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A Clinical Trial and Suicide Leave Many Questions: Part 5: The Case of the Mysteriously Appearing Documents


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This series uses the story of Dan Markingson’s participation in a clinical trial of anti-psychotics at the University of Minnesota, his ultimate suicide while participating on the study, and subsequent events as a case study in which to explore various aspects of clinical trial conduct. In previous posts, we’ve looked at issues of “good clinical practices” and ethics: consent, investigator responsibilities, and conflicts of interest. In the last post, we examined the University’s response. Now we return to the importance of careful documentation of consent.

Since I last wrote on the lapses in good clinical practices at the University of Minnesota, involving the suicide of a clinical trial participant, Dan Markingson, more disturbing documents have come to light, provided and contextualized by Professor Carl Elliott. Hard to imagine, I know…but this single case can provide a lifetime of lessons on clinical trial conduct, oversight, and ethics.

HIPAA Security Guide

This week’s episode looks at several mysterious documents, asks why some are only appearing now, and brings you more questions raised by their contents.

 

First, look at these HIPAA consent documents:

Single Page HIPAA in Markingson Chart Certified by Medical Records Department at Fairview April 5, 2011

Disputed HIPAA document with Signature

 

 

 

 

 

 

 

 

 

What do you notice?

One lacks a signature, and the Fairview Hospital medical records department is both certifying its authenticity and that there was no signed HIPAA consent page on Dan’s record. The second form—is signed and dated. The only explanation, woefully unsatisfying, comes from family friend Mike Howard, who noted: “Mary [Weiss]’s attorneys as well as Mary had received about three (3) different “Certified” sets of records and each one was different or had pages added or subtracted. So much for certification of study records.”

Now note the date on the HIPAA consent. There are a couple of concerns with this document. The first, is that this dated consent was never given to Mrs. Weiss nor her attorneys in her suit against the university. How did this magically appear in 2011, only in response to a complaint by Mr. Howard alleging misconduct by Dr. Olson?

Other documents from that suit, available on Scribd, have “Bates” numbers, which are used to identify medical and legal documents. This signed HIPAA consent lacks such an identifying number.

Mark Rotenberg, counsel for the UMN, in defending Dr. Olson and the university against charges by Mike Howard, responds to Mr. Howard’s complaint (almost a year later) by noting that the HIPAA consent was signed November 24. In that same letter, Mr. Rotenberg further notes that Dan consented to participation in the trial on November 21. So I read this as the University’s counsel confirming Mr. Howard’s assertion that Markingson’s mental health records had been released to the study coordinator, working as an agent of AstraZeneca through Dr. Olson, without Dan having signed a HIPAA release. Howard reiterates, “There is absolutely no paper document or record anywhere that states Dan agreed to be interviewed by Jean Kenney, Liz Lemke or anyone else connected with the CAFE’ study. No record in any of his hospital notes indicating that he possibly gave ‘verbal’ authorization to anyone connected with the CAFE’ study to approach him.”
I await Mr. Rotenberg’s explanation. [His office was contacted by me for this story].

There is another problem with the HIPAA consent, which, in and of itself, could represent a felony. The HIPAA regulation “requires that an Authorization contain either an expiration date or an expiration event.” This has neither. It appears that the University is at risk for significant civil and criminal penalties. A second CAFE Study family provided Carl Elliott with an identical, unsigned HIPAA consent form, and again with no expiration.

“Evaluation to Consent” forms

The next document mystery involves these forms in which Jean Kenney, the social worker responsible both for study recruitment and a psychiatric evaluation regarding a “volunteer’s” ability to understand and consent to participation, administered to patients.
Look at these evaluation forms:

Evaluation to Consent without initials

Evaluation to Consent with initials

 

 

 

 

 

 

 

 

What do you notice?

They appear identical, except for initials on one, suggesting they might have been xeroxed and used as a template.

Then a 3rd form appeared:

Evaluation to Consent-anonymous CAFE study member

 

It, too, is identical–but lacks initials or a hospital unit number. But it was given to Dr. Elliott by someone who, as yet, feels a need for anonymity. Other families have contacted Dr. Elliott or posted on the Community Alliance for Ethics in Minnesota Psychiatry Facebook page that they have identical forms as well, though this has not yet been definitively confirmed.

What do these duplicate forms mean?

The HIPPA forms are troublesome because they indicate possible breaches of patient confidentiality regarding psychiatric illnesses. The requirement for an expiration date was a federal requirement at the time of the study, as verified by the HIPAA web site. Each of these problems is potentially a felony.

The seemingly duplicated  evaluations to consent are even more problematic. It is implausible that patients gave identical responses to these questions of their understanding and ability to consent. Using duplicated forms would call into question the competence of the patients to consent, a contested point in Mary Weiss’ suit against the UMN. As Dr. Elliott notes, the “evaluation to consent” forms have been submitted to official research oversight bodies, which have relied on them to make judgments about the conduct of the studies.

I would extend the concerns further. If the investigators allowed their staff to use identical forms and claim that different patients provided identical answers, then this would be far more evidence they provided inadequate oversight and did not fulfill their responsibilities as Principle Investigators. It would also call into question the work that this team did on other clinical trials, including the NIH funded CATIE trial.

The university is state and federally funded. Given that, a bit of transparency would seem in order. One of the most troublesome aspect of this case for me is the response of the University to questions being raised. In 2010, eight faculty members sent a letter to the Board of Regents requesting an outside investigation. None was done.

Dr. Elliott has bravely persisted in methodically raising concerns as new evidence emerges, each time posting documents of concern on Scribd for anyone to evaluate. He is  still requesting an outside investigation. Instead of doing so, the University has brushed aside Dr. Elliott’s concerns. In the latest example, Dr. Frances Lawrenz, the Associate Vice President for Research replied to the emergence of this new evidence:
“Our research misconduct policy has a ‘statute of limitations’ of 7 years…Since the matters covered in your letter occurred more than seven years ago, the material you present is outside the purview of the policy. In addition, your concerns about the consent evaluation process and possible HIPAA violations do not appear to fall under the definition of research misconduct (i.e., alleged fabrication, falsification or plagiarism), regardless of when the events occurred.
[Note: I attempted to reach Dr. Lawrenz for comment and was told she would not speak with me.] I am unpersuaded with the response I subsequently received via the PR person apparently directed to call me by Mr. Rotenberg’s office.

Conclusion

It is difficult in this case, as with much of life, to tell with total certainty “where truth lies.” The reluctance on the part of the Office of Research, the Office of the President, the Office of the Counsel, and the Board of Regents of UMN to fully and transparently examine new evidence is extremely troubling, though. Without such a transparent examination, there is no guarantee that the clinical investigational staff did not commit breaches of research ethics and of law, and has not continued to do so, perhaps putting other vulnerable patients at undue risk.
When I started reading about this case, it was as an academic endeavor, seeking a case study for my blog. I did (and do not) not know any of the parties involved. Yet the more I have learned, the more outraged I have become.

I am angered by the thinly veiled threats towards Dr. Elliott (e.g., Mr. Rotenberg’s “What is the faculty’s collective role in addressing factually incorrect attacks on particular University faculty research activities?”

I am saddened by what appears to me to be violations of the trust of vulnerable patients and of research ethics. As I have become immersed in the case, it has become clear that it provides a lifetime of study and discussion about what not to do during the course of a clinical trial. It is also clear to me that more patients than Mr. Markingson likely were harmed at the UMN by: enrolling participants with contested ability to consent; having financial incentives that encourage keeping someone on a trial when it appears they are not responding well; approving and supporting protocols that have seemingly disproportionate risks, e.g. “The Use of Quetiapine (Seroquel) in the Treatment of Social Phobia: Public Speaking Environment.

And, unfortunately, it appears that UMN believes, as do many other institutions, that protecting itself from scandal and its consequences comes first and foremost and that, like the big banks, that it is too big to be punished.

Suggested reading:

Carl Elliott’s important new letters:

Request that FDA Office of Scientific Investigation to investigate “evaluation to consent” forms for CAFE study

Letter to HHS Civil Rights About Possible HIPAA Violations

Credits:

HIPAA image: purpleslog/Flickr

Judy Stone About the Author: Judy Stone, MD is an infectious disease specialist, experienced in conducting clinical research. She is the author of Conducting Clinical Research, the essential guide to the topic. She survived 25 years in solo practice in rural Cumberland, Maryland, and is now broadening her horizons. She particularly loves writing about ethical issues, and tilting at windmills in her advocacy for social justice. As part of her overall desire to save the world when she grows up, she has become especially interested in neglected tropical diseases. When not slaving over hot patients, she can be found playing with photography, friends’ dogs, or in her garden. Follow on Twitter @drjudystone or on her website. Follow on Twitter @drjudystone.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. Steven 6:30 pm 03/12/2013

    Very complicated case.
    This is in the legal area, and I am sure all evidence is being reviewed by legal counsel.
    Research is so complicated, expensive, and regulated in the US, it’s unlikely to continue in the future.

    Link to this
  2. 2. Judy Stone in reply to Judy Stone 10:33 pm 03/12/2013

    Perhaps evidence is “being reviewed” by counsel, but thus far the UMN counsel’s stance has been very disappointing and has inadequately addressed these and other concerns. Further, given that the same research team was involved in other clinical trials, including those funded by NIH, there is concern that similar breaches occurred on those trials as well. There really needs to be a thorough and independent, outsideinvestigation at this point.

    BTW, the research standards that appear to have been breached are not unique to the US. They are pretty basic ethical and record keeping standards and are not, in and of themselves, that cumbersome. I know. I was the Principle Investigator on many clinical trials while also in solo practice, yet I obtained all the informed consents and did almost all the assessments myself. I felt that was my obligation to the patients–and I had a very low threshold for dropping someone who was not doing as well as expected. I felt I had an ethical responsibility to behave that way.

    Link to this
  3. 3. CarlElliott 11:17 pm 03/12/2013

    Thank you, Judy Stone, for helping to call attention to this appalling case of research misconduct at my university. If readers of this blog want to know what they can do to help, I have a suggestion: sign the petition for an investigation of the university. It was started by Mary Weiss, the mother of Dan Markingson, and her friend Mike Howard. You can find it here:

    https://www.change.org/petitions/governor-mark-dayton-of-minnesota-investigate-psychiatric-research-misconduct-at-the-university-of-minnesota-2

    or at this shortened link:

    http://chn.ge/13TtenX

    Link to this
  4. 4. Judy Stone in reply to Judy Stone 11:37 pm 03/12/2013

    Thank you, Dr. Elliiott, for being so clear in your work and writings. Your thoroughness, sense of justice and ethics, and caring, have been an inspiration to me as well as others. I will continue to try and shed light not just on this trial, but on others that may have been tainted as well. Learning about this case inspires more determination to find the truth.

    Link to this
  5. 5. erbarker 4:31 am 03/13/2013

    I empathize with poor Mr. Markingson having had two strokes, that me unable to understand consent forms. But, at the same time I personally prefer treatment, or even taking my on life to the thoughts of a padded cell for the rest of my life. The whole sorry episode should be looked at from Mr. Markingson point of view. Had he been able to speak for himself which would he have preferred? Life in a padded cell or, as I, death.

    Link to this
  6. 6. meegwich 6:59 am 03/13/2013

    “I expect to pass through life but once. If therefore, there be any kindness I can show, or any good thing I can do to any fellow being, let me do it now, and not defer or neglect it, as I shall not pass this way again.” William Penn

    Thank you Judy for picking up Dan’s cause and giving it the excellence that you have. I’m not an overtly religious man; but, I believe we sometimes find Angels here on earth, and you and Carl Elliott have certainly earned your wings. Thank you. Mike & Mary

    Link to this
  7. 7. Judy Stone in reply to Judy Stone 9:21 am 03/13/2013

    Mr. Markingson did not have a stroke; his mother did. There were other drug options that he was not offered, nor was he dropped from the clinical trial. It is customary to drop people when they are not responding well to treatment, and switch them to alternative medications. This was not done at the UMN, which I find shocking.

    Link to this
  8. 8. kaebomb 11:31 am 03/13/2013

    Great article, Dr. Stone! Since Reagan’s times, people with mental illness have been very marginalized and neglected. It is wonderful that someone with your expertise and insight cares and is revealing what happens to them.

    Link to this
  9. 9. dplyler1987 12:52 pm 03/14/2013

    For someone who claims to be well versed in research I’m surprised how little you seem to know about consent. When people are admitted to a teaching hospital they are eligible to be asked about clinical trials unless they request not to be contacted. So unless he opted out when he was admitted, I’m unsure the mystery around how clinicians approached him for a trial. He was in their system. At a research institution. They saw his condition and obviously felt he could benefit from this trial. Then, a few days later, once treatment had started to get him back to a normal state, and when he was able to consent for himself, he signed a HIPPA form. Hence the delay. Let’s all stop pretending to be outraged here.

    Link to this
  10. 10. Judy Stone in reply to Judy Stone 3:03 pm 03/14/2013

    Actually, you are not correct. You do not agree to be contacted at a teaching hospital either, unless they specifically ask you to allow this at the time of admission. There are many apparent errors in the UMN processes.

    Link to this
  11. 11. meegwich 5:17 pm 03/14/2013

    @dplyer1987 Dan Markingson was brought to the University of Minnesota already on what’s called a 72HR hold. He didn’t ask to be brought there. The hospital that received him from a 911 call had no available room, and thus he was transferred to the University Hospital which had room. Upon arrival he NEVER signed a Hospital HIPAA form or any type of personal release, the HIPAA in question never appeared in his hospital records nor in the study records. It only magically appeared a few years ago. Please get your facts straight before engaging your fingers…

    Link to this
  12. 12. mmanion 2:37 pm 03/26/2013

    Whether or not there was research misconduct, as a Minnesota taxpayer, I am appalled by the U of MN’s behavior in this. To withhold documents for years and then claim they fall outside of a self-imposed statute of limitations is certainly balls-y. They appear to be treating this as a joke, not even bothering to verify the validity/elementary level credibility of the documentation they (withhold and then) present. It’s extremely disturbing and I hope there is some reasonable explanation for what appears to be crass hubris. Yet another reason the U should welcome an independent investigation, as they claim to be innocent of all misconduct and to be the victims of a media smear campaign–easily remedied by an independent, impartial investigation, right?

    My perspective on this may differ from researchers, however, as I am the director of a patient advocacy group for a rare disorder. We educate patients on the importance of clinical research and attempt to help recruitment efforts, which are a challenge in rare diseases. While we support research efforts on behalf of our patient community, that support is predicated on assurances that risk/benefit assessments are done in an unbiased manner and clearly communicated to patients and that adequate oversight, as required by state and federal law, is in place. It appears that the U of MN feels it is above those laws–probably in large part because the courts have said they are by determining that the U and its IRB are ‘immune’ from prosecution as state ‘agencies.’ They are not immune from patient loss of confidence, however. Until there is assurance that there is some accountability for those tasked with holding others to account at the U of MN (namely the IRB that appears to have been totally derelict in its duty even in the face of federal and state legal violations), it would be extremely difficult to ethically direct patients to research efforts at the U of MN. And believe me, the word gets around in the advocacy community. The U’s ham-fisted attempt to protect researchers in one department is going to have a chilling effect on recruitment efforts into ethical and legitimate research efforts in other departments. I’ve already been asked by colleagues from other organizations about the research misconduct ‘situation’ at the U of MN. Again, another reason the U should welcome an independent investigation to restore faith in it’s process.

    Link to this
  13. 13. Judy Stone in reply to Judy Stone 3:19 pm 03/26/2013

    Thank you so much for your perspective. Has an advocate of clinical research trials–and having participated myself–I am saddened and angered by the UMN’s apparent stonewalling. The participation in cancer clinical trials is < 5% among adults, for example. We need to reassure volunteers that they will be well cared for. I fear that problems like this will, understandably, discourage trial participation.

    Link to this

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