Getting to the truth

There was an interesting array of topics at last week’s Advancing Ethical Research conference sponsored by Public Responsibility in Medicine and Research (PRIMR), ranging from basics of Institutional Review Boards (IRB) to ethics of Ebola trials, which was excellent.

Given my ongoing interest in the Markingson case at the University of Minnesota (UMN) (see below), I was immediately attracted to the session on vulnerable subjects in medical research. One of the speakers there was Ernest Prentice, PhD, an expert in research ethics at University of Nebraska who lectures widely on that topic. As he did at the Association of Clinical Research Professionals (ACRP) conference last spring, Dr. Prentice chose to illustrate his lecture on vulnerable subjects with the story of Dan Markingson, a young man with schizophrenia who was enrolled in a clinical trial of antipsychotics and who subsequently committed suicide. A judge had given Dan a choice of commitment to a psychiatric institution or following the recommendations of his treatment team, led by Dr. Steven Olson. Just two days after being deemed incapable of consenting to Risperdal (antipsychotic treatment), Dan was enrolled on the CAFÉ trial, a comparison of three antipsychotic medications for schizophrenia, sponsored by AstraZeneca.

This case illustrates many aspects of clinical research, some of which I’ve covered before, such as Informed Consent and Conflicts of Interest.

So imagine my surprise when this speaker gave a strong defense of the UMN’s IRB without disclosing on his slides that he was paid almost $14,000 as an expert witness for the UMN in a suit brought by Markingson’s mother, Mary Weiss. (In fact, at ACRP, his slide declared, “I have no financial relationship with respect to this educational activity.” When I asked him about this apparent conflict of interest (COI) in the Q&A session, Prentice replied, “As an expert witness, you obviously get paid, to be an expert witness. So clearly the UMN, through their insurance company, paid me to assist the defense of the IRB piece…so that would be, if you want to call it a COI, you could choose to characterize it that way.”

I was also very disturbed at the numerous errors in Dr. Prentice’s slides, which bolstered his contention that there was nothing wrong with this psychotic young man being enrolled in a clinical trial—Dan’s alternative to commitment. For example, Prentice states, “DM’s enrollment in the CAFÉ Protocol was approved by David Pettit, his court appointed social worker,” but fails to mention that this social worker didn’t even see Dan until 5 days after he was enrolled on the trial. Or “DM’s last study visit was on 3/28/04. The record indicated that he did not display any signs of depression, paranoia or delusions.” In fact, Dan was seen by Dr. Olson on 4/9/04, who noted, “ADLs (activities of daily living) had deteriorated over the last few months, and often looked more disheveled.” In fact, Olson went on to recommend an additional 6-month extension of Dan’s commitment order by the court. [A list of apparent errors appears below.]

When I asked Prentice about these errors, he replied, “…my points on my slides are based upon depositions that I read, and I read every one of the depositions, all the expert reports, the FDA audit, the IRB documentation, informed consent form, etc. and the complaint, of course, and then subsequent to that, all of the correspondence that has come out of that particular tragedy, a lot of it precipitated, as you know, by Carl Elliott.” (Dr. Elliott is a bioethicist at the UMN, who has written extensively about this case and called for an independent outside investigation.)

Subsequently, Prentice stressed that his comments in defense of the UMN referred only to the IRB. “I looked at everything and I was satisfied with the quality of the IRB review.”

Even if we only focus on the IRB’s role, there are problems with Prentice’s defense of it. First, the director of the IRB, Moira Keane, was asked in her deposition (p. 96), “So, it’s not the Institutional Review Board’s purpose to protect clinical trial subjects, is that what you are saying?” Keane’s response, “That’s true.

Asked about Keane’s comment, Prentice said, “I read her deposition. The role of the IRB is obviously to protect human subjects. Clearly. And I would be surprised if Moira Keane had said that in any context.”

Given Dr. Prentice’s defense of the UMN’s IRB, I subsequently asked him about Dr. David Adson, who was chair of the IRB overseeing the CAFÉ trial, and responsible for investigating Dan’s death.

Adson received money from AstraZeneca (the CAFÉ study sponsor) and was in the same department as Olson and Charles Schulz (Adson’s department chair in the UMN Department of Psychiatry, and co-investigator on the CAFÉ study). Adson also directed the center where the CAFE study was housed. Despite all this, Adson claimed on the IRB report that he had no conflict of interest⁠⁠ (COI). I asked Prentice, “Don't you think that was worth mentioning as a problem with the IRB?” Prentice said that he was unaware of Adson’s role—that this became public after his involvement with the case.

The problem I have with these explanations are that a) as an expert witness, I might have expected Prentice to perhaps know a few more details about the IRB he was defending and b) I would have expected someone who continues to teach about a topic, using Markingson as illustrative of issues of research in vulnerable subjects, to have kept up with news and have updated his material. While Dr. Prentice may not be paid for his lectures, he certainly derives benefit by registration being waived at the conferences where he speaks and by further enhancing his stature as a nationally recognized research ethics expert.

It is perhaps telling that Dr. Prentice gave another lecture last year at ACRP, titled “Advice from a Hired Gun in Clinical Trial Litigation.” It is also telling that he did not clearly declare his own conflicts of interest at either ACRP or PRIMR. This does not inspire confidence in such conferences as paragons of training in research ethics.

Prentice claims -1

 

Prentice claims - 2

 

Prentice claims - 3

 

Prentice - 4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Previously in this series:

A Clinical Trial and Suicide Leave Many Questions: Part 1: Consent?

Part 2: Investigator Responsibilities

Part 3: Conflict of Interest

Part 4: The University of Minnesota’s Response

Part 5: The Case of the Mysteriously Appearing Documents

Part 6: The Run-Around, or Why I Now Call for an Independent Investigation of University of Minnesota

A New University of Minnesota Mystery-The Curious Departure of Mark Rotenberg

Yahrzeit – Reflections on Dan Markingson’s Legacy

Covering Clinical Trials: a message for journalists and critical readers

How Not to Run an Op-Ed Page

Anti-Psychiatry Prejudice? A response to Dr. Lieberman

Minnesota Attorney General Confirms They Did Not Exonerate UMN in Markingson Death

Further reading:

University of Minnesota Should Investigate Suicide in Clinical Trial, Scholars Argue

Letter by Trudo Lemmens et. al.

Investigate the Death of Dan Markingson

A referenced summary of the Dan Markingson case

Credits:

"Getting to the Truth" courtesy Xoe Craft

“Molecules to Medicine” banner © Michele Banks