healthy4u: irb

The University of California - Davis just keeps supplying us with lessons about problems with leadership and governance in major health care organizations. Our latest example comes from <a href="http://www.sacbee.com/2012/07/22/v-print/4648415/2-uc-davis-neurosurgeons-accused.html">a story</a> in the Sacramento (CA) Bee. A Bizarre Series of Surgical Experiments It started with two neurosurgeons who embarked on an extremely unorthodox treatment program, <blockquote>Documents show the surgeons got the consent of three terminally ill patients with malignant brain tumors to introduce bacteria into their open head wounds, under the theory that postoperative infections might prolong their lives. Two of the patients developed sepsis and died, the university later determined.</blockquote> First, <blockquote>In 2008, the doctors proposed treating a glioblastoma patient with bacteria applied to an open wound to 'attack the tumor,' then later withholding antibiotics and letting the bacteria do its work.</blockquote> The FDA responded that animal studies would have to be done before any human research could be considered. Apparently the surgeons intended to do some animal research, but what they did, and what its results were remain unclear. Nevertheless, <blockquote>Between October 2010 and March 2011, the physicians went forward with three procedures on humans with malignant brain tumors, surgically introducing probiotics into their open head wounds.</blockquote> One surgeon did get <blockquote>IRB permission to move forward on Patient No. 1 with a 'one-time procedure' that was 'not associated with any research aim,' the letter states. University documents show that the physicians believed they had been given the go-ahead for all three surgeries, but officials later determined that they had been misinformed or were misunderstood by the doctors.</blockquote> No patient lived very long. Two developed sepsis before they died. After hearing that the surgeons were then planning to do the procedure on five more patients, <blockquote>The university threw on the brakes. On March 17, 2011, the IRB director ordered the doctors to immediately stop their probiotic treatments, according to university documents.</blockquote> I should point out that deliberately introducing bacteria into an otherwise sterile surgical site is a very radical and seemingly periolous step. Furthermore, a <a href="http://www.nature.com/news/can-bacteria-fight-brain-cancer-1.11080">blog post</a> in Nature News suggests that the reasoning used by the surgeons to support this approach was based on extremely weak evidence, <blockquote>researchers at the Catholic University of Rome examined the records of 197 patients treated for glioblastoma between 2001 and 2008, of which ten developed pathogenic infections after surgery. Those patients had a median survival rate of 30 months, whereas patients who did not become infected had a median survival rate of 16 months. However, the authors concluded that the association was 'not definitive'. [De Bonis, P. et al. Neurosurgery 69, 864–868 (2011). Link <a href="http://dx.doi.org/10.1227/NEU.0b013e318222adfa">here</a>. ] A 2009 report considered 382 patients with malignant brain cancer, 18 of whom developed infections. Infected patients lived longer on average, but the difference was not statistically significant. What’s more, the researchers reasoned that infection may correlate with longer survival not because infection prolongs survival but because patients who live longer are more likely to develop infections. [Bohman, L. E. et al. Neurosurgery 64, 828–834 (2009). Link <a href="http://dx.doi.org/10.1227/01.NEU.0000343525.89321.C5">here</a>. ]</blockquote> The University Investigation Then, <blockquote>The internal investigation began. Six months later, the university concluded its probe – ordering the doctors to halt all human research activity 'except as necessary to protect the safety and welfare of research participants.' In the case of Patient No. 1, the investigation found, ... [one surgeon] had made an 'incorrect statement' about restrictions on the bacteria's use, leading IRB staff to incorrectly conclude that such review was not necessary, Lewin told the FDA. As for Patients 2 and 3, the university found that treating them with an 'unapproved biologic' amounted to human-subjects research – and thus required prior review and approval.</blockquote> The junior neurosurgeon defended their conduct by claiming <blockquote>We believed that this was innovative treatment, not research, and that IRB approval was not needed</blockquote> The senior surgeon asserted that he <blockquote>believed the FDA gave its permission early on, if the doctors thought the treatment was 'beneficial to the patients.' He described the research ban as an "overreaction" by the university. 'And I understand it,' he said. There are people who blatantly break the rules that endanger all of their research programs. We certainly didn't blatantly trample any rules.'</blockquote> However, <blockquote>A renowned U.S. bioethicist, describing the alleged violations as 'a major penalty,' said the university's IRB was right to intervene – and quickly. Arthur Caplan, director of medical ethics at New York University's Langone Medical Center, said that desperate people are especially vulnerable and need added protections. 'If you're dying, you're kind of like reaching out to anything that anybody throws in front of you,' said Caplan</blockquote> Furthermore, per a Sacramento Bee <a href="http://www.sacbee.com/2012/07/28/4668495/uc-davis-neurosurgeon-department.html">follow-up article</a>, Elizabeth Woeckner, founder and director of Citizens for Responsible Care and Research, or CIRCARE, said the surgeons' "experiment" was <blockquote>the worst thing I've seen in my 12 years with CIRCARE</blockquote> An Overreaction, or an Under reaction? So far, this story seems different from many of those discussed on <a href="http://hcrenewal.blogspot.com/">Health Care Renewal</a>. The questionable conduct it describes, after all, appears to have resulted in serious negative consequences. Furthermore, it seems to have been conduct by two loose cannons, rather than to be a sign of systemic problems with leadership or governance. However, there is more to the story. First, the senior surgeon held a substantial leadership position at the time the events in question occurred. He is <blockquote>[Dr J Paul] Muizelaar, 65, who has been a department chairman at the School of Medicine since 1997</blockquote> He is pretty well paid, earning <blockquote>more than $800,000 a year as chairman of the department of neurological surgery</blockquote> In fact, a <a href="http://www.sacbee.com/2012/07/22/4648465/banned-ucd-doctor-is-one-of-ucs.html">companion article</a> in the Sacremento Bee noted, <blockquote>In 2010 – the same year Dr. J. Paul Muizelaar first performed an experimental treatment on a dying brain cancer patient at UC Davis Medical Center – the neurosurgeon made more money than 99.9 percent of all employees in the University of California system. With a total compensation package of $801,841 in 2010, he was the 35th highest earner, behind 27 other physicians, four athletic coaches and three executives, according to the most recent UC salary data.</blockquote> More importantly, even though the university's internal investigation was done in the fall of 2011, and at that time Dr Muizelaar was immediately banned from human research, he did not lose his leadership position. Instead, according to the first Sacramento Bee <a href="http://www.sacbee.com/2012/07/22/v-print/4648415/2-uc-davis-neurosurgeons-accused.html">article</a>, <blockquote>Despite the disciplinary action imposed last fall, Muizelaar was honored this spring with an additional academic role at UC Davis. He was named the first holder of the Julian R. Youmans endowed chair in the department of neurological surgery, according to an April 19 news release from the UCD School of Medicine.</blockquote> It is not the first time he has received special treatment. The <a href="http://www.sacbee.com/2012/07/22/4648465/banned-ucd-doctor-is-one-of-ucs.html">companion article </a>noted that Dr Muizelaar was able to attain and keep his position even though he never obtained a state medical license, <blockquote>Muizelaar, who previously was a professor of neurosurgery at Wayne State University in Detroit, was hired directly into the top post at UC Davis – even though he lacked a California medical license. A native of the Netherlands, where he was educated, Muizelaar was brought into the UC Davis School of Medicine under a 'special faculty permit' issued by the Medical Board of California. The provisional permit allows a foreign doctor who has been recognized as 'academically eminent' in a specific field to practice at a sponsoring California medical school and its formally affiliated hospitals. Currently, only 15 doctors at six of California's eight medical schools eligible to receive them hold special faculty permits.</blockquote> When asked why he never bothered to obtain a California medical license <blockquote>Muizelaar said he has not gotten a California license because he already works 80 to 100 hours a week and the step is 'not necessary.' 'I'll be frank with you, I'm world famous, so they gave me the license to practice here,' he said. 'I can go sit for the exams, but why would I do that?'</blockquote> Although Dr Muizelaar continued as department chair and in his endowed professorship for approximately 10 months after he was banned from human research, things happened fast after the stories appeared in the local media. Again <a href="http://www.sacbee.com/2012/07/25/4657366/uc-davis-chancellor-orders-review.html">according to</a> the Sacramento Bee, three days later, the CEO of the UC-Davis campus, Chancellor Linda P B Katehi <blockquote>ordered a top campus official to conduct a 'comprehensive review' of accusations that two university neurosurgeons conducted unauthorized research on dying brain cancer patients, as reported in Sunday's Bee. Ralph J. Hexter, the provost and executive vice chancellor, will lead another investigation into the actions of Dr. J. Paul Muizelaar, the longtime chairman of the department of neurological surgery, and his colleague, Dr. Rudolph J. Schrot, according to a university spokesman.</blockquote> A day after that, the Sacramento Bee <a href="http://www.sacbee.com/2012/07/28/4668495/uc-davis-neurosurgeon-department.html">reported</a>, <blockquote>A UC Davis neurosurgeon accused of performing unauthorized research on humans has 'temporarily relinquished' his position as chairman of the department of neurological surgery, the university confirmed Friday.</blockquote> However, do not expect to hear much more about this, <blockquote>A spokeswoman for UC Davis Health System said 'there will be no further system statement on this or other personnel actions.'</blockquote> Summary: A Culture of Unaccountable Leadership To sum up, the highly paid chair of neurosurgery at UC-Davis performed bizarre, and potentially dangerous experiments on three patients with terminal cancer, all of whom died, without obtaining permission from the institutional review board. After internal investigation, the chair was banned from performing further human research, but kept his well-paid position, and was given a new endowed professorship.  He only was forced to temporarily step down about nine months later, after reports of the affair appeared in the media.  So, a la George Orwelll's <a href="http://en.wikipedia.org/wiki/Animal_Farm">Animal Farm</a>, doctors may think themselves as equals, but doctors who are health care leaders are more equal than others. After conduct that would likely lead to the dismissal of more ordinary doctors, those who are also in high management positions may just collect more honors.  Then again, Dr Muizelaar considered himself to be "world famous," so why should be be expected to play by the rules under which the common folk labor? This story also suggests a more general culture of unaccountable leadership at University of California - Davis. Note that the Chancellor who let the neurosurgeon continue in his leadership role despite his strange research conduct and the consequent research ban has appeared in Health Care Renewal before. Specifically, she attained some notoriety last year after campus police who report to her pepper-sprayed unarmed and apparently non-violent students at her own institution who were protesting as part of the "occupy" movement at that time. (See post <a href="http://hcrenewal.blogspot.com/2012/04/will-uc-davis-chancellor-be-held.html">here</a>.) A later investigation of the incident blamed Chancellor Katehi and her subordinates for "poor decision making," and some editorialists concluded that she showed "incompetence," or worse. Yet Chancellor Katehi retains her top leadership position. We have discussed how leaders of other health care organizations are rarely held accountable for bad behavior by their organizations. At times, this bad behavior has been criminal, and the leaders' unaccountability has seemed more like <a href="http://hcrenewal.blogspot.com/search/label/impunity">impunity</a>.  This seems to parallel a larger phenomenon in society.  Increasingly the wealthy and powerful seem unrestricted by the rules that us common folk are expected to follow.  As Charles Fergusson famously <a href="http://www.nakedcapitalism.com/2011/02/matt-stoller-a-very-political-oscars-%E2%80%93-not-a-single-executive-has-gone-to-jail.html">noted</a> on receiving his Oscar, <blockquote>three years after a horrific financial crisis caused by massive fraud, not a single financial executive has gone to jail and that’s wrong</blockquote> Health care, particularly in the US, continues to be increasingly expensive and inaccessible, yet its quality appears increasingly dubious. True health care reform would hold health care leaders accountable for upholding the health care mission.

Another Story of Unaccountable Leadership from UC-Davis: "World Famous" Neurosurgeon Banned from Research, but Still Department Chair

The University of California - Davis just keeps supplying us with lessons about problems with leadership and governance in major health care...

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We have occasionally posted about the activities of for-profit contract research organizations (CROs). These are commercial entities that conduct human research, including clinical trials for pharmaceutical, biotechnology and device companies. More clinical research is being done by such CROs rather than by academic investigators. CROs seem to operate under the radar of most physicians, academics, and policy makers, but sometimes stories surface that raise questions about them. For example, we discussed the trials by SFBC International (now <a href="http://www.pharmanet.com/">PharmaNet Development Group</a>) in Miami that enrolled immigrants, often undocumented, under questionable circumstances and in Montreal that resulted in the transmission of active tuberculosis (see post <a href="http://hcrenewal.blogspot.com/2006/03/consequences-of-sfbc-internationals.html">here</a> and links backward); and the trial by <a href="http://www.parexel.com/">Parexel International </a>in London that put most of its subjects in intensive care (see post <a href="http://hcrenewal.blogspot.com/2006/08/parexel-blues-again.html">here</a>, with links backward). Last year, as we discussed <a href="http://hcrenewal.blogspot.com/2008/06/clinical-trials-torture-economy.html">here</a>, two articles questioning the ethics of research done under the auspices of CRO appeared in two major medical journals. In academia, human research is supposed to be overseen by institutional review boards (IRBs). Research done by CROs is also supposed to be overseen by IRBs, but the IRBs that do so are often also commercial. Despite concern that commercial IRBs may be tempted to lower their standards to get more business, commercial IRBs have flown even lower under the radar than have CROs. However, last week, a story appeared about how a "sting operation" tested one commercial IRB with amazing results. Here are excerpts from <a href="http://online.wsj.com/article/SB123811179572353181.html">the article by Alicia Mundy in the Wall Street Journal</a>, <blockquote> The sting, detailed at a House Energy and Commerce Committee hearing Thursday, involved the creation of a fictitious company and a fake medical device, a surgical adhesive gel. The sham firm then applied to three for-profit oversight groups -- called institutional review boards, or IRBs -- for approval to begin a clinical trial using their adhesive on human subjects. Two IRBs contacted by the GAO's sting operators -- Argus IRB of Arizona and Fox IRB of Illinois -- rejected the Adhesiabloc proposal because of unanswered safety questions. 'We realized it was a terrible risk for the patient … It is the worst thing I have ever seen,' an Argus IRB reviewer said, according to a slide shown at the hearing. <a href="http://www.coastirb.com/">Coast IRB </a>LLC of Colorado Springs, Colo., did approve a study for the fictitious adhesive gel, 'Adhesiabloc.' </blockquote> The GAO also ran an experiment to see if the US Department of Health and Human Services (DHHS)would register a truly dubious commercial IRB <blockquote> The committee, working with the Government Accountability Office, Congress's investigatory arm, named the CEO of the fake IRB Truper Dawg, after a staffer's three-legged dog, now deceased. Other fake names included 'April Phuls' and 'Timothy Wittless,' which lawmakers said should have signaled irregularities to HHS. The department registered the IRB. </blockquote> On one hand, these anecdotes suggest, along with the stories discussed above, that CROs and the commercial IRBs that are supposed to oversee them deserve further scrutiny. Beyond that, one wonders if it is good for society for human research, including experiments involving drugs and devices, to be done by commercial firms dependent for their income on the companies that make these drugs and devices, overseen by other commercial firms also dependent on these same companies. The fundamental conflict is embodied by <a href="http://www.coastirb.com/page.asp?id=2&name=About">Coast IRB's self-description</a>: <blockquote>as an advocate and a catalyst for an ever-stronger pharmaceutical industry, ethically and economically. </blockquote>which also <blockquote>recognizes the vital importance of our role in protecting individuals in all clinical studies and in continuously raising the bar on professional standards. </blockquote> How can the company be an "advocate" for the industry while simultaneously protecting the people exposed to the industry's still experimental drugs? See also <a href="http://www.gooznews.com/archives/001363.html">comments</a> on the GoozNews blog.

Sham Studies and the Commercial IRBs that Approve Them, and Sham IRBs and the Government Department that Registers Them

We have occasionally posted about the activities of for-profit contract research organizations (CROs). These are commercial entities that co...

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