been stripped of her doctorate after a committee of academics concluded that she plagiarised substantial parts of her 1980 thesis, which dealt with the formation of conscience." Read about it here.

Sunday, February 3, 2013

"Unethical clinical trial" by Minneapolis police?

"A half-dozen Minnesotans have sued the state and numerous law enforcement agencies, claiming that they were used as 'guinea pigs' when officers supplied them with drugs as part of a controversial police training program."  The story is in the Strib.

Saturday, February 2, 2013

How many deaths and injuries were there in the CAFE study?

On May 6, 2004, two days before Dan Markingson committed suicide in the CAFE study at the University of Minnesota, there was another "Serious Adverse Event" in the study.  Here is the letter Steven Olson sent to the IRB, along with the reply.