healthy4u: AstraZeneca

Minimizing Legal Liability or Upholding the Mission? - the Markingson Case Redux

There are new, and troubling developments in the long running case of Dan Markingson, the psychiatric patient and research subject who committed suicide while enrolled in a trial of anti-psychotic drugs at the University of Minnesota nearly 10 years ago. Summary of the Case A good quick summary of this case just <a href="http://blogs.law.stanford.edu/lawandbiosciences/2013/03/14/the-markingson-case-investigate-the-university-of-minnesota/">appeared </a>in the Center for Law and Bioscience blob out of the Stanford Law School.  <blockquote class="tr_bq">Dan Markingson – a vulnerable, psychotic young man – was forced to choose between enrolling in a Pharma-funded drug study or being involuntarily committed (in other words, locked up).  A UMN [University of Minnesota]  doctor enrolled him in the study despite having just determined that Dan 'lack[ed] the capacity to make decisions regarding [his] treatment,' rendering it highly unlikely that Dan could have given valid informed consent to participate.  As Dan's mother, Mary Weiss, observed his mental condition deteriorating, she repeatedly tried to have Dan removed from the trial – at one point asking  'Do we have to wait until he kills himself or someone else before anyone does anything?'  But the UMN co-investigators in the drug study refused to terminate his participation.  Shortly after Ms. Weiss made her desperate plea, Dan Markingson killed himself by cutting his own throat.</blockquote> Our most recent (2011) post on the case was <a href="http://hcrenewal.blogspot.com/2011/02/university-of-minnesota-where-nothing.html">here</a>.  In it we also noted that there was reason to think: -  The design of the controlled trial was flawed. -  Financial conflicts of interests may have influenced the trial investigators' actions, particularly their questionable enrollment of Mr Markingson in the trial and their retention of him in it despite his apparent clinical deterioration. Despite that, when bioethicists and the University of Minnesota called for a new investigation of the trial and what happened to Mr Markingson, the university rebuffed them. Worse, as detailed in a 2012 <a href="http://blogs.law.stanford.edu/lawandbiosciences/2012/12/14/how-not-to-run-a-drug-study-the-university-of-minnesota-puts-on-a-clinic/">post</a> in the Center for Law and Bioscience blog, not only did university officials rebuff this call, but the university general counsel, who had been operating at the heart of this case, appeared to threaten the leading bioethicist dissident, Dr Carl Elliott: <blockquote class="tr_bq"> After Carl Elliott, the University of Minnesota bioethicist, refused to drop the matter, Rotenberg asked the university’s Academic Freedom and Tenure Committee to take up the question of '[w]hat is the faculty[’s] collective role in addressing factually incorrect attacks on particular university faculty research activities?' – a question that appeared both to accuse Elliott of 'factually incorrect attacks' and to call for some unspecified action to 'address' them.  Other faculty, including the president of the Minnesota chapter of the American Association of University Professors, viewed this as an attempt to intimidate Elliott into silence.  If so, it backfired.  The story <a href="http://goo.gl/4BIuM">ended up in the press</a>, putting the Markingson case back in the public eye and once again making the University of Minnesota look really bad.</blockquote> New Evidence Unearthed In 2013, Dr Elliott made public what may be important new evidence in the case.  As <a href="http://www.startribune.com/local/193447511.html">summarized</a> by the Minneapolis Star-Tribune, <blockquote class="tr_bq">The professor, Carl Elliott, says he has obtained consent documents for two separate schizophrenic patients that appear to be exact copies — not just in the subjects’ apparent replies, but in the positions of the lettering on the pages. Elliott said it is improbable that separate patients would provide identical responses to the questionnaire, which includes open-ended questions about the risks and requirements of clinical research. And that, he said, raises questions about whether the university was really examining patients to determine their ability to consent to research.</blockquote>  One crucial question about the case is how a patient who was actively psychotic - out of touch with reality - could give true informed consent to participation in a drug trial.  These new documents suggest major irregularities in the process used in the trial to assure that patients did give informed consent.  Furthermore, as <a href="http://www.mndaily.com/news/campus/2013/03/14/10-years-study-scandal-lives">reported</a> by the Minnesota Daily, other documents that Dr Elliott found suggested problems with records that related to whether study investigators would have had legal authority to access Mr Markingson's medical records, also suggesting major problems with trial administration.  These documents, unknown until recently, suggest new concerns with how the study in which Mr Markingson was enrolled, and during which he died, was run.  Yet, the University of Minnesota's official response to them, once again orchestrated by university counsel Mark Rotenberg, attacked the legitimacy of the documents (and indirectly, attacked Prof Elliott again), as reported by the Star-Tribune, <blockquote class="tr_bq">the university’s general counsel, Mark Rotenberg, challenged the authenticity of the documents and disagreed that study recruiters failed to obtain proper and independent consent from mentally ill patients. 'I am challenging these allegations directly,' he said. 'We have no reason to believe the consent forms were prepared inappropriately.'</blockquote> As Matt Lamkin <a href="http://blogs.law.stanford.edu/lawandbiosciences/2013/03/14/the-markingson-case-investigate-the-university-of-minnesota/">wrote</a> in the Stanford Law and Bioscience blog,  the University's responses all through this case have been focused  not on the welfare of patients, maintaining the trust of research participants, or the integrity of clinical trials, but on the legal defense of  the University and its leaders <blockquote class="tr_bq">Despite all this (<a href="http://blogs.law.stanford.edu/lawandbiosciences/2012/12/14/how-not-to-run-a-drug-study-the-university-of-minnesota-puts-on-a-clinic/">and much more</a>), the University has never acknowledged any errors or taken any disciplinary action related to the Markingson case and has repeatedly rejected calls for an independent investigation.  That’s probably because from the start the University has handled this case as a litigation matter.  Rather than trying to determine whether there were problems with the way its personnel treated Markingson, the University has focused on minimizing its potential liability.  Accordingly, the University appears to run every inquiry related to the case through the office of its General Counsel, Mr. Rotenberg.  When Carl Elliott (my mentor as a grad student at UMN) wrote <a href="http://www.motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca">a damning article about the case</a> in Mother Jones, the University’s response came from Rotenberg.  When <a href="http://www.scribd.com/doc/49659724/U-of-M-Board-of-Regents-Markingson-Letter">UMN bioethicists called on the University’s Board of Regents to launch an independent investigation</a>, the Regents deferred to Rotenberg.  Not surprisingly, he declined. When you turn to your lawyer, you’re going to get a particular kind of response.  The GC isn’t in a position to take an objective look at the circumstances.  He’s an advocate.  His role is not to make sure the client has conducted itself ethically, but to minimize the client’s risk.  Asking your lawyer to respond to allegations of wrongdoing is like asking your PR flacks to do so.  Their job is to make their clients look good, not to make sure they’ve acted properly.</blockquote>Note that this still begs the question of who the client is.  Is it the university, or the university's leaders? Furthermore, as Mr Lamkin pointed out, the general counsel would appear to have a conflict of interest.  It may be he has an interest in defending his own actions, as well as those of his client(s), whether they are the university, its leaders, or both.  <blockquote class="tr_bq">In addition to Mr. Rotenberg’s role as the University’s top defender and advocate, there is another reason he cannot impartially consider requests for an investigation: the General Counsel’s Office is an important player in some of the disturbing events at issue.  As noted above, Rotenberg himself has been accused of attempting to intimidate and silence the bioethicist who has most doggedly sought an investigation.  The University’s lawyers are also responsible for the disgraceful silencing of Markingson’s mother, Mary Weiss.  After avoiding liability by arguing the University was immune from suit, these lawyers then threatened to force Weiss – whose son had died in a University doctor’s 'care – <a href="http://blogs.law.stanford.edu/lawandbiosciences/2011/09/15/academic-health-centers-bare-knuckled-litigation-tactics/">to pay the University’s legal costs</a> of some $57,000.  The University used that threat as leverage to get Weiss to forgo an appeal of the trial court’s decision.</blockquote> So as the University continues to refuse any new consideration of this this seemingly never-ending case, Dr Elliott has posted an <a href="https://www.change.org/petitions/governor-mark-dayton-of-minnesota-investigate-psychiatric-research-misconduct-at-the-university-of-minnesota-2">online petition</a> calling for an outside investigation.   We will see how Mr Rotenberg reacts to this. Summary A very troubling aspect of this case is that it has shown that the university leadership has seemed to care, at best, more about fending off litigation than upholding the university's mission.  The mission of the university is supposed to be discovering and disseminating the truth in a spirit of free inquiry.  Added to the mission of medical schools and university teaching hospitals is taking good care of patients, and putting the patients' interests ahead of all other concerns.  Yet, in this case, university leaders have not seemed to care whether in their haste to push back legal liability they were stepping on their faculty's academic freedom and free speech, the integrity of the medical research done at the university, and most importantly the rights of their patients and research subjects.  Furthermore, it is not clear whether they mainly feared the impact of litigation on the university, or how litigation might actually end up holding them accountable. As Dr Judy Stone <a href="http://blogs.scientificamerican.com/molecules-to-medicine/2013/03/12/a-clinical-trial-and-suicide-leave-many-questions-part-5-the-case-of-the-mysteriously-appearing-documents/">wrote</a> in her Scientific American blog, <blockquote class="tr_bq">  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.</blockquote> Again, note that UMN cannot itself believe or protect.  People acting ostensibly on its behalf may have been protecting themselves from scandal, and believing that the size and status of their institution gave them, the leaders, impunity. The case of Mr Dan Markingson is a continuing reminder that to reform health care, health care organizations need to be lead by people who put the health care mission first and are willing to be accountable for that mission.   I hope that eventually there is an honest investigation of this case, and a commitment to reform based on its conclusions. See additional thoughts from Dr Howard Brody <a href="http://brodyhooked.blogspot.com/2013/03/latest-on-markingson-case-at-u-minn.html">on the Hooked: Ethics, Medicine and Pharma blog</a>, on the <a href="http://1boringoldman.com/index.php/2013/03/13/intrinsically-flawed-and-dangerous/">1BoringOldMan blog</a>, <a href="http://ptable.blogspot.com/2013/03/online-petition-requesting-governor.html">on the Periodic Table blog</a>, and last but certainly not least, many comments by Dr Carl Elliott on the <a href="http://loathingbioethics.blogspot.com/">Fear and Loathing in Bioethics blog.  </a>

Minimizing Legal Liability or Upholding the Mission? - the Markingson Case Redux

There are new, and troubling developments in the long running case of Dan Markingson, the psychiatric patient and research subject who commi...

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"I'm Not Here to Sell Drugs" - Then Why Use Company Provided "Correct" Slides?

In October, 2010, we <a href="http://hcrenewal.blogspot.com/2010/10/not-best-and-brightest-drug-marketers.html">discussed</a> a series of reports by Pro Publica and multiple other respected news organizations about payments by seven pharmaceutical companies to thousands of doctors.  Industry often claims that they only pay the best and the brightest physicians and academics to provide education relevant to their products.  However, the ProPublica et al report suggested that they mainly recruited physicians who already showed their favor to their products by prescribing them often, but soothed their consciences by dubbing them "thought leaders" or "key opinion leaders."  While some of the physicians were well-known academics, others had notably blemished records.  Since then, news media around the US have looked into interactions among local physicians and academic medical institutions and the seven pharmaceutical companies.  In November, 2010, <a href="http://hcrenewal.blogspot.com/2010/11/of-drug-talks-deception-and-denial.html">here</a> we discussed cases that suggested that pharmaceutical companies like physician speakers because they are more "believable" than pharmaceutical representatives, and choose physicians who already are prolific prescribers of the drug to be promoted, and that suggested that some physicians realized that speaking for pharmaceutical companies influenced their own prescribing. Since then, more investigations of local physicians' interactions with pharmaceutical companies have appeared that reinforced contrasts between rationalizations that physicians and drug companies use to support continued payments for "drug talks," and what these talks are really about. "Leaders in Their Field" vs Sanctions and Crimes  Many pharmaceutical (and other health care corporations) have repeated the mantra that the physicians they hire to give talks are the best and the brightest.  The physicians who give the talks sometimes get to believe this.  For example, a ProPublica follow-up report[1] on discrepancies between data the pharmaceutical companies put on the web and gave to state regulators noted: <blockquote>Pfizer, for example, told the state it paid Dr. Randy Schapiro $1,770 last year. But on the firm’s website, it reported spending $43,827 on him in the second half of 2009 alone.</blockquote>It then quoted Dr Schapiro: <blockquote>Schapiro said the doctors paid by pharmaceutical companies are 'leaders in their fields,' and patients should want to see their physician among them. 'If their doctor is not on the list,' he said, 'maybe they should look for a different doctor.'</blockquote> On the other hand, several of the local news articles focused on physicians who were paid drug company speakers despite having chequered backgrounds, shall we say. In the Elmira Star Gazette[2]: <blockquote>Tulio Ortega, a Rochester psychiatrist who made $144,548 from Eli Lilly and AstraZeneca for speaking to groups of peers during the last two years - was put of [sic] probation for two years in 2008 and ordered to pay a $7,500 fine after being sanctioned for negligence and incompetence.</blockquote>Also, <blockquote>Lilly also paid Yonkers physician Ali Sherzoy $4,334 in the first two quarter of this year, even though he had his license suspended in New York and New Jersey earlier this year after pleading guilty to a count of criminal sexual contact in 2008. Sherzoy told ProPublica the incident involted his family's nanny and had nothing to do with his ability to practice medicine. Other New York doctors were sanctioned for incidents ranging from deficiencies in handling controlled substances to being convicted of tax evasion.</blockquote> Another article by the same author[3] noted two more cases: <blockquote>In 1991, Johnson City doctor Louis Mateya was charged with professional misconduct after a 22-year-old woman accused him of unzipping his pants and fondling himself during an examination. Mateya admitted guilt to the charge. The State Board for Professional Medical Conduct suspended his license for two months, followed by a 58-month probationary period, during which he was monitored by a psychiatrist and a health professional selected by the board. During the last nine months of 2009, GlaxoSmithKline paid Mateya, an internist at United Health Services, $1,750 to speak on behalf of Lovaza, Glaxo's prescription omega 3 fish oil, according to an e-mail from a United Health Services spokeswoman.</blockquote> Also, <blockquote>A second Southern Tier physician, Robert Douenias, of Corning, was also paid by Glaxo: $20,000 during the same time frame to deliver speeches, even though he received sanctions in 1992. According to the Office for Professional Medical Conduct (OPMC) records, Douenias lied about a previous criminal conviction on his application for a New York medical license. He received a censure and reprimand from the OPMC, was ordered to perform 200 hours of public service and was placed on probation for two years. Douenias said on his application he had never been convicted of a crime in any state or country, even though he had a previous conviction, according to OPMC records.</blockquote> Note that the original ProPublica reporting from their database emphasized cases of physicians paid to speak by pharmaceutical companies who also had been sanctioned by medical boards or the criminal justice system (see post <a href="http://hcrenewal.blogspot.com/2010/10/not-best-and-brightest-drug-marketers.html">here</a>). Although drug marketers like to tell physicians they are selected as "thought leaders" because of their brilliance, it appears that the selection of such "key opinion leaders" is not necessarily based on sterling character. "I'm Not There to Sell a Drug," But Then Why Use the Company's Slides? A number of the reports featured physicians who asserted their independence, at least from marketing goals.  For example, as reported by the Duluth (MN) News Tribune[4], <blockquote>A Duluth psychiatrist has received more than $525,000 since 2002 in payments from pharmaceutical companies, far more than any other Northland doctor, an analysis by the News Tribune shows. Dr. Tracy Tomac of St. Luke’s hospital was paid by the companies to give presentations on health and drug issues.</blockquote> Furthermore, <blockquote>'I’m there as an educator and resource,' she said. 'I’m not in business to do a sales pitch. I’m not a salesperson.'</blockquote> Also, <blockquote>In 2007, [Dr] Tomac said her presentations included content that was screened and approved by the FDA,....</blockquote> However, other reporting suggested that content "screened and approved by the FDA" was content provided by the pharmaceutical companies. For example, The Tennessean noted[5]: <blockquote>Dr. Jan Brandes heads the Nashville Neuroscience Group, a clinic that's now part of Nashville-based Saint Thomas Health Services. She made $111,150 in outside income over the past two years, largely in speaker fees paid by drug company GlaxoSmithKline, which markets a wide array of brand-name drugs, literally from A to Z.</blockquote> Dr Brandes also asserted, <blockquote>'The real point is I'm not there to sell a drug,' Brandes said. 'I'm there to interpret trial results, talk about disease states and help physicians understand where this research might fit in the context of their practice.'</blockquote> However, <blockquote>Most drug companies now require physicians to use the company's slides and presentations if they pay them to speak at an event. The industry says that is to ensure that all U.S. Food and Drug Administration rules are met and that physicians don't wander off into discussing uses for a particular product that haven't been approved by regulators.</blockquote> Also, an article in the Alexandria (VA) Gazette Packet[6] noted: <blockquote>Whistleblower lawsuits filed in recent years have accused firms of using doctors to push pills for unapproved uses during dinnertime talks, prompting at least 10 firms to settle cases for nearly $7 billion in the last three years. Since that time, pharmaceutical companies have tightened control over what happens during presentations given on their dime. Last year, for example, GlaxoSmithKline instituted a new policy prohibiting doctors from using their own slides during presentations. Starting in 2010, all doctors giving speeches sponsored by GlaxoSmithKline must use slides presented by the pharmaceutical company in the order specified. 'We want to make sure that everything is correct,' said Mary Anne Rhyne, a spokeswoman for GlaxoSmithKline. 'The best way to do that is to have our team prepare the slide.'</blockquote>Note that Dr Brandes above was paid mainly by GlaxoSmithKline, who presumably also provided all her slides and made sure that everything she said was "correct," at least in terms of what GlaxoSmithKline thought was correct. And one more example per MyFoxAtlanta[7]: <blockquote>Some of Georgia's highest paid physicians? .... and Roswell psychiatrist Dr. Michael Banov: over $68,000, also from Lilly.</blockquote>Dr Banov asserted: <blockquote>We don't sell medications. We simply educate physicians about data, and they make their own mind up.</blockquote>However, <blockquote>Banov says, the drug company - not him - creates the materials used in his speeches, and he says there's a reason for that. 'We are only able to present the data. We're not able to present our personal opinions. Our personal preferences, how we use the medication off label. any of that. So we're held to a very tight standard by the FDA,' said Banov.</blockquote>Drug companies may say they make their paid physician speakers use slides provided by the company to prevent them from talking about "off-label" uses.  However, there is no reason for a physician-educator not to talk about "off-label" uses, and physicians can prescribe any legal drug for whatever purpose they see fit, whether or not the drug is on or "off label."  But drug companies are prohibited by law from promoting off-label uses.  Requiring physicians to use drug companies' slides and preventing them from talking about "off-label" uses demonstrates that the physicians are functioning as marketers, not educators.  Summary As local reporters look into more cases, it becomes increasingly clear that up to now, pharmaceutical companies have been none too fussy about which physicians they pay to speak about their products. It is self-serving, but inaccurate for both sets of parties to assert that the companies choose only the "best and the brightest."  Furthermore, it has now become glaringly obvious that the purpose of "drug talks" is, well, to sell drugs.  Some physicians paid by drug companies to speak may bluster about their independence, but if they are using company provided slides, who can deny they are influenced  by the company.  Furthermore, when companies insist not merely on providing slides, but on ensuring that "everything is correct," then it is clear that it is the companies' talks that the physicians are giving.  Physicians giving company talks cannot be speaking independently, and hence must be regarded as company sales personnel, whose disguises as independent doctors or medical academics are now in tatters. Doctors who still choose to go to "drug talks" should have no illusions that they are being exposed to anything other than marketing.  Thus, I urge my colleagues to forgo the nice meals and the company prepared "correct" slides, and spend the time trying to more critically assess the clinical evidence.  References 1.  Ornstein C, Weber T. In Minnesota, drug company reports of payments to doctors arrive riddled with mistakes.  ProPublica, Dec 10, 2010.  Link <a href="http://www.propublica.org/article/in-minnesota-drug-company-reports-of-payments-to-doctors-mistaken">here</a>. 2. Hunter J. Rochester psychiatrist, sanctioned for incompetence, made $144K from drug companies. Elmira Star-Gazette, Dec 4, 2010. 3. Hunter J. Despite sanctions, physicians hired as drug company pitchmen. PressConnects.com, Dec 4, 2010. Link <a href="http://www.pressconnects.com/article/20101204/NEWS01/12040345/Despite-sanctions-physicians-hired-as-drug-company-pitchmen">here</a>. 4. Stahl B. Duluth doctor denies payments from drug companies sway decisions.  Duluth News Tribune, Dec 20, 2010.  Link <a href="http://www.duluthnewstribune.com/event/article/id/186841/">here</a>. 5. Ward G. They say they prescribe based on patients, not Big Pharma. Tennessean, Dec 19, 2010. Link <a href="http://www.tennessean.com/article/20101219/BUSINESS01/12190355/TN-doctors-get-big-bucks-from-drugmakers">here</a>. 6. Pope ML. Conflict of interest? - Alexandria doctors receive thousands of dollars from Big Pharma.  Alexandia Gazette Packet, Jan 13, 2010.  Link <a href="http://www.connectionnewspapers.com/article.asp?article=347442&paper=59&cat=104">here</a>. 7. Galvin B. Health watch: doctors and drug companies. MyFoxAtlanta, Dec 29, 2010. Link <a href="http://www.myfoxatlanta.com/dpp/health/Health-Watch%3A-Doctors-and-Drug-Companies-20101229-gda-sd">here</a>.

"I'm Not Here to Sell Drugs" - Then Why Use Company Provided "Correct" Slides?

In October, 2010, we discussed a series of reports by Pro Publica and multiple other respected news organizations about payments by seven p...

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Sunday Settlement and Guilty Plea Roundup

Here we go again.  AstraZeneca / Seroquel We have posted frequently about allegations of devious marketing techniques used by AstraZeneca to promote its blockbuster atypical anti-psychotic drug Seroquel (quetiapine.)  See our posts <a href="http://hcrenewal.blogspot.com/2009/02/buried-data-smoke-and-mirrors-job-and.html">here</a>, <a href="http://hcrenewal.blogspot.com/2009/03/blogscan-over-selling-of-seroquel.html">here</a>, <a href="http://hcrenewal.blogspot.com/2009/05/more-documents-about-selling-of.html">here</a>, <a href="http://hcrenewal.blogspot.com/2009/10/more-on-misleading-promotion-of.html">here</a>, and <a href="http://hcrenewal.blogspot.com/2009/10/nemeroff-seroquel-and-accme.html">here</a>.  Now, as <a href="http://www.nytimes.com/2010/04/28/business/28drug.html">reported</a> by the New York Times, it is time for AZ to settle with the US government. <blockquote>AstraZeneca has completed a deal to pay $520 million to settle federal investigations into marketing practices for its blockbuster schizophrenia drug, Seroquel, the Attorney General, Eric Holder, said at a news conference Tuesday afternoon. 'AstraZeneca paid kickbacks to doctors as part of an illegal scheme to market drugs for unapproved uses,' Kathleen Sebelius, secretary of health and human services, said at the event in Washington. She said the company promoted drugs for unapproved uses by children, the elderly, veterans and prisoners. AstraZeneca agreed to sign a corporate integrity agreement with the federal government over its marketing of Seroquel for unapproved uses, but will not face criminal charges, company and federal officials said. The company, based in London, has been accused of misleading doctors and patients by playing up favorable research and not adequately disclosing studies that show Seroquel increases the risk of diabetes. </blockquote> Of course, an AZ spokesperson had a different take on it. <blockquote>Glenn Engelmann, AstraZeneca’s U.S. general counsel, released a statement saying the company denies the allegations but settled the investigation with the payment. 'It is in the best interest of AstraZeneca to resolve these matters and to move forward with our business of discovering and developing important, life-changing medicines — while avoiding the delay, uncertainty, and expense of protracted litigation,' Mr. Engelmann said. </blockquote> Johnson and Johnson / Topamax On the other hand, the issue of how Johnson and Johnson marketed Topamax (topiramate), a drug approved for treating seizures, is a new one for Health Care Renewal.  Here is the story, <a href="http://www.businessweek.com/news/2010-04-29/j-j-to-pay-81-million-end-federal-cases-on-topamax-update2-.html">via Bloomberg</a>. <blockquote>Two units of Johnson & Johnson will pay more than $81 million to resolve criminal and civil claims over illegal promotion of the epilepsy drug Topamax, the U.S. Justice Department said. Ortho-McNeil Pharmaceutical LLC agreed to plead guilty to a misdemeanor and pay a $6.14 million criminal fine for misbranding the drug, the government said. Ortho-McNeil-Janssen Pharmaceuticals also will pay $75.37 million to resolve civil allegations that it illegally marketed Topamax and caused false claims to be submitted to government health programs. While the Food and Drug Administration approved Topamax for the treatment of partial onset seizures, Ortho-McNeil Pharmaceutical promoted the drug for unapproved psychiatric uses, the government said. The company hired physicians through its 'Doctor-for-a-Day' program to join sales representatives in visiting doctors and to speak to colleagues about unapproved uses and doses, according to the government.</blockquote> In this case, the company admitted wrong-doing as part of the specific plea agreement. <blockquote>Under the plea agreement, Ortho-McNeil Pharmaceutical will admit that from 2001 to 2003 it promoted Topamax 'for certain uses not approved' by the FDA, according to a statement by Ortho-McNeil-Janssen. The company 'voluntarily discontinued the program at issue before receiving the government’s first subpoena in the investigation,' according to the statement. Ortho-McNeil-Janssen also will sign a five-year corporate integrity agreement with the U.S. Health and Human Services Department. </blockquote> Summary Once more, with feeling ....  We have discussed a series of <a href="http://hcrenewal.blogspot.com/search/label/legal%20settlements">legal settlements</a> and <a href="http://hcrenewal.blogspot.com/search/label/crime">criminal convictions</a> and guilty pleas resolving cases of alleged wrong-doing by health care organizations. Almost none included any penalties for people who authorized, directed or implemented the bad behavior. None of the financial penalties were so big as to be more than another cost of doing business for the organizations involved. Corporate entities, but very rarely people have pleaded guilty or been convicted (almost always of misdemeanors), Some of the cases included gimmicks, like a subsidiary constructed only to plead guilty, that otherwise seemed to lessen accountability. If we truly want health care that is accessible, of high quality, at a fair price, and more importantly, if we want health care that is honest and focused on patients, we need to provide health care leaders with clear, rational incentives in these directions, and make them fully accountable for their actions, and the courses of their organizations under their leadership. ADDENDUM (2 May,2010) - See also <a href="http://brodyhooked.blogspot.com/2010/04/cost-of-doing-business-same-song-83rd.html">comments </a>on the Hooked: Ethics, Medicine, and Pharma blog by Dr Howard Brody on the AZ settlement.

Sunday Settlement and Guilty Plea Roundup

Here we go again. AstraZeneca / Seroquel We have posted frequently about allegations of devious marketing techniques used by AstraZeneca to...

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AstraZeneca Settles

Here is the latest in the parade of legal settlements of cases of alleged wrong-doing by health care organizations.  As reported <a href="http://www.nytimes.com/2009/10/30/business/30drug.html">by Duff Wilson in the New York Times</a>, <blockquote>The pharmaceutical company AstraZeneca said Thursday that it had reached a $520 million agreement to settle two federal investigations and two whistle-blower lawsuits over the sale and marketing of its blockbuster psychiatric drug Seroquel. One of the investigations related to 'selected physicians who participated in clinical trials involving Seroquel,' AstraZeneca disclosed in a government filing. The other case related to off-label promotion of the drug. Seroquel was the top-selling antipsychotic drug in America. It had $17 billion in sales in the United States since 2004, according to IMS Health, a research firm. Tony Jewell, a company spokesman, declined to be more specific about the physicians or clinical trials under investigation. He said the company was in final negotiations to settle the whistle-blower suits and reach a corporate integrity agreement with the Justice Department. The name of the whistle-blowers and other details of the suits remained sealed in federal court. Stephen A. Sheller, a lawyer in Philadelphia for the whistle-blowers, and Patricia Hartman, a spokeswoman for the United States attorney in Philadelphia, both declined to comment. </blockquote> Here we go again. As the Times article noted, <blockquote>AstraZeneca, based in Britain, joins a list of drug makers that have paid billions to settle inquiries initiated by complaints from former company insiders. Earlier this year, Eli Lilly & Company paid $1.4 billion over its marketing of Zyprexa, another antipsychotic drug. And Pfizer announced it would pay $2.3 billion, including a record $1.195 billion criminal fine, mostly over its painkiller Bextra, which has been withdrawn from the market. </blockquote> Does anyone really still believe that integrity agreements, and settlements assessed against huge corporations deter such profitable bad behavior? A half a billion dollar one-time settlement is just a small cost of doing business for a company that sold $17 billion worth of the offending drug in the last five years. As in the case of many other previously announced <a href="http://hcrenewal.blogspot.com/search/label/legal%20settlements">settlements</a>, it appears that nobody who authorized, directed, or implemented the bad behavior that led to the settlement will suffer any sort of negative consequences. We previously discussed allegations that AstraZeneca manipulated and suppressed clinical research, and organized deceptive marketing campaigns in support of Seroquel sales (<a href="http://hcrenewal.blogspot.com/2009/10/more-on-misleading-promotion-of.html">here</a>, and <a href="http://hcrenewal.blogspot.com/2009/10/nemeroff-seroquel-and-accme.html">here</a>).  If we do not discourage such practices, they will continue to bias the clinical evidence making expensive drugs and devices seem more effective and less dangerous than they really are.  Is it any wonder that we over-use and over-pay for these products?  Anyone seriously interested in reforming health care to improve quality and access while moderating costs ought to pay attention to behavior that leads to such over-use and over-payment.  (However, there may be hope.  Perhaps in the future there will be more effective deterrence.  A recent indictment named not only the device company Stryker Biotech (a subsidiary of Stryker Corporation), but also its former CEO and three managers.)

AstraZeneca Settles

Here is the latest in the parade of legal settlements of cases of alleged wrong-doing by health care organizations. As reported by Duff Wil...

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Nemeroff, Seroquel, and ACCME

Nemeroff, Seroquel, and ACCME Roy Poses has <a href="http://hcrenewal.blogspot.com/2009/10/more-on-misleading-promotion-of.html">discussed</a> the atypical antipsychotic drug Seroquel (quetiapine) several times on this site, pointing out manipulation of clinical research results to enhance the appearance of efficacy, and suppression of studies with unfavorable results. I call this augmenting the marketed profile of the drug. Daniel Carlat has commented on published Seroquel data <a href="http://carlatpsychiatry.blogspot.com/2009/06/geodon-ineffective-for-bipolar.html">here</a> and ClinPsych <a href="http://clinpsyc.blogspot.com/search?q=Seroquel">here</a>. AstraZeneca, the marketer of Seroquel, has also been busy with continuing medical education (CME) programs that augment Seroquel’s profile. Last December 8, one such program went on line, aired by the provider CME Outfitters. The program’s title was “Atypical Antipsychotics in Major Depressive Disorder: When Current Treatments Are Not Enough.” The corporate logo for CME Outfitters is Education with Integrity. I will allow readers to decide if the company is meeting its mission statement in this respect. The key opinion leader engaged by CME Outfitters to discuss Seroquel and other atypical antipsychotic drugs was Charles Nemeroff of Emory University. He was joined by 2 KOLs-in-training, whom I will not name. The corporate sponsor that paid CME Outfitters and, indirectly, these presenters was AstraZeneca. I do not need to rehearse here the ethical issues that have surrounded Dr. Nemeroff for the past several years. Suffice it to say that, as a result of those issues, Dr. Nemeroff is no longer chair of the department of psychiatry at Emory University, he is no longer editor-in-chief of the ACNP journal Neuropsychopharmacology, he was removed from involvement with ongoing federally funded research grants at Emory University, and he was put on a short leash by the Emory administration. On December 23, 2008 I filed a formal complaint about Dr. Nemeroff’s program with ACCME. My bill of particulars was lengthy, detailed, and backed up by extensive materials. In due course, ACCME investigated the complaint and found that the program did violate ACCME standards. With respect to content, ACCME determined that Dr. Nemeroff’s program lacked sufficient information about possible adverse effects of treatment with atypical antipsychotic drugs; and failed to emphasize sufficiently the efficacy of alternative treatments. With respect to commercial bias, ACCME determined that bias existed as a result of the absence of contrasting therapy data, and through downplaying the drawbacks related to treatment with atypical antipsychotic drugs in depressed patients. Following these findings by ACCME, the provider was notified of the violations in early September 2009, and the program was removed from the provider’s website. The sanitized statement of violations determined by ACCME does not capture the nuances of deceit, ineptitude, and deficient educational content in Dr. Nemeroff’s program. One remarkable example was Dr. Nemeroff’s citation of data, from one of his own publications, that were previously retracted. Did he think no one would notice? A second example involved biased presentation of the sponsor’s data for Seroquel. Two doses of Seroquel (150 mg and 300 mg) were tested. Only the results for the 300 mg dose were statistically significant. Nevertheless, in the video presentation one of the junior presenters stated very clearly that there was “significant improvement in both response and remission with both doses” of Seroquel. That is a falsification of the scientific record. That falsification does not meet ACCME requirements for fair, balanced, truthful, and honest teaching. As moderator, Dr. Nemeroff was required to correct this false statement made by his junior assistant, but Dr. Nemeroff failed to do so. The negative findings and sanction by ACCME against Dr. Nemeroff’s program are welcome, though I have to say it took ACCME an inordinately long time to complete their work. I also presented ACCME with several follow-on questions, which the Council is now considering. These are: • Did ACCME notify the presenters that their program violated ACCME policies? If not, why not? • Will CME credits be clawed back from physicians and other professionals who obtained credits through the noncompliant program? If not, why not? I believe this would be an effective form of negative feedback to the provider and the presenters. • Does ACCME have a process to require the provider and presenters to ascertain whether any patients were injured as a result of the violations that created biased and deficient information in this program? If not, why not? • Does ACCME require the provider to notify physicians and other professionals who completed the noncompliant program that the provider was sanctioned for violation of ACCME standards? If not, why not? • Does ACCME require the provider to furnish corrective materials to such professionals in order to remedy the bias and incompetence to which they were subjected through violation of ACCME standards, and thereby to remove potential danger to future patients? If not, why not? • Why did ACCME allow the noncompliant program to remain available long after the complaint was filed? I suggest that ACCME needs to place a hold on programs that are subject to active complaint. Had such a policy been in effect in December 2008, the violating program would not have been re-aired by the provider in early 2009, it would not have remained on-line for 9 months, and the damage to the continuing education community would have been contained. • Will ACCME issue a public listing of sanctions it has enforced against providers and presenters? If not, why not? State medical boards do exactly that in relation to physicians and other professionals who violate standards of practice. • Finally, I reminded ACCME that its primary constituents are patients, physicians and other professionals, not commercial or academic CME providers. It seems to me that ACCME was altogether too laissez-faire and dilatory in the way it handled this matter. At the time of my initial complaint last December, I requested expedited review precisely because additional airings of this violating program were scheduled. The good news is that ACCME seems to have got the message that things need to change. As one of their officers wrote to me recently, “We sincerely appreciate the time and effort you have put into participating in our complaints and inquiries process. You have raised important issues that the ACCME will review and address.” I await their next communications on the remaining questions. As for Dr. Nemeroff, he is yesterday’s news. The adverse findings by ACCME about his program serve as a reminder to corporate sponsors and CME companies that Dr. Nemeroff is so compromised by now that he has lost effectiveness as a front man for Pharma. Indeed, he is so toxic that he now glows in the dark.

Nemeroff, Seroquel, and ACCME

Nemeroff, Seroquel, and ACCME Roy Poses has discussed the atypical antipsychotic drug Seroquel (quetiapine) several times on this site, poi...

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More on the Misleading Promotion of Seroquel

Previous posts (<a href="http://hcrenewal.blogspot.com/2009/02/buried-data-smoke-and-mirrors-job-and.html">here</a> and <a href="http://hcrenewal.blogspot.com/2009/05/more-documents-about-selling-of.html">here</a>) noted internal documents from AstraZeneca made public during litigation about its blockbuster atypical antipsychotic drug Seroquel (quetiapine) suggesting that the company's marketers manipulated clinical research results to make them appear more favorable to the product, and suppress studies with unfavorable results that could not be easily manipulated. This week, <a href="http://www.bloomberg.com/apps/news?pid=20601085&sid=aplfa8pUrUsM">Bloomberg News reported </a>testimony from one trial about other aspects of Seroquel's marketing. The marketers' claims were at odds with the company's own research results: <blockquote> AstraZeneca Plc advised its sales force to promote the antipsychotic drug Seroquel as 'weight neutral' four years after company research found 'clinically significant' weight gains in users, internal documents show. AstraZeneca’s 'global strategy is to demonstrate to consumers that Seroquel has a weight-neutral profile,' Debbie Holdsworth, a marketing official, wrote in a 'dear colleague' letter dated May 14, 2001. The document was produced during a pretrial examination of former executive John Patterson. 'If 45 percent of patients gained significant weight in a year, how could that be weight-neutral?' patient attorney Ed Blizzard asked Patterson, citing a internal 1997 e-mail written by an AstraZeneca doctor, at a hearing in Orlando Oct. 5. </blockquote>Also, evidence was presented that suggested that company marketers consciously promoted the drug for off-label indications over several years: <blockquote> Patterson was asked about a 'Seroquel Strategy Summary' issued in December 2000, which described the broadening of Seroquel use 'on and off label' as a sales goal. While doctors are free to prescribe any medicine to treat a given condition, it is illegal for drug companies to promote medicines for uses not approved by the U.S. Food and Drug Administration. 'The company has standards and procedures to ensure its sales representatives do not promote off label,' Patterson testified. Still, the goal of off-label promotion remained in strategy summaries for the years 2001 or 2002, he acknowledged. </blockquote> Coupled with previous revelations (see posts noted above), it looks like the marketers were employing an integrated strategy combining a variety of deceptions, the sort of broad based <a href="http://hcrenewal.blogspot.com/search/label/stealth%20marketing">stealth marketing </a>approach we have seen employed to promote other health care products. Such strategies undoubtedly have lead to the prescribing of expensive drugs when other treatments, or no treatment would be better, and have helped support the high prices charged for products that are not necessarily so good for the many patients who have ended up getting them. Of course, the money thus generated has let many executives of the companies that employ such marketing strategies become rich. As Bloomberg reported: <blockquote> Patterson, who reported directly to AstraZeneca’s chief executive officer, was paid more than $1 million at one point during his tenure at the company. He retired April 1 as executive director of product development, and is the highest- ranking AstraZeneca executive to testify in open court in lawsuits claiming the company withheld information about the risks of Seroquel. </blockquote> In my humble opinion, if we really want to reform health care in the US (and around the globe), we need to challenge how health care organizations have used their ability to sponsor medical research to manipulate its design, implementation, analysis and dissemination, and when necessary, to suppress its results to favor their vested interests. We also need to challenge systematically deceptive marketing practices designed to make products and services appear more useful than they really are, thus supporting exaggerated prices and prompting overuse. Unless we challenge these and some other causes of excess prices and excess use, attempts to provide universal health insurance and access will bankrupt us all. (And to preempt anyone in the audience who may recoil from anything that restricts the freedom of action of health care corporations - tell me how manipulation of research, suppression of research, and deceptive marketing is necessary for innovation or for adequate revenues to support good products? I am not arguing for hamstrung companies. I am arguing for honest business practices.) Hat tip to <a href="http://pharmagossip.blogspot.com/2009/10/astrazeneca-seroquel-weight-of-evidence.html">PharmaGossip</a>.

More on the Misleading Promotion of Seroquel

Previous posts ( here and here ) noted internal documents from AstraZeneca made public during litigation about its blockbuster atypical ant...

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BLOGSCAN - The Over-Selling of Seroquel

BLOGSCAN - The Over-Selling of Seroquel

The anonymous blogger on the Clinical Psychology and Psychiatry blog has been hard at work on the story of how research on Seroquel (quetiap...

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"Buried Data," a "Smoke-and-Mirrors Job" and a "Positive Spin" on a "Cursed Study"

Documents produced on discovery and recently unsealed during litigation suggested how <a href="http://www.astrazeneca-us.com/">AstraZeneca</a> handled clinical research data in the marketing of its atypical anti-psychotic drug <a href="http://www.seroquel.com/">Seroquel </a>(quetiapine). As <a href="http://www.bloomberg.com/apps/news?pid=20601087&sid=aS_.NqzMArG8&refer=home">reported by Bloomberg</a>, <blockquote> AstraZeneca Plc 'buried' unfavorable studies on its antipsychotic drug Seroquel, according to an internal e-mail unsealed as part of litigation over the medicine. The drugmaker failed to publicize results of at least three clinical trials of Seroquel and engaged in 'cherry picking' of data from one of those studies for use in a presentation, an AstraZeneca official said in a December 1999 e-mail unsealed yesterday under an agreement between the company and lawyers for patients. The London-based company faces about 9,000 lawsuits claiming it failed to properly warn users that Seroquel can cause diabetes and other health problems. 'The larger issue is how we face the outside world when they begin to criticize us for suppressing data,' John Tumas, an AstraZeneca publications manager, told colleagues in the e-mail. One unsealed document showed AstraZeneca officials considered Trial 15, one of the studies Tumas described as 'buried,' to be a problem because it didn’t produce favorable results on the issue of weight gain for patients taking the drug. Gaining weight can be a factor in the development of diabetes. Richard Lawrence, an AstraZeneca official, said in a February 1997 e-mail that the company had engaged in a 'great smoke-and-mirrors job' in dealing with U.S. and Canadian investigators on the trial’s results. 'Adopting the approach Don has outlined should minimize (and dare I venture to suggest) could put a positive spin (in terms of safety) on this cursed study,' Lawrence said in the e- mail. It isn’t clear from the e-mail which person Lawrence is referring to. In his December 1999 e-mail, Tumas said that AstraZeneca had 'buried trials 15, 31, 56,' and was considering a study listed as COSTAR. Details of the trials weren’t specified in the e-mail. Tumas chastised colleagues for using favorable data produced by Trial 15 without disclosing the full study results, according to his unsealed e-mail. 'There has been a precedent set regarding ‘cherry picking’ of data,' which was used in “the recent Velligan presentations,' he said. 'Thus far, I am not aware of any repercussions regarding interest in the unreported data.' The publications manager indicated that AstraZeneca had a favorable reputation for engaging in 'ethical behavior' when it came to disclosing study results on its drugs. 'We must decide if we wish to continue to enjoy this distinction,' Tumas wrote. 'The reporting of the COSTAR results will not be easy,' he added. 'We must find a way to diminish the negative findings. But, in my opinion, we cannot hide them.' </blockquote> So here we have more evidence about a big pharmaceutical company suppressing and manipulating data from the clinical research when its results proved unfavorable to its product. The unsealed evidence, when added to many other cases we have discussed, suggest that manipulation and suppression of clinical research data to support companies' vested interests is a common practice by commercial health care firms, including but not restricted to pharmaceutical, biotechnology, and device companies. As we have said before, suppression and manipulation of research amounts to post-hoc abuse of research subjects who volunteered their participation believing that it would advance science and health care. Furthermore, suppression and manipulation of research can deceive physicians into prescribing tests and treatments that will fail to help, or even harm patients, and deceive patients into thinking that they are getting the best possible tests and treatments, when, again what they are getting is ineffective or even harmful. In my humble opinion, there is an increasingly strong argument that clinical research should not be controlled, and probably should not be done at all by organizations with vested interests in the research producing results favorable to their products. See additional comments about the Seroquel litigation on the Clinical Psychology and Psychiatry blog <a href="http://clinpsyc.blogspot.com/2009/02/seroquel-becomes-zyprexa-part-2-but.html">here</a>, and the Carlat Psychiatry Blog <a href="http://carlatpsychiatry.blogspot.com/2009/02/of-seroquel-sex-and-secret-documents.html">here</a>. ADDENDUM (2 March, 2009) - See detailed comments on the apparent manipulation of a meta-analysis of Seroquel versus a "typical" anti-psychotic, haloperidol, <a href="http://clinpsyc.blogspot.com/2009/03/internal-documents-suggest-that.html">on the Clinical Psychology and Psychiatry Blog</a>.

"Buried Data," a "Smoke-and-Mirrors Job" and a "Positive Spin" on a "Cursed Study"

Documents produced on discovery and recently unsealed during litigation suggested how AstraZeneca handled clinical research data in the mar...

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