Olson to IRB: new documents on Scribd

After Dan Markingson committed suicide in the CAFE study, Stephen Olson wrote to the IRB explaining why Markingson was competent to consent to the study.  Here is the letter.

Nothing says "I love you" like banked mesenchymal stell cells

CellTex - Marketing Film from Tall Productions on Vimeo.
Tall Productions, a Houston specialist in cinematic wedding highlights, has produced a new marketing video for Celltex. Years from now you can re-live that special day when Celltex moved to Mexico.

Will Celltex be advertising for a Mexican bioethicist?

A warning from the FDA may have stopped Celltex from treating patients in Texas, but Mexico is just a short drive away.  David Cyranoski has the story for Nature.

"Referring to someone as 'a real tool' falls into the category of pure opinion because the term 'real tool' cannot be reasonably interpreted as stating a fact and it cannot be proven true or false."

Thus sayeth the judge.

Bad Pharma, Excellent Book

My review of Ben Goldacre's terrific new book, Bad Pharma, in the BMJ.

Desperation at Eli Lilly?

The loss of patent protection for Zyprexa has hit Lilly hard.  Have a look.

Max Kampelman, diplomat and ex-guinea pig, is dead at 92

Max Kampelman was well-known and respected for his career as a diplomat and nuclear arms negotiator. Less widely known is his experience as a research subject in the University of Minnesota starvation studies during World War II.  Kampelman was a conscientious objector and a member of the Civilian Public Service, which supplied subjects to the university. Todd Tucker documented the study in his excellent book, The Great Starvation Experiment, which I reviewed in The American Prospect in 2007.  Here is an excerpt.

"Clinical research has always depended on the availability of people whose circumstances were bad enough that medical experiments looked like a good option. Today it is often the poor who are recruited, but during World War II it was conscientious objectors. The Civilian Public Service (CPS) was set up as an alternative to the military for conscientious objectors, many of whom belonged to pacifist denominations such as the Quakers, the Mennonites, and the Brethren. Many CPS jobs involved menial labor, but another option for objectors was to volunteer for medical research, which was conducted at camps all over the United States. Some volunteers gargled pneumonia-infected sputum. Others wore lice-infested underwear in order to contract typhus. Another group of participants allowed mosquito-filled boxes to be strapped to their bellies so that they would get malaria. And as Todd Tucker documents in his thoroughly absorbing book, The Great Starvation Experiment, one extraordinary group at the University of Minnesota was intentionally starved."

"The Minnesota study was conducted toward the end of the World War II in order to understand how best to treat malnourished citizens in the newly liberated countries of Eastern Europe. The experiment's chief scientist, Ancel Keys, placed 36 young men on semi-starvation rations for six months. The subjects emerged looking like concentration-camp victims, but the drama in Tucker's book comes from the psychological effects of starvation: the slow narrowing of desire, the obsession with food, the disturbing dreams of cannibalism. One subject wound up "accidentally" chopping off his fingers with an ax so that he would be dropped from the trial."

Crowdsourcing hidden research data

The BMJ is fighting back against pharmaceutical industry wrongdoing.  In the UK, the House of Commons Science and Technology Committee is holding a new hearing into the implications of missing clinical data on patient safety. It is looking for evidence. To that end, the BMJ is asking for reports of the pharmaceutical industry hiding or suppressing data.  It says, "We would like to see any report of any obstruction, from any researchers or companies, which you are aware of. This can be from your own work, the academic work of others that you have read, or media reports. Our remit is broad."

This is an issue familiar to anyone who has followed the Seroquel (quetiapine) controversy in the Department of Psychiatry here at the University of Minnesota, of course, where the harm to patients is especially vivid. (It does not get much more vivid than suicide.) Seroquel is mentioned on the list of examples the BMJ has collected.  But there may be other examples. I would encourage you to submit them using this form..

Corrupt German doctors

"The German Medical Association has investigated just under 1,000 doctors suspected of corruption over the past few years." Read about it here.  (How many have doctors been investigated by professional bodies in the US?  Anyone?)

University of Minnesota Mythbusters?

I don't think so.

Indian guinea pigs in the dark on drug trials

The Zyprexa bioethicists

It’s no secret that Eli Lilly has been very good to the University of Minnesota’s Department of Psychiatry.  Just find a couple of the relevant databases, punch in some names, and see how many hundreds of thousands of dollars Lilly has paid out.  (Hint: some of the names you might want punch in are Schulz, Olson, Crow, and Orr.)  The rationale is not hard to figure: Lilly has produced some spectacularly lucrative psychiatric drugs, such as Zyprexa and Prozac, and academic “thought leaders” have been the key to its marketing strategy.  

But it’s not just academic psychiatrists who are on the take.  Academic bioethicists have been on the Lilly payroll for years – namely, Georgetown’s Tom Beauchamp and Yale’s Robert Levine.  Beauchamp and Levine were hired after Lilly was busted for testing the safety of new drugs on homeless alcoholics.  (Which is ethically just fine, in case you were wondering.)  Most readers of their books and articles do not know this, because unlike payments to physicians, payments to bioethicists are not governed by sunshine laws or tracked by public databases, and most bioethicists don’t disclose their industry ties in their published articles.   Take, for instance, the special issue of the Hastings Center Report on research ethics published this week, in which Beauchamp has co-authored two articles.  There is no mention whatsoever of his involvement with Lilly.

Such secrecy is not uncommon.  The financial ties between ethicists and pharma have been well-documented for years, yet for some reason, bioethics journal editors simply do not take the issue seriously.  Not only is this an embarrassment to the field; it is an insult to patients who have been injured by Lilly’s illegal marketing and fraudulent clinical trials.

"Chubby little loser"

In the latest issue of The Hastings Center Report, bioethicist Dan Callahan suggests that we should combat the obesity epidemic by stigmatizing people who are overweight.  (Apparently, this was not a joke.)

Addendum: You've also got to read Dan O'Connor's "Dan Callahan Thinsplains Obesity."

Z is for Zyprexa

Also Zoloft, Zocor and Zyban. Here's why.

Yale bioethics, brought to you by Pepsi

Human subjects protection, fMRIs, and a refreshing beverage, courtesy of your friends at Yale and Pepsi.

The success of frightened professors

This sounds depressingly familiar.

The FDA approved devices to administer electric shocks to disabled children? Seriously?

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Andy Mannix is a finalist for a 2013 GLAAD Media Award

Congratulations to the always-excellent Andy Mannix, a City Pages journalist and University of Minnesota J-school alum.  Andy is a finalist in the 2013 GLAAD Media Awards for this article on Chris Kluwe.

The compliance industry turns to the mentally ill

Have a look.

Premack Awards suspended

A sad announcement for Minnesota: after 35 years, the Minnesota Journalism Center and the University of Minnesota School of Journalism & Mass Communication have suspended the Frank Premack Public Affairs Journalism Awards Program. 

Which do patients hate more: pharma or health insurance companies?

You might be surprised.

Research subjects strike back

Fifty-three former research subjects, outraged that pharma is hiding the results of clinical trials, have written to the European Medicines Agency demanding change.  Read the petition here.  (Also, Pharmalot reports on  a "voluntary industry code" for transparency here.)

And that’s the news from the Department of Psychiatry, where all the nurses are “supportive of research” and “all the patients are reviewed for possible research candidacy”

In the business of clinical trials, the most valuable commodities are the research subjects.  Filling clinical trials is hard, and filling them quickly is even harder.  That’s why in 2000 a clinical investigator told the HHS Office of the Inspector General that research sponsors were looking for three things from research sites: “No. 1—rapid enrollment.  No. 2 — rapid enrollment.  No. 3 — rapid enrollment.”

Back in the early 2000s, the University of Minnesota’s Department of Psychiatry was having so much trouble getting research subjects that Quintiles, a Contract Research Organization, had put it on probation.  Perhaps the department’s difficulty convincing subjects to sign up for trials should not have been a surprise, given its alarming history of research scandals.  Yet by December 2003, the Department had managed a 180-degree turn.  In fact, it had become so successful in getting subjects into trials that Quintiles had profiled it in a CAFÉ study webcast.  How did the Department manage to become such an aggressively successful recruiting site?

A hint emerges in this document from the lawsuit against the University of Minnesota brought by Mary Weiss over the suicide of her son, Dan Markingson.  The document, dated April 14, 2003, is labeled “CAFÉ Study Coordinator Teleconference,” and it mentions a number of strategies for recruiting subjects.

First, the document references a discussion of “ways to utilize subjects for multiple studies.”  The phrase “multiple studies” should set off a red flag.  Enrolling severely mentally ill subjects in multiple industry-funded studies was exactly the strategy of former University of Minnesota psychiatrist Faruk Abuzzahab, who was eventually found to be responsible for the deaths and injuries of 46 patients.   

Second, the document discusses a “newly-added 16 bed psychosis specialty unit” where all nurses and staff are “supportive of research” and “all patients are reviewed for possible research candidacy.”  Every patient?  Remember, patients with psychotic illnesses are among the most vulnerable patients in the hospital.  Because of their thought disorders, they are often unable to understand and appreciate the risks of research.  Yet according to this document, every patient on the psychosis unit is evaluated for his or her suitability for research studies -- and perhaps even multiple studies.  How exactly do the Minnesota psychiatrists accomplish this?

Apparently one way is to have research staff “attend morning report before inpatient rounds take place,” in order to “identify any possible subjects who might be eligible for studies.”   Yet again, this statement should raise alarm bells.  Morning report is a time for discussing the care of patients, where private medical information is revealed.  Why should research staff working for pharmaceutical companies and Contract Research Organizations be given privileged access to the private health information of hospitalized patients?  Of course, privacy violations were at the heart of Mike Howard’s complaint about Stephen Olson to the Board of Regents, which was dismissed by the General Counsel.

This is an alarming document, but even more alarming is the fact that nobody at the University of Minnesota is willing to look into the issues it raises – not the Board of Regents, not the Research Subject Advocate, not the Research Integrity Officer, and not the Research Ethics Consultation Service.  At the very least someone should be asking the question: how do we know that the suicide of Dan Markingson in the CAFÉ study was an isolated case?

Hush and hear: a note about Mary Weiss

Last April the filmmaker and photographer Donal Mosher posted a moving note about Mary Weiss, the mother of Dan Markingson, on his blog, Ghosttype. It is well worth reading again.

Something’s not right here: part 3 (or, Don't you usually ask permission to see a subject's medical records before you enroll them in a study?)

Were Dan Markingson’s privacy rights violated in the CAFÉ study?   As I pointed out in my request for an investigation by the university’s Research Ethics Consultation Service, the Health Insurance Portability and Accountability Act (HIPAA) prohibits health care providers from releasing a patient’s private health information for use in research without the express written authorization of the patient. Violation of that law is a felony.  This means that before AstraZeneca (the study sponsor) or Quintiles (the CRO managing the study) could see any of Dan Markingson’s health information, they would have needed his signed authorization.  At the time of the lawsuit by Mary Weiss against the University of Minnesota, there was no record of any such authorization in Markingson’s medical records.

Yet when Mike Howard filed his complaint about Stephen Olson to the University of Minnesota, Mark Rotenberg produced a written HIPAA authorization dated November 24, 2003.  The emergence of a HIPAA authorization at such a late date is odd.  If the University of Minnesota had a HIPAA authorization, why didn’t it produce that document when Stephen Olson was being grilled on HIPAA in his deposition?  But equally odd is the date on the authorization, which comes three days after Markingson was enrolled in the CAFÉ study.   That is three days too late.  Subjects need to provide authorization before they are enrolled, not after.  Of course, if Quintiles and AstraZeneca had not been given access to Markingson’s health information before he gave his authorization, they would not have even known if he was eligible for the study.

None of this is justified or explained in Rotenberg’s letter.  Yet University of Minnesota officials appear to have accepted it without question.  Why is Rotenberg’s response seen as an adequate explanation? 

Petition launch: All trials registered, all results reported

You can find it here.

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Something's Not Right Here: Part 2 (or, "Did anyone in your CAFE study sign a HIPAA authorization form?")

In his 2010 complaint to the University of Minnesota’s Board of Regents, Mike Howard argued that Dan Markingson’s health privacy rights had been violated in the CAFÉ study. He pointed out that Stephen Olson had testified in a deposition that he was unaware of how HIPAA (health privacy) requirements applied to clinical trials.  Mark Rotenberg replied: “A complete review of Dr. Olson's deposition transcript, consisting of hundreds of pages, simply does not support this allegation.

Really?  Have a look at what the deposition actually says.  (In what follows, I have corrected spelling errors and edited out the attorney’s objections.)

Q.   Isn't it in fact the case that Dan was supposed to sign a HIPPA authorization and he never was asked to do so and never did so in your study?

A.   I'm not aware that there were any documentation failures like that, no.

Q.   (BY DR. BARDEN) Did anyone in your CAFE study sign a HIPAA authorization form? 

A.   I don't know.

Q.   So you don't know if Dan was the only one who did not sign a HIPAA authorization?

A.   I don't know.

Q.   Do you know what the University rules are with regard to conducting research when a subject has not signed a HIPAA authorization form?

A.   No, I don't know what the consequences are or the rules.

Read the entire deposition transcript here.

Something's not right here: Mark Rotenberg and the Board of Social Work

I’ve just posted copies of Mike Howard’s 2010 complaint to the University of Minnesota’s Board of Regents about Stephen Olson, as well as the reply (nearly a year later) from Mark Rotenberg, the General Counsel for the university.  Both documents are worth re-reading in light of the recent “corrective action” against Jean Kenney, Olson’s study coordinator, issued by the Minnesota Board of Social Work. There is a lot to comment on here, but let me just point out one striking disagreement between Rotenberg and the Board of Social Work.

In his complaint, Mike Howard argues that Olson had Kenney dispense prescription drugs and assess their side effects even though she had no medical training.  According to the Board of Social Work, which responded to a similar complaint, Howard was absolutely right.  The Board states that Kenney was unqualified to dispense prescription drugs, monitor side-effects or handle adverse events.  In fact, her actions were in violation of the university's own policy.  Yet Rotenberg claims that for Olson to delegate these medical responsibilities to Kenney was completely appropriate and “entirely within IRB and Good Clinical Practice guidelines.”

Something’s not right here.

You can look at the documents for yourself – there is a lot more to see -- but here is a summary of this particular disagreement.

In his complaint, Howard writes:

Dr. Olson delegated the dispensing of very powerful antipsychotic drugs to a study coordinator not licensed to dispense drugs, who had received no prior training nor education regarding how these drugs are taken, the severe side effects that an enrollee might experience, consequences for stopping the drug unexpectedly and the experience to monitor whether the study drugs are appropriate for the symptoms being treated and are having the desired effect.

Here is what Rotenberg wrote in reply to Howard:

Dr. Olson was assisted in the CAFE Study by a research coordinator who had a bachelor's degree in psychology and a master's degree in social work. As the study coordinator, this person worked under the close supervision of Dr. Olson as the principal investigator.

Throughout the study, Dr. Olson was responsible for "dispensing" the medication in his capacity as principal investigator. Under Dr. Olson's supervision, the study coordinator merely gave the pre-packaged and marked bottles of pills to Mr. Markingson. Mr. Markingson, upon returning to Theo House, the half-way house where he resided, would then give the bottle of medication to the Theo House staff who oversaw the delivery of the medication to him on a daily basis, and helped assure that he was taking the right doses at the right time.

Dr. Olson was responsible for the prescription of the medication under study protocol. He discussed the medication side-effects with Mr. Markingson. He also discussed these medications with the study coordinator and closely supervised her activity. This is standard procedure in out-patient clinical trials and was conducted entirely within IRB and Good Clinical Practice guidelines. Neither the IRB nor the FDA had any questions that proper procedures were followed for dispensing of study drug.

 But the Board of Social Work had very different response:

 

Although Licensee had no formal medical training or experience with respect to obtaining medical histories or handling adverse drug events, Licensee regularly completed forms, gathered information, and performed tasks that were beyond Licensee's competence and scope of practice as a clinical social worker. Licensee also made numerous documentation errors in the performance of these tasks.

Licensee dispensed legend prescription drugs without authorization and in violation of the University's policy.

Between November 24, 2003 and April 28, 2004, Licensee completed forms assessing the Barnes Rating Scale for drug-induced akathisia, as well as weight, vital signs, and waistlhip/height measurements. Licensee also completed the Simpson-Angus Abbreviated Examination of gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, and tremor.

On nine occasions, beginning on December 5, 2003, Licensee completed the Adverse Event/Medical Diagnosis form, which called for a "clinician rating of severity" for orthostatic faintness, dry mouth, constipation, sialorrhea, gynecomastia, galactorrhea, sex drive, sexual arousal, sexual orgasm, incontinence/nocturia, urinary hesitancy, skin rash, hypersomnia, weight gain, akathisia, and akinesia. On two additional occasions, Licensee delegated the task of completing this form to a social work intern, who Licensee was supervising.

It is no surprise that Rotenberg did not comment on these findings in his statement to the press about the corrective action against Kenney.  I hope to post more on Rotenberg’s response to other aspects of Howard’s complaint very soon.