healthy4u: GlaxoSmithKline

GlaxoSmithKline's Marketing Firm Promised "Clinical Trials Could be Your Solution" to Poor Graduate Students

We have frequently raised concerns about the increasing domination of clinical research, particularly clinical trials, by those with vested in interests in the research producing particular results.  In particular, drug, biotechnology and device companies often sponsor trials meant to evaluate their own products.  Often it appears that commercial trial sponsors <a href="http://hcrenewal.blogspot.com/search/label/manipulating%20clinical%20research">manipulate</a> various aspects of research design, implementation, analysis, and dissemination to increase the likelihood of a result favorable to their interests.  Furthermore, when even such manipulation fails to produce the desired result, particular studies may simply be <a href="http://hcrenewal.blogspot.com/search/label/suppression%20of%20medical%20research">suppressed</a>, that is, hidden. Clinical Trial Participation as "Your Solution" to Graduate Students' Money Woes A recent story, first told on the In-Pharma Technologist web site, gave an example of how trial recruitment could be gamed so as to produce more compliant study subjects. Since that web-site does not allow copy and pasting of even a few sentences of its content, I will quote, instead, from a subsequent <a href="http://www.theguardian.com/money/2014/jun/22/glaxosmithkline-gsk-interns-drug-trial-pitch">article in the Guardian</a>. <blockquote class="tr_bq">GlaxoSmithKline  the pharmaceuticals multinational, has apologised after being accused of playing on the hardship of unpaid interns to recruit them to take part in clinical trials. A marketing firm working for the FTSE 100 company sought to place a blog on careers advice websites boasting that involvement in drug trials could help graduates to finance their way through unpaid work placements. In a proposed 'guest blog' for the website <a href="http://graduatefog.co.uk/2014/3433/unpaid-interns-targeted-for-clinical-trials/" title="">Graduate Fog</a>, an employee at TouchPoint Digital, working on behalf of GSK, wrote: 'Clinical trials could be your solution.'</blockquote> The "guest blog" proposed that many graduate students "would prefer an immediate income to tide you over for the coming months."  So, <blockquote class="tr_bq">Clinical trials could be your solution. Depending on the length of the study, you could earn up to £2,000 per trial for up to 4 trials a year, plus reasonable travel expenses.</blockquote> This was not a one-off, <blockquote class="tr_bq"> Touchpoint provided examples of similar articles previously published on websites targeted at students. In an <a href="http://graduatefog.co.uk/2014/3433/unpaid-interns-targeted-for-clinical-trials/" title="">email to the founder of Graduate Fog, Tanya de Grunwald</a>, it added: 'Your readers would also benefit if there is a small link at the end of the article to the GSK website, which is the biggest pharmaceutical company in the UK, so that if they want to find out more or get answers to more specific questions they can do so.'</blockquote> Excessive Inducement The story was <a href="http://blogs.wsj.com/pharmalot/2014/06/23/glaxo-dumps-firm-for-praying-on-college-grads-for-clinical-trials/">picked up by Ed Silverman at the PharmaLot blog</a> in the US, who pointed out how TouchPoint Digital appeared to be supplying an excessive inducement to vulnerable subjects, <blockquote class="tr_bq">Tanya de Grunwald, who runs the Graduate Fog website in the U.K., objected to the tone of the overture. 'Some of my readers are feeling very low, vulnerable and desperate for money,' she wrote us in an e-mail after openly questioning the recruiting tactic in <a data-ls-seen="1" href="http://graduatefog.co.uk/2014/3433/unpaid-interns-targeted-for-clinical-trials/">a note to readers</a> on her website last week. 'Many are unemployed. Others are in low-paid graduate jobs or doing unpaid internships.' 'Suggesting that participating clinical trials is a great way to earn easy cash is not just crass – I think it’s irresponsible. Surely, the more desperate someone is for money, the more likely they are to be dazzled by the financial benefits and less careful about weighing up the risks.'</blockquote> A long time ago, that is, from 2006 - 2008, we published a series of posts about how <a href="http://hcrenewal.blogspot.com/search/label/contract%20research%20organizations">contract research organizations</a> running clinical research projects for commercial health care firms often preyed on financially and otherwise vulnerable research subjects by offering what would appear to such people to be dazzling remuneration.  For example, we discussed the trials by SFBC International (later PharmaNet Development Group, and now apparently <a href="http://www.inventivhealthclinical.com/">Inventiv Health Clinical</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). In 2008, 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.  Excessively zealous recruiting designed to tempt vulnerable subjects with money appears unethical, and may be dangerous for these subjects. How Excessive Inducement Could Lead to Invalid Trial Results Not only is such a practice apparently unethical and dangerous, it could endanger patients outside the research projects in question by producing invalid research.  Subjects who could be dazzled by such inducements might avoid disclosing conditions which would otherwise exclude them from particular research projects, or participate in multiple projects without sufficient or any wash out periods in between, meaning that one treatment's effects could confound another.  (Note that the blog post proposed by the marketer above suggested that subjects could participate in multiple trials during one year.)  Furthermore, subjects desperate to complete studies and earn their fees might avoid reporting adverse effects to avoid the risk of premature termination of their participation, or avoid protesting questionable actions by the researchers.    But now in the modern era of the Internet and social media, overzealous recruitment using monetary lures is still going on.  As per PharmaLot, <blockquote class="tr_bq">One expert believes the flap is not surprising, because drug makers are under pressure to maintain a steady stream of clinical trial recruits. 'Middle class folks just sit back and wait until the drug reaches the market. Poor folks are the guinea pigs in an economy that is more and more uneven, and uncertain by the day,' says Roberto Abadie, a senior researcher at the Social Networks Research Group at John Jay College, City University of New York, and author of ‘The Professional Guinea Pig: Big Pharma and the Risky World of Human Subjects.' </blockquote> A Belated Response from GSK Apparently only after the story broke did GSK notice there was a problem.  Again, per PharmaLot, A Glaxo spokeswoman blamed the outside marketing firm for the episode. In an e-mail, she wrote us that 'we would agree that the tone used in the ads… is wrong. It trivializes the role of clinical trials in developing new medicines and the part that volunteers play in that process. This isn’t acceptable and we’re looking into what happened.' Whether GSK was properly supervising the marketing firm, and whether GSK had provided incentives that might have lead to overzealous recruitment were not addressed. Summary This story is yet another reminder that health care professionals, health policy makers, and the public at large should be extremely skeptical of clinical research sponsored (and controlled) by those with vested interests in the research results turning out a certain way, particularly clinical trials run by drug, biotechnology, or biotechnology companies meant to assess those companies' own products. However, note that very rarely do published clinical trial reports provide enough detail about subject recruitment to determine whether overzealous recruitment and undue inducements may have lead to enrollment of subjects who should have been excluded, under reporting of adverse effects, etc. In my humble opinion, we need to reassess current policies that allows organizations with such obvious conflicts of interest to run experiments on human beings (which is what clinical trials are.) By the way, this story is also a reminder that most big drug, device and biotechnology firms seem to be associated again and again with dodgy clinical research.   For example, see what we have previously written about GSK<a href="http://hcrenewal.blogspot.com/search/label/GlaxoSmithKline"> here</a>.

GlaxoSmithKline's Marketing Firm Promised "Clinical Trials Could be Your Solution" to Poor Graduate Students

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24 Jun 2014

Long After the Start of the "War on Terror," a Conflict of Interest about an Anthrax Scare Comes to Light

In May, David Willman writing for the Los Angeles Times broke a <a href="http://www.latimes.com/news/nationworld/nation/la-na-anthrax-resistant-20130519-dto,0,3192936.htmlstory">story</a> of a somewhat new variant on the conflict of interest theme, one that has not gotten a lot of attention, but should. The issue was medical, with a twist, - how to best treat a bioterror attack with anthrax engineered to be resistant to multiple drugs, an event that luckily is not known to ever have occurred.  The story came from the bad old days of the "war on terror," but only has now come to light years later. The Alarm Raiser The story opened thus, <blockquote class="tr_bq">Over the last decade, former Navy Secretary Richard J. Danzig, a prominent lawyer, presidential advisor and biowarfare consultant to the Pentagon and the Department of Homeland Security, has urged the government to counter what he called a major threat to national security. Terrorists, he warned, could easily engineer a devastating killer germ: a form of anthrax resistant to common antibiotics.</blockquote> In particular, <blockquote class="tr_bq">Danzig began warning about antibiotic-resistant anthrax after the terrorist attacks of Sept. 11, 2001, and the mailings of anthrax-laced letters that fall. The powdered anthrax in the letters killed five people but was not resistant to common antibiotics. Asked what gave rise to his concern about resistant strains, Danzig cited conversations with 'people whose technical skills exceed mine.' One of them, Dr. Robert P. Kadlec, a bioterrorism advisor in the Bush White House, said he and others were concerned that terrorists could develop such a weapon. Danzig has sounded the alarm in published papers and in private briefings and seminars for biodefense and intelligence officials. In a 2003 report funded by the Pentagon, "<a href="http://documents.latimes.com/catastrophic-bioterrorism-what-be-done/" target="_blank">Catastrophic Bioterrorism — What Is To Be Done?</a>" he wrote that it would be 'quite easy' for terrorists to produce antibiotic-resistant anthrax. He has expanded on that theme over the years, including in a 2009 paper for the Pentagon. In the 2003 report, published while raxi [raxibacumab, an anthrax anti-toxin] was in development at Human Genome, Danzig said a drug to combat resistant strains of anthrax should be produced 'as soon as possible' and that stockpiling such a treatment, 'even if expensive and in limited supply' would deter an attack. John Vitko Jr., a top Homeland Security official during the Bush and Obama administrations, said he turned frequently to Danzig for advice on biodefense matters — and read and 'paid attention to' his 'Catastrophic Bioterrorism' report.</blockquote> Note that while Danzig is a lawyer, and certainly not a physician or biomedical researcher, he had major credibility in the defense field, particularly in anti-terrorism, so his recommendations had great influence. <blockquote class="tr_bq">He served as a Pentagon appointee during the Carter administration and as undersecretary and then secretary of the Navy under President Clinton. He has a long-standing interest in biowarfare. During the 2008 presidential campaign, Danzig advised then-Sen. Barack Obama on national security and bioterrorism. After Obama's election, Danzig was named to the Pentagon's Defense Policy Board and the President's Intelligence Advisory Board, in addition to his consulting positions with the Defense Department and Homeland Security.</blockquote> So apparently at least partly due to Mr Danzig's persistent warnings, the government took action, <blockquote class="tr_bq"> In 2004, President Bush signed into law Project BioShield, which provided billions of dollars for biodefense drugs. The contracts are administered by the Department of Health and Human Services, based on advice from federal agencies and consultants. Homeland Security must certify the need for a drug before the government can buy it.  Danzig, through his seminars, writings and consulting duties, has helped frame the discussion over whether a given biological threat is 'material' and whether the government should stockpile medicines to defend against it.</blockquote> Also, <blockquote class="tr_bq">Speaking of Danzig's broader role as a government advisor, Vitko said: 'Richard's got incredible insights into this and I think has made major contributions' He called Danzig one of 'the major bio player' and said his views had informed a range of policy considerations, including 'how many countermeasures do you need, of what kind.' It was in response to advice from Vitko and his staff that Homeland Security Secretary Tom Ridge in 2004 declared anthrax a 'material threat,' the certification required for the government to buy drugs to fight it. The drug the government bought was raxibacumab, or raxi, an anthrax anti-toxin made by Human Genome Sciences Inc.   In 2006, the Department of Health and Human Services finalized its first order of raxi — 20,000 doses at a cost of $174 million. That year, Ridge's successor, Michael Chertoff, signed a second, more specific declaration, adding 'multi-drug-resistant' anthrax to the government's list of material threats. Asked the basis for the second declaration, Vitko said: 'I think the concern was more forward-looking, and saying, 'How could the threat evolve, and are we prepared for that?'' Since 2009, the Obama administration has ordered an additional 45,000 doses of raxi for $160 million.</blockquote> There was just one catch. The Undisclosed Conflict Mr Danzig had a largely undisclosed conflict of interest.  He was on the board of directors of Human Genome Sciences Inc, the company whose drug his constant warnings and exhortations lead the government to buy. <blockquote class="tr_bq">When Human Genome named Danzig to its board on May 24, 2001, the company's chief executive said his high-level federal experience would 'serve us well.'</blockquote> He thus was on the board on September 11, 2001, and later when the events on that day and soon after apparently induced him to start sounding the alarm about resistant anthrax, and he stayed on the board as he continued sounding alarms, and after the government started buying his company's drug. <blockquote class="tr_bq">During his 11-year tenure on the board, which ended in August, Danzig collected at least $1,054,255 in director's fees and by cashing in grants of Human Genome stock and stock options, according to Fred Whittlesey of Compensation Venture Group, who reviewed the company's Securities and Exchange Commission filings for The Times. Nearly half of Danzig's compensation came from the stock options, of which he had been granted 184,000 by the end of 2011, Whittlesey said.</blockquote> Danzig did not seem to think that serving on the board of the company which made the primary drug directed at the perhaps hypothetical disease about which Danzig was sounding the warning constituted any sort of conflict of interest. <blockquote class="tr_bq">Danzig said in an interview that he believed his position at Human Genome posed no conflict. He said he had tried to improve policymakers' understanding of biodefense issues, including the threat of antibiotic-resistant anthrax, but never lobbied the government to purchase raxi. 'My view was I'm not going to get involved in selling that,' Danzig said. 'But at the same time now, should I not say what I think is right in the government circles with regard to this? And my answer was, 'If I have occasion to comment on this, it ought to be in general, as a policy matter, not as a particular procurement.' 'I feel that I've acted very properly with regard to this'' he said.</blockquote> He also apparently did not feel he needed to disclose his board membership to most of the people he was trying to persuade to be alarmed about resistant anthrax, and to pursue a treatment, such as that made by the company on whose board he sat. <blockquote class="tr_bq"> A number of senior federal officials whom Danzig advised on the threat of bioterrorism and what to do about it said they were unaware of his role at Human Genome. Dr. Philip K. Russell, a biodefense official in the George W. Bush administration who attended invitation-only seminars on bioterrorism led by Danzig, said he did not know about Danzig's tie to the biotech company until The Times asked him about it.</blockquote> Also, <blockquote class="tr_bq"> Vitko said he knew nothing of Danzig's involvement with Human Genome until a Times reporter asked him about it. 'I'm surprised I didn't,' Vitko said. 'I'm not aware of it.' Five other present or former biodefense officials who conferred with Danzig said they, too, had been unaware of his position with the company. Danzig, they said, made no mention of it in their presence during group discussions he led or in smaller meetings.</blockquote> Furthermore, <blockquote class="tr_bq">A Times search found seven papers Danzig had written on bioterrorism since 2001. In only one of those did he disclose his tie to Human Genome. As an advisor to the federal government, Danzig is required to file confidential forms annually, revealing any outside affiliations but not his related compensation. Danzig said he had noted his position with the biotech firm on the forms. Asked whether he mentioned his corporate role during contacts with government officials, Danzig replied: 'If I thought any of it posed a potential conflict that might cause somebody who knew about it to discount my views, I would tell them.'</blockquote> Some people disagreed with Danzig's failure to perceive a conflict of interest <blockquote class="tr_bq"> 'Holy smoke—that was a horrible conflict of interest,' said Russell, a physician and retired Army major general who helped lead the government's efforts to prepare for biological attacks.</blockquote> The Take-Over by a Familiar Corporation By the way, Human Genome Science was eventually bought out by a bigger company which has had its own sets of issues regarding conflicts of interest, GlaxoSmithKline, <blockquote class="tr_bq"> Human Genome was acquired by GlaxoSmithKline in August [presumably 2012] for $3.6 billion.</blockquote> It may yet stand to make even more money from raxi, <blockquote class="tr_bq"> Because raxi loses its potency after three years in storage, the government's supply will expire as of 2015, according to federal documents and people familiar with the matter. </blockquote> Summary This appears to be a variant on the "key opinion leader" (KOL) theme writ large.  Mr Danzig clearly functioned as a very major key opinion leader about bioterrorism.  Like many KOLs we have previously discussed, he had financial interests that favored the company whose drugs his key opinion leadership seemed to be favoring.  His influence seems to have lead to huge purchases of these drugs. Like many KOLs who are physicians or health care academics, Mr Danzig seems utterly blind to the possibility that his multiple efforts to emphasize the importance of the supposed disease for which his company made a drug could somehow be viewed as a conflict of interest, or to why failure to tell his audiences about his major relationship to this company might have appeared just a small bit dishonest.  We have seen many medical/ health care KOLs who deny that somehow their opinions could have been influenced by their financial relationships, or that their audiences deserved at least to be aware of these relationships.  Yet, of course, Mr Danzig is not a doctor, and he was trying to influence government purchasers of drugs, not physician prescribers of it. It does seem that the leadership of health care organizations, particularly but certainly not limited to pharmaceutical and biotechnology companies, have no lack of imagination about how to construct financial relationships with influential people who could help sell their products, whether or not they acknowledge what amounts to their marketing roles. Given that this story involved influencing the government, it will be interesting to see at this late date whether it results in any legal action.  After all, as David Willman pointed out, <blockquote class="tr_bq"> Federal law bars U.S. officials, including consultants, from giving advice on matters in which they or a company on whose board they serve have 'a financial interest.'</blockquote>It will also be interesting to see if it gets any more attention.  Only a few blogs have noted it, but at least they included <a href="http://www.the-scientist.com/?articles.view/articleNo/35639/title/Selling-an-Anthrax-Scare-/">The Scientist</a>. Yet our country has an unfortunately very long history of corporate leaders getting close to political leaders who then may overlook the legal niceties when their friends' interests are at stake.  Nonetheless, true health care reform would require all those who have decision making power over patients, health policy, or the public health to be completely transparent about their conflicts of interest, and would ban the more serious variants of conflicts of interest, even if that might cost some already rich people a bit of money.  I am not holding my breath, however, about when this might happen.

Long After the Start of the "War on Terror," a Conflict of Interest about an Anthrax Scare Comes to Light

In May, David Willman writing for the Los Angeles Times broke a story of a somewhat new variant on the conflict of interest theme, one that has not gotten a lot of attention, but should.The issue was …

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05 Jun 2013

WALK THE WALK

<div class="MsoNormal"><o:p>WALK THE WALK</o:p></div><div class="MsoNormal"> </div><div class="MsoNormal">For some time a jeremiad theme has been dominant in the psychiatric sector of the <a href="http://hcrenewal.blogspot.com/2009/01/academic-industrial-complex.html">academic-industrial complex</a>. Blockbuster psychiatric medications are going off patent, the pipeline is viewed as alarmingly empty, and several corporations are scaling back or even abandoning their research programs in this area. Analyses of the reasons range from the <a href="http://www.ncbi.nlm.nih.gov/pubmed/17080187">enlightened</a> to the <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=22837348">pragmatic</a> to the <a href="http://www.psychiatrictimes.com/all/editorial/psychiatrictimes/pdfs/KrystalPresidentsLetter2012.pdf">pedantic</a> to the <a href="http://www.thecarlatcmeinstitute.com/blog/2011/08/has-stephen-stahl-gone-off-the-deep-end-you-decide/">foolish</a>. Everyone predicts that things will turn bleak in academic clinical research if the corporate spigot is turned off.</div><div class="MsoNormal"> </div><div class="MsoNormal">Lost in the wailing is a clear understanding that the defecting corporations are acting out of their own enlightened self interest. For 50 years, no fundamentally incisive innovations have occurred, so the defectors are telling the academics to get their act together in respect of better understanding disease mechanisms. Trouble is, too many academic clinical investigators have devolved into key opinion leaders promoting corporate marketing messages at the expense of generating original clinical science. Now they are squawking about being caught with their pants down.</div><div class="MsoNormal"> </div><div class="MsoNormal">The latest academic psychiatrist to opine about this issue is Steven Hyman at Harvard Medical School. In a new commentary that has just <a href="http://www.dana.org/news/cerebrum/detail.aspx?id=41290">appeared</a>, Dr. Hyman talks up his favorite theme of translational medicine, which sounds lovely until you perceive that he has no contemporary examples of same in psychopharmacology. It’s all airy rhetoric. Dr. Hyman is not just a Harvard professor – he is a former Director of the National Institute of Mental Health (NIMH). Then he was Provost at Harvard under President Larry Summers. Now he is Director of a psychiatric research center at Harvard. </div><div class="MsoNormal"> </div><div class="MsoNormal">Someone else who noticed Dr. Hyman’s new <a href="http://www.dana.org/news/cerebrum/detail.aspx?id=41290">commentary</a> is our fellow blogger Dr. John M. (Mickey) Nardo across at <a href="http://1boringoldman.com/">1Boringoldman.com</a>. His take on the Hyman piece is right on target. Basically, the Hyman commentary is a hortatory fantasy that we can all do better by buying in to his vision of interdisciplinary research, pooling the efforts of academia, industry, and government. Problem is, his vision hasn't worked so far. Here is an example.</div><div class="MsoNormal">   </div><div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in;">Towards the end of his term as NIMH Director, Dr. Hyman set the ball rolling for new centers cast in his mold of translational research. Dr. Nardo <a href="http://1boringoldman.com/index.php/2013/04/05/whither-the-crisis/">mentioned</a> “… a bunch of centers that haven’t produced very much.” The model of such failed centers is the one that existed at Emory University under the direction of Charles Nemeroff. It was called the Emory-GlaxoSmithKline-NIMH Collaborative Mood Disorders Initiative 5U19MH069056 (Principal Investigator Charles Nemeroff). It was conceived with all the right buzzwords about innovative models of drug discovery and translational benefit for patients through partnerships of academic centers with commercial drug makers (the Request for Applications (RFA) actually used this language). From the start, the Initiative was poorly managed and it never lived up to its billing. </div><div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in;"> </div><div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in;">Annual Progress Reports from the Initiative to NIMH, obtained through a FOIA request, reveal unacceptably low scientific productivity, and lack of leadership to promote the intended scientific synergies among laboratories. When I assessed the overall productivity of this project four years after the end of the first 5-year funding period, it was apparent that the U.S. taxpayer received little value for the $5.3 million investment by NIMH. Only 7 original scientific publications could be attributed to the federal support (that count excludes a host of potboiler review articles and other academic padding). Five of these 7 originated from a single participating laboratory at Emory. The NIMH component, under Dennis Charney, also was a serious underperformer.</div><div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in;"> </div><div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in;">The collaborating drug company GlaxoSmithKline obtained valuable preclinical information from the Emory laboratories, much of which has never been published even though federal funding supported the work. If the data are being treated as confidential proprietary information by GSK, then that posture would be contrary to the spirit of the original RFA. Maybe GSK just decided it was worthless data. In addition, GSK benefited from the conduct of a Phase II clinical trial of one of their candidate drugs in posttraumatic stress disorder (PTSD), even though this study returned a negative result. Even worse, the trial did not meet the stated criteria of the RFA. It was not based on any well founded theory of PTSD. Instead, it was a routine, exploratory study of a new compound. Because the study design did not permit strong inference, nothing substantive was learned from the negative result. This Phase II trial could have been performed better and less expensively by GSK itself as a normal business activity. GSK certainly did not need scarce NIMH dollars for this routine, early Phase II trial. The Emory-GSK-NIMH Initiative added no scientific value.</div><div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in;"> </div><div class="MsoNormal">Notwithstanding the clear evidence of under-productivity, NIMH under Director Thomas Insel, MD, continued the Initiative for all 5 years of the original funding period, and then renewed the Initiative for a second 5 year period at an increased funding level under a new P.I., Helen Mayberg, M.D. Dr. Mayberg is a respected clinical scientist, but she is not a psychiatrist, she is not a psychopharmacologist, and she has no track record of research in the priorities announced by the RFA. What actually is going on? Did NIMH just hand a favor to Dr. Insel’s former employer, Emory University, to the tune of another $6 million?</div><div class="MsoNormal"> </div><div class="MsoNormal">One lesson of this episode is that the chatter by federal scientific administrators (Hyman, Insel) about translational research strategies and innovative models of drug discovery is mostly vacuous rhetoric. The RFA was an imprudent conceit to begin with, having no base in solid clinical science, and this expensive Initiative failed catastrophically to meet its grandiose objectives. It is ironic that Dr. Hyman presumes to scold and sermonize to the field yet again about translational research, as it was he who set the ball rolling in the first place for the disastrous Emory-GlaxoSmithKline-NIMH Collaborative Mood Disorders Initiative. Last time I looked, nobody has been held accountable for the failure of the Initiative. Where is NIMH Director Thomas Insel when we need him to set standards of accountability and ethics?</div><div class="MsoNormal"> </div><div class="MsoNormal">So, the next time you hear academic psychiatrists lamenting how bad it is, remind them about this scandalous example of waste and mismanagement of federal research funding. Cleaning up cesspools like this would be a step to unblocking the drug development pipeline. And we need leaders who walk the walk, not just talk the talk.</div><div class="MsoNormal"> </div>

WALK THE WALK

WALK THE WALKFor some time a jeremiad theme has been dominant in the psychiatric sector of the academic-industrial complex. Blockbuster psychiatric medications are going off patent, the pipeline is vi…

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06 Apr 2013

The Tragic Case of Aaron Swartz: Unequal Justice for Web Activists vs Health Care Corporate Executives

The recent tragic case of the suicide of Aaron Swartz raises many issues, and has inspired an outpouring of news coverage and internet discussion.  Yet one issue it should raise that has not received much notice so far is that of how individuals and top executives are treated differently before the law. Summary of the Case Aaron Swartz was a prodigy who <strike>developed</strike>  helped develop the RSS system for disseminating updates on web-site contents, and who helped develop the Reddit web-site.  He was an advocate for information freedom, and more broadly, <a href="http://www.nakedcapitalism.com/2013/01/aaron-swartzs-politics.html">according to</a> Matt Stoller, "a political activist interested in health care, financial corruption, and the drug war."  Furthermore, he "recognized that politics is a corrupt money driven system, but also that it could be cracked if you spent the time to understand the moving parts." Although apparently very well known among internet activists and computer scientists, Mr Swartz did not attract a lot of mainstream media attention, at least until 2011 when he was arrested "on a series of felony counts including wire fraud, computer fraud, unlawfully obtaining information from a protected computer and recklessly damaging a protected computer," <a href="http://www.nytimes.com/2011/07/25/business/media/aaron-swartzs-web-activism-may-cost-him-dearly.html">according to the New York Times</a>.  His alleged crime was that he downloaded thousands of scientific scholarly articles from the site JSTOR, and was accused of intending to make them publicly available for free.  Note that the articles were already publicly available, but only online through expensive subscriptions.  At the time, the US Department of Justice took this to be a very serious crime: <blockquote class="tr_bq">'Stealing is stealing, whether you use a computer command or a crowbar, and whether you take documents, data or dollars,' the United States attorney for Massachusetts, Carmen M. Ortiz, said last week in a statement about the case. 'It is equally harmful to the victim whether you sell what you have stolen or give it away.' </blockquote> The charges Ms Ortiz filed lead to Mr Swartz's arrest <blockquote class="tr_bq">on a series of felony counts including wire fraud, computer fraud, unlawfully obtaining information from a protected computer and recklessly damaging a protected computer. If convicted on all counts, the Justice Department said he could face up to 35 years in prison and $1 million in fines. </blockquote> Yet Mr Swartz certainly was not accused of either violence or of planning to personally profit from his alleged crimes.  At the time of his arrest, the severity of the allegations baffled many: <blockquote class="tr_bq"> 'This makes no sense,' said David Segal, executive director of Demand Progress, an organization Mr. Swartz founded to rally support online for an open Internet. 'It’s like trying to put someone in jail for allegedly checking too many books out of the library.'</blockquote> JSTOR got the hard drives that contained the articles in question back from Mr Swartz, and planned no further action: <blockquote class="tr_bq">Asked if it was pleased that someone misusing the service could be brought to justice, a spokeswoman for Jstor wrote in an e-mail response: 'We wanted the content back, and we were able to secure it and ensure it wasn’t distributed. We were not interested in further legal action around this incident. We have no comment on the prosecution or how they have chosen to characterize it.'</blockquote> Since 2011 the case got little notice until Mr Swartz ended his own life this month.  After his death, his family and partner issued a statement, as <a href="http://www.guardian.co.uk/technology/2013/jan/13/aaron-swartz-family-mit-government">reported by the Guardian</a>: <blockquote class="tr_bq">In a statement released late Saturday, Swartz's parents, Robert and Susan, siblings Noah and Ben and partner Taren Stinebrickner-Kauffman said the Reddit<a href="http://www.guardian.co.uk/technology/reddit" title="More from guardian.co.uk on Reddit">t</a> builder's demise was not just a 'personal tragedy' but 'the product of a criminal justice system rife with intimidation and prosecutorial overreach'. They also attacked the Massachusetts Institute of Technology (MIT) for not supporting the internet activist in his legal battles and refusing to stand up for 'its own community's most cherished principles'.</blockquote> And according to the New York Times <a href="http://www.cnbc.com/id/100376112">(via CNBC</a>), Harvard Professor Larry Lessig, Director of the Safra Center for Ethics, where Swartz had been a fellow protested <blockquote class="tr_bq">the idea that he could have seen serious prison time was infuriating. Lawrence Lessig, the Harvard Law professor who founded Creative Commons to advocate greater sharing of creative material online, called the prosecution's case absurd and said that boxing in Mr. Swartz with an aggressive case and little ability to mount a defense ''made it make sense to this brilliant but troubled boy to end it.'</blockquote>  Hounding Swartz but Failing to Pursue Health Care Corporate Executives The Daily Beast just ran <a href="http://www.thedailybeast.com/articles/2013/01/15/aaron-swartz-s-unbending-prosecutors-insisted-on-prison-time.html">a story</a> that suggests that Swartz should have known better to have done something that would have attracted the wrath of one of the toughest federal prosecutors, but one who is also a "liberal's dream."  It opened its piece on US Attorney Carmen Ortiz thus: <blockquote class="tr_bq"> Until she was accused of driving the 26-year-old cyber wunderkind and public-access activist Aaron Swartz<a href="http://www.thedailybeast.com/articles/2013/01/13/mourning-aaron-swartz-internet-activist-and-free-information-advocate.html"></a> to suicide<a href="http://www.thedailybeast.com/articles/2013/01/14/aaron-swartz-s-thought-crime-was-tragically-treated-like-real-crime.html"></a>, the top federal prosecutor in Massachusetts was a liberal’s dream.  Not for nothing was United States Attorney Carmen Ortiz championed by the late Sen. Edward Kennedy and appointed by President Obama nearly four years ago.</blockquote> Then, it suggested how tough Ms Ortiz really is: <blockquote class="tr_bq">She is Hispanic and was raised in a New York housing project, and after her husband died of cancer she raised two daughters on her own. She has taken on political corruption, and she has been so aggressive against white-collar crime that her office collected more in forfeitures and fines than any other jurisdiction in the country. <div class="text parbase section"></div><a href="http://www.blogger.com/blogger.g?blogID=9551150" name="body_text3" style="visibility: hidden;"></a>Her avowed motive in becoming a prosecutor was because 'there’s a greater chance for justice.'</blockquote> that is a pretty amazing summary.  However, it seems decidedly at odds with Ms Ortiz's record dealing with misdeeds by health care corporations, as discussed on<a href="http://hcrenewal.blogspot.com/"> Health Care Renewal</a>.  Ms Ortiz, whose harsh views of Swartz appear above, has been quoted at least three times about three different cases on this blog.  In all instances, her quotes were in the context of legal settlements she made with large health care corporations. Forest Pharmaceuticals In September, 2010, how Ms Ortiz led the pursuit of a settlement with Forest Pharmaceuticals became apparent (look <a href="http://hcrenewal.blogspot.com/2010/09/forest-pharmaceuticals-pleads-guilty-to.html">here</a>).   The company was accused of promoting its anti-depressant Celexa for use in adolescents and children.  Such drugs have since been shown to increase the risk of suicide by such young patients, and this drug was only approved for adults.  At the time, Ms Ortiz said, "Forest Pharmaceuticals deliberately chose to pursue corporate profits over its obligations to the F.D.A. and the American public."  Although the offense may have lead to use of the drug by many adolescents and children, and hence may have lead to some of them attempting or committing suicide, the case was settled only with fines.  As is usual in such legal settlements, no individual corporate executive who authorized or lead the off-label and potentially dangerous marketing of the drug was arrested, or accused, and none suffered any negative consequences. GlaxoSmithKline In October, 2010, how Ms Ortiz led the pursuit of a settlement with GlaxoSmithKline became apparent (look <a href="http://hcrenewal.blogspot.com/2010/10/glaxosmithkline-subsidiary-pleads.html">here</a>.)  The company was accused of selling drugs that were not what they appeared to be, apparently because the wrong drugs were put in labelled containers.  Obviously, taking one drug, like Paxil, GSK's anti-depressant which has a number of known adverse effects, including suicide risk for adolescents and children as noted above, when a patient is supposed to be taking a wholly different drug could lead to patient harm.  At that time, Ms Ortiz said, "We will not tolerate corporate attempts to profit at the expense of the ill and needy in our society -- or those who cut corners that result in potentially dangerous consequences to consumers."   Again, while the settlement involved a guilty plea by a GSK subsidiary, again no individual corporate executive who had authority over the drug manufacturing was arrested or accused, much less suffered any negative consequences. St Jude Medical In January, 2011, Ms Ortiz led the pursuit of a settlement with St Jude Medical (look <a href="http://hcrenewal.blogspot.com/2011/01/st-jude-medical-settles-again.html">here</a>).  The company was accused of paying kickbacks to doctors to implant its cardiac defibrillators (ICDs) and pacemakers.  Obviously, providing kickbacks to doctors may have lead them to plant devices in patients who did not really need them, yet the devices and the implantation procedures can have adverse effects.  At that time, Ms Ortiz said, "The United States alleges that St Jude solicited physicians for the studies in order to retain their business and/or convert their business from a competitor's product."  Again, as is usual, the settlement did not require any executive who authorized or directed the activities leading to the kickbacks suffered any negative consequences. So in summary, in three major cases involving unethical practices by big health care corporations that could have put patients at risk, US Attorney Carmen Ortiz provided strong words, but did not apparently seek any punishment of any form of any of the corporate leaders who authorized or directed the bad, and potentially dangerous behavior.  Yet in the sorry case of Aaron Swartz, Ms Ortiz charged a gifted computer activist whose alleged crimes certainly did not put any individuals at risk of adverse medical effects or any bad physical outcomes with crimes that if proven would have lead to years in jail and millions in fines for him as an individual. Equal Justice Under the Law? So it seems ironic, or worse, that the main narrative of the Swartz case has become: well meaning but reckless hacker versus implacably tough law enforcer.  As noted above, Ms Ortiz's office appeared anything but tough when dealing with misdeeds by big pharmaceutical and device companies.  So the real question is why she went after Mr Swartz so relentlessly, when his alleged crime was non-violent and physically hurt nobody, when she failed to pursue corporate executives who enriched themselves while leading companies whose unethical practices likely harmed a lot of patients. In that light, the dark imaginings of Matt Stoller do not seem so far-fetched.  On Naked Capitalism he <a href="http://www.nakedcapitalism.com/2013/01/aaron-swartzs-politics.html">wrote</a>, <blockquote class="tr_bq"> As we think about what happened to Aaron, we need to recognize that it was not just prosecutorial overreach that killed him. That’s too easy, because that implies it’s one bad apple. We know that’s not true. What killed him was corruption. Corruption isn’t just people profiting from betraying the public interest. It’s also people being punished for upholding the public interest. In our institutions of power, when you do the right thing and challenge abusive power, you end up destroying a job prospect, an economic opportunity, a political or social connection, or an opportunity for media. Or if you are truly dangerous and brilliantly subversive, as Aaron was, you are bankrupted and destroyed.</blockquote> I did not know Aaron Swartz, but am very sorry that we have lost someone so intelligent and imaginative.  I hope one question that his untimely death raises is what has become of the idea of equal justice under the law, and how its apparent demise has enabled the dysfunction of our health care system, and our whole society.

The Tragic Case of Aaron Swartz: Unequal Justice for Web Activists vs Health Care Corporate Executives

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15 Jan 2013

'Tis the Season for Legal Settlements: GlaxoSmithKline, Eli Lilly, Orthofix, Sanofi all Settle

Reports of legal settlements by big health care organizations tend to dribble out towards the end of the year, maybe in a rush to finalize the year's accounting, maybe because the news will not register as well at times when people are distracted by holidays.  Here is a round-up in alphabetical order of some recent settlements of interest made by drug and device companies. GlaxoSmithKline Earlier this year GSK made the largest settlement, in monetary terms, ever by a pharmaceutical company (see <a href="http://hcrenewal.blogspot.com/2012/07/giant-gsk-settlement-provides-reminder.html">this post</a>).  At the end of the year it made two more.  Neither got much media attention.  The first was related to the earlier $3 billion settlement.  As <a href="http://lebanon-express.com/news/glaxosmithkline-pays-to-settle-avandia-lawsuit/article_59b5a4fe-3426-11e2-ae3b-001a4bcf887a.html">reported</a> by the [Great] Lebanon [Oregon] Express: <blockquote class="tr_bq">Oregon Attorney General Ellen Rosenblum announced in a press release that pharmaceutical giant GlaxoSmithKline has agreed to pay $90 million to Oregon and 37 other states to settle claims that it unlawfully promoted its diabetes drug, Avandia. As the co-leader of the lawsuit, Oregon will receive $3.9 million of the settlement, according to the release. The 38 attorneys general claimed in lawsuits filed Nov. 15 that GlaxoSmithKline misrepresented the cardiovascular risks posed by Avandia. A negotiated consent judgment was filed shortly thereafter.  Avandia was a blockbuster drug for GlaxoSmithKline. First approved by the Food and Drug Administration in 1999, annual sales peaked at more than $2.5 billion in 2006.</blockquote> Furthermore, <blockquote class="tr_bq"> Oregon and the 37 other states claim GlaxoSmithKline made safety claims about Avandia not supported by the scientific evidence. The states allege the company failed to disclose negative information about Avendia’s cardiovascular health effects.</blockquote> In addition to the monetary settlement, the agreement included all sorts of pledges by GSK: <blockquote class="tr_bq">As part of the consent judgment between the parties, GlaxoSmithKline agreed to reform how it markets and promotes diabetes drugs. It agreed to several conditions:  • To refrain from making false, misleading, or deceptive claims about any diabetes drug; • To refrain from making comparative safety claims not supported by substantial evidence or substantial clinical experience; • To refrain from presenting favorable information previously thought of as valid but rendered invalid by contrary and more credible recent information; •   To refrain from misusing statistics or otherwise misrepresenting the nature, applicability, or significance of clinical trials. The Consent Judgment also has the following terms that are effective for at least eight years: • GlaxoSmithKline must post summaries of all company sponsored observational studies or meta-analyses conducted by the company that are designed to inform the effective, safe, and/or appropriate use of its diabetes drugs; • The company post summaries of company-sponsored clinical trials of diabetes products within eight months of the primary completion date; • GlaxoSmithKline must register and post all company-sponsored clinical trials as required by federal law.</blockquote> Even more under the radar was a second, unrelated settlement, only briefly chronicled by Reuters (here <a href="http://www.chicagotribune.com/business/sns-rt-us-glaxosmithkline-settlementbre8bi14f-20121219,0,2970904.story">via</a> the Chicago Tribune): <blockquote class="tr_bq"> British drugmaker GlaxoSmithKline Plc has reached a $150 million preliminary settlement with U.S. drug wholesalers who claimed the company improperly delayed entry to the market of generic alternatives to its nasal spray Flonase, according to court documents. The settlement was reached with, among others, AmerisourceBergen Corp, Cardinal Health Inc, and McKesson Corp, who maintained that Glaxo had abused the citizen's petition process to maintain a market monopoly and overcharge for the spray by restricting access to less expensive generic versions.</blockquote> Note that while the first settlement was clearly about misleading, deceptive marketing of a relatively dangerous drug as safe, a practice that likely lead to suffering and death of some patients, the second settlement which involved an unfair business practice that likely increased the cost of care to some patients, and decreased the profits of some competitors, lead to a monetarily larger settlement. Again, these latter two settlements seem to just ice the cake of the $3 billion settlement earlier this year.  Eli Lilly Eli Lilly pleaded guilty to a misdemeanor charges and settled allegations about questionable marketing practices for its anti-psychotic drug Zyprexa for over $1 billion in 2009 (see post <a href="http://hcrenewal.blogspot.com/2009/01/what-me-worry-lilly-fined-over-zyprexa.html">here</a>).  The settlement provided some instructive information about how big pharmaceutical companies employ ghost writing to sell product (see <a href="http://hcrenewal.blogspot.com/2009/06/handbook-for-ghost-writing.html">this post</a>).  Now at the end of 2012, Eli Lilly has settled charges that it bribed government officials in countries outside of the US.  The most colorful version of this story <a href="http://online.wsj.com/article/SB10001424127887324461604578191550218188808.html">appeared</a> in the Wall Street Journal.  In summary, <blockquote class="tr_bq"> Eli Lilly & Co. agreed to pay $29.4 million in a settlement of U.S. government allegations that the drug maker's units made improper payments to foreign government officials to win business. Indianapolis-based Lilly didn't admit or deny the allegations, but agreed to have an outside consultant review the company's internal controls and its measures to comply with the U.S. Foreign Corrupt Practices Act, or FCPA. </blockquote> The colorful details were: <blockquote class="tr_bq">The SEC said in a civil complaint filed in U.S. District Court for the District of Columbia that employees of Lilly's China unit falsified expense reports to provide spa treatments, jewelry and other gifts and cash payments to government-employed doctors between 2006 and 2009. The SEC also alleged: Lilly hired a drug distributor in 2007 that paid bribes to health officials in a Brazilian state to facilitate about $1.2 million in sales of a Lilly drug to the state; Lilly's Polish unit paid $39,000 between 2000 and 2003 to a charitable foundation run by the head of a regional government health authority and dedicated to restoring a castle in Chudow, Poland; and that its Russian unit paid millions of dollars between 1994 and 2005 to offshore entities that the SEC said 'appear to have been used to funnel money to government officials' to obtain business for the Lilly unit. The SEC said Lilly didn't curtail the activities of its Russian unit for several years, even after an internal Lilly review raised questions about its use of these offshore arrangements. </blockquote> As in the previous set of settlements, no individual was charged or had to pay any penalty for authorizing, directing, or implementing any unethical actions.  Note that the alleged bribery went on in multiple different countries, suggesting a systemic problem with the operations of the company.  Note also that the allegations involved bribing doctors as well as bureaucrats. Orthofix We <a href="http://hcrenewal.blogspot.com/2012/11/phony-consulting-and-royalty-agreements.html">discussed</a> three settlements made by medical device company Orthofix only a month ago.  These involved various vivid details including bribes to physicians disguised as consulting and royalty agreements, bribes of foreign government officials disguised as chocolate, and a device sales representative turned stripper.  As best as I can tell, Orthofix just made yet another settlement, maybe not quite so picaresque.  As<a href="http://www.bloomberg.com/news/2012-12-15/orthofix-medicare-probe-settlement-accepted-by-u-s-judge-1-.html"> per Bloomberg</a>, <blockquote class="tr_bq">Orthofix International NV won court approval of a settlement of federal regulators’ claims that the maker of bone-repair products defrauded Medicare through a kickback scheme involving doctors, prosecutors said. U.S. District Judge William G. Young in Boston<a href="http://topics.bloomberg.com/boston/"></a> yesterday accepted an Orthofix unit’s offer to plead guilty to a felony count of obstructing an audit and pay a $7.6 million criminal fine....</blockquote> This settlement like some of the previous ones involved allegations of payments to doctors to induce them to use Orthofix devices. <blockquote class="tr_bq">As part of the agreement, Orthofix also will pay $32.3 million plus interest to resolve civil claims first raised in a whistle-blower’s lawsuit that the company defrauded the federal Medicare program through payments to doctors who used its bone-growth stimulators....</blockquote> This series of cases is unusual because they resulted in a guilty plea to a felony (but by a subsidiary of the company, not the company itself), and in guilty pleas by some company employees (but not apparently any penalties to top management). <blockquote class="tr_bq">Five Orthofix employees have pleaded guilty in connection with the probe, the U.S. Justice Department<a href="http://topics.bloomberg.com/justice-department/"></a> said. Thomas Guerrieri<a href="http://www.justice.gov/usao/ma/news/2012/April/GuerrieriThomasPleaPR.html" rel="external" title="Open Web Site"></a>, a company vice president, pleaded guilty to violating the federal anti-kickback statute by setting up fake consulting agreements for doctors who used the company’s products. </blockquote> Sanofi French multinational pharmaceutical corporation Sanofi-Aventis settled charges of overcharging the US Medicaid system in 2009 for over $90 million  (see post<a href="http://hcrenewal.blogspot.com/2009/05/sanofi-aventis-settles.html"> here</a>),  and of overcharging the US Medicare system in 2007 for over $190 million (see post <a href="http://hcrenewal.blogspot.com/2007/09/190-million-settlement-for-sanofi.html">here</a>).  Now it just settled charges that it gave kickbacks to doctors to induce them to prescribe its product.  <a href="http://www.bloomberg.com/news/2012-12-19/sanofi-to-pay-109-million-to-settle-false-claims-case.html">Per Bloomberg</a>, <blockquote class="tr_bq"> Sanofi,  France’s biggest drugmaker, reached a settlement to pay $109 million over allegations that its U.S. units gave doctors free doses of a medicine to win their business and subvert Medicare’s drug reimbursement system. </blockquote><blockquote class="tr_bq">Sanofi sales representatives entered into 'illegal sampling arrangements' with physicians, giving them the arthritis drug Hyalgan as kickbacks and 'promising to provide negotiated' amounts of the medication to lower its effective price in violation of the False Claims Act, the U.S. Justice Department said yesterday in a statement. 'Kickback schemes subvert the health-care marketplace and undermine the integrity of public health-care programs,” Stuart Delery,  who heads the department’s civil division, said in the statement. 'We will continue to hold accountable those who we allege are providing illegal incentives to influence the decision-making of health-care providers in federal health-care programs.'</blockquote> Again, no individual suffered any negative consequences for authorizing, directing or implementing the bad behavior in this case. Summary So here we go again, four more settlements by large, rich, well known pharmaceutical and device companies.  Most of the companies involved now have a history of recent settlements for a variety of ethical misadventures.  Most of the new settlements involved allegations of deceiving and bribing physicians. As we have noted endlessly before, <a href="http://hcrenewal.blogspot.com/search/label/legal%20settlements">legal settlements</a> like this are useful to provide documentation of how unethical the practices, particularly marketing practices of large health care organizations have become.  However, the increasing number of repeat settlers suggest that the settlements are not deterring bad behavior.  Since the fines involved are usually small compared to the revenues that can be generated by deceptive and unethical marketing of expensive drugs, and the fines are paid out of company coffers, and are thus spread out in their impact over employees and stockholders alike, they usually have no more impact than a lash with a wet noodle, maybe at best a slap on the wrist.  Since the people involved in authorizing, directing and implementing the bad behavior can likely greatly improve their "numbers" and hence generate big salaries and bonuses, but face a minimal risk of any individual negative consequences, they are likely to continue unethical practices. Given that so many of these cases involve deception and/or bribery of health care professionals, I still hope that some will get upset at the effect on their professional values to take action. Meanwhile, I repeat until blue in the face....   we will not deter unethical behavior by health care organizations until the people who authorize, direct or implement bad behavior fear some meaningfully negative consequences. Real health care reform needs to make health care leaders accountable, and especially accountable for the bad behavior that helped make them rich.

'Tis the Season for Legal Settlements: GlaxoSmithKline, Eli Lilly, Orthofix, Sanofi all Settle

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26 Dec 2012

Denying the Inconvenient Truth About Study 329

On 1BoringOldMan, Mickey, the semi-anonymous retired psychiatrist blogger, has updated the saga of <a href="http://hcrenewal.blogspot.com/search/label/Study%20329">Study 329</a>.  The manipulation of Study 329 was a central part of the US government's case against GlaxoSmithKline that was recently settled for $3 billion and resulted in three guilty pleas by the company (look <a href="http://hcrenewal.blogspot.com/2012/07/giant-gsk-settlement-provides-reminder.html">here</a> and <a href="http://hcrenewal.blogspot.com/2012/09/twilight-of-anechoic-effect-new-england.html">here</a>.) Mickey's previous voluminous series of posts on this subject are listed <a href="http://hcrenewal.blogspot.com/2012/08/continuing-dissection-of-infamous-study.html">here</a>.  He and others, most notably Dr Jon Jureidini, have attempted to get the journal that published the now widely ridiculed Study 329 retracted.  His three recent posts on the subject are: <a href="http://1boringoldman.com/index.php/2012/12/23/the-lesson-of-study-329-an-unfinished-symphony/" rel="bookmark">the lesson of Study 329: an unfinished symphony…</a>  <a href="http://1boringoldman.com/index.php/2012/12/21/hide-and-go-seek/" rel="bookmark">hide-and-go-seek… </a>  <a href="http://1boringoldman.com/index.php/2012/12/21/a-response-2/" rel="bookmark">a response… </a>  In the most recent of these, he argued, <blockquote class="tr_bq">In this particular case, there are no facts in question. It was a negative trial, declared negative by the people who did it. The paper was ghost-written and reviewed by the sponsor before any of the twenty two authors ever saw a manuscript. The science was jury-rigged to imply a positive outcome where none was supported using well-documented sleight of hand. None of that is speculative. And the article has been a centerpiece for court settlements worth billions of dollars.</blockquote> Yet, the  Journal of the American Academy of Child and Adolescent Psychiatry refused to retract the article. Mickey's opinion in the second of the posts listed above, <blockquote class="tr_bq">One can only conclude that they found this article to be an inconvenient truth, and that Dr. Andres Martin and his colleagues in the American Academy of Child and Adolescent Psychiatry believe that acknowledging that truth would do more harm than good [or maybe even found a way not to see the truth at all, though it's hard to imagine how]. Sooner or later, this whole tawdry saga is going to find its way out of the blogs and courtrooms and into the full light of day. And the question that’s going to be asked is why didn’t Medicine itself deal with the problem? Why didn’t the Journal itself retract the misinformation once they knew about it? Why didn’t the industry sponsor itself call for the retraction as part of their settlement with the DOJ? What possible reasonable reason could there be for leaving a paper that is a lie in their journal without even an expression of concern, much less a retraction? And there aren’t going to be any believable answers.</blockquote> Mickey concluded the most recent post, <blockquote class="tr_bq">The loser in this story is the American Academy of Child and Adolescent Psychiatry, and ultimately psychiatry itself…</blockquote> The longer inconvenient truths are ignored or suppressed, the more inconvenient, and hazardous they will ultimately become.  ADDENDUM (26 December, 2012) - One more post on 1BoringOldMan: <a href="http://1boringoldman.com/index.php/2012/12/26/telling-the-truth-as-a-liability/" rel="bookmark">telling the truth as a liability… </a> Its conclusion <blockquote class="tr_bq">By any criteria, the conclusion to the 2001 Keller et al article is wrong ["Paroxetine is generally well tolerated and effective for major depression in adolescents"]. That’s not the reason that some of us have been so persistent in pushing for retraction. The reason is that it was wrong at the time the article was published, and they knew it was wrong, but published it anyway. We want to make a statement about the integrity of the scientific literature. </blockquote>

Denying the Inconvenient Truth About Study 329

On 1BoringOldMan, Mickey, the semi-anonymous retired psychiatrist blogger, has updated the saga of Study 329. The manipulation of Study 329 was a central part of the US government's case against Glax…

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23 Dec 2012

Twilight of the Anechoic Effect? - New England Journal of Medicine Article Discusses Previously Taboo Topic of Bad Corporate Health Care Leadership

We have often complained of the<a href="http://hcrenewal.blogspot.com/search/label/anechoic%20effect"> anechoic effect</a>, that the issues we discuss on <a href="http://hcrenewal.blogspot.com/">Health Care Renewal</a> often do not seem to be considered topics of polite conversation.  Any discussion that might question the brilliance, integrity, dedication, or selflessness of the leaders of health care organizations seems particularly taboo.  So a major aim of this blog has been to discuss the numerous publicly available examples of leadership that is <a href="http://hcrenewal.blogspot.com/search/label/ill-informed%20management">ill-informed</a>, uncaring about or<a href="http://hcrenewal.blogspot.com/search/label/mission-hostile%20management"> hostile to</a> the values of health care professionals, incompetent, <a href="http://hcrenewal.blogspot.com/search/label/executive%20compensation">self-interested</a>, conflicted, or outright corrupt, and of governance that lacks accountability, transparency, integrity, honesty, or ethics.  We have postulated that such problems with leadership and governance are not only causes, but the major causes of the increasing dysfunction of our health care system.  That discussing these issues is simply not done in many contexts, including academic health care, medical and health care journals, and health policy fora has only accelerated health care dysfunction. The New England Journal on Punishing Health Care Fraud Therefore, I note with some surprise that the New England Journal of Medicine just published an article (online first) that implicitly challenged the leadership of some large health care organizations. [Outterson K. Punishing health care fraud - is the GSK settlement sufficient.  N Engl J Med 2012; 367: 1082 - 1085.  Link <a href="http://www.nejm.org/doi/full/10.1056/NEJMp1209249">here</a>.] The article summarized the record settling legal settlement agreed to by GlaxoSmithKline (see <a href="http://hcrenewal.blogspot.com/2012/07/giant-gsk-settlement-provides-reminder.html">this post</a>).  It noted that the company pleaded guilty to three criminal charges.  It then noted that while this was the largest recent legal settlement by a pharmaceutical company, "it would be a mistake to assume that GSK was an outlier in the global pharmaceutical and medical-device industries. Indeed, many of the major companies have settled with the Department of Justice in recent years."  It included a table of the largest pharmaceutical company settlements with the US government from 2009 to now. Based on this background, the article dared to question whether such settlements deter bad behavior: <blockquote>But questions remain about the efficacy of fines and corporate integrity agreements in deterring corporate misbehavior. The 2012 fines against Abbott Laboratories and GSK represent a modest percentage of those companies' revenue. Companies might well view such fines as merely a cost of doing business — a quite small percentage of their global revenue and often a manageable percentage of the revenue received from the particular product under scrutiny. If so, little has been done to change the system; the government merely recoups a portion of the financial fruit of firms' past misdeeds.</blockquote> Even more daring was its challenge to top executives of pharmaceutical corporations, <blockquote>One partial solution would be to impose penalties on corporate executives rather than just the company as a whole. Boston whistleblower attorney Robert M. Thomas, Jr., embraces this approach: 'GSK is a recidivist. How can a company commit a $1 billion crime and no individual is held responsible?'</blockquote>A Taboo Broken Having blogged on Health Care Renewal for nearly eight years, I recall very few, if any instances in which leaders of health care organizations were described as deserving punishment, or perhaps even guilty of crimes within large circulation medical journals, and within the New England Journal of Medicine, the most prominent US journal in particular. While discussion of misbehavior within health care organizations has slowly been seeping into the medical and health care literature, delicate phrasing has often been employed that leaves unclear whether top executives have any accountability for this behavior. (For example, while the Lancet editorial on the GSK settlement condemned "GSK's fraud," accused GSK of "actively encouraging off-label prescription," and asserted that "GSK and other drug companies have come adrift from standards of the societies they seek to serve," it never said anything about GSK's leaders or whether they in paticular had anything to do with the company's bad behavior. [Anon. Moral decaly at GSK reaps record US$# billion fine. Lancet 2010; 380: 2. Link <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961110-6/fulltext">here</a>.]) So it is a big step for the NEJM to publish an article that suggests corporate executives might deserve penalties. I hope that this publication might lead to a bit of discussion of these issues within the larger medical and health care communities, the vast majority of whom have likely never heard of this blog and may have never seen anything other than an occasional news article in local media questioning the leadership of large health care organizations. Things are Even Worse Unfortunately, I need to end with the observation that the problems are even worse than what the NEJM article implies. Legal settlements of allegations of bad behavior by large health care organizations are much more numerous than those mentioned in this article (look <a href="http://hcrenewal.blogspot.com/search/label/legal%20settlements">here </a>for examples). Many of the largest and most prestigious organizations actually have histories of multiple settlements, guilty pleas, and related legal and governmental findings. For example, look <a href="http://hcrenewal.blogspot.com/2012/08/pfizers-pforeign-pfiasco.html">here</a> for Pfizer's record, <a href="http://hcrenewal.blogspot.com/2012/09/how-many-legal-settlements-does-it-take.html">here</a> for Johnson and Johnson's record, <a href="http://hcrenewal.blogspot.com/2012/05/abbott-pleads-guilty-settles-for-16.html">here</a> for Abbott's record, and <a href="http://hcrenewal.blogspot.com/2012/06/huge-insurance-company-wellpoint.html">here</a> for Wellpoint's record. Pfizer was even found by a jury to be a racketeering influenced and corrupt organization (RICO)(see post <a href="http://hcrenewal.blogspot.com/2010/03/settlement-and-conviction-round-up.html">here</a>). Despite these records of recidivism, no leaders of these companies have paid any individual penalties, and none of these organizations have had any restructuring or leadership changes imposed. This is even more disturbing when this kid-glove treatment of misbehavior by big health care organizations is contrasted with the severe penalties imposed on individuals or leaders of small companies found guilty of health care fraud (look <a href="http://hcrenewal.blogspot.com/2012/01/unequal-justice-under-law-comparing.html">here</a>). You Heard It Here First However, in 2003 we first published documentation of individual physicians' concerns that ill-informed, incompetent, self-interested, or even corrupt leadership was threatening their core values [Poses RM. A cautionary tale: the dysfunction of American health care. Eur J Int Med 2003; 14: 123-130. Link <a href="http://www.sciencedirect.com/science/article/pii/S0953620503000293">here</a>.] Furthermore, <a href="http://hcrenewal.blogspot.com/2008/07/amerigroup-settles.html">since 2008 </a>we have been stating that corporate fines do not deter bad behavior. It is not that law enforcement does not have the power to seek penalties on individuals. As we noted <a href="http://hcrenewal.blogspot.com/2010/06/attempt-to-hold-health-care-leaders.html">here</a>, a Supreme Court case from 1943 empowered the government to seek penalties against responsible corporate officers (the "responsible corporate officer doctrine") who were in a position to stop a fraud that resulted in a guilty plea or conviction, particularly for the selling of misbranded or adulterated drugs into interstate commerce under the US Food and Drug Act.  (This was exactly the situation dealt with by the GSK settlement.)  Despite a threat made in 2010 by the chief counsel of the Inspector General's office of the US Department of Health and Human Services to use such legal authority to "get high level executives out of companies," nothing of the sort has happened. So now that it is no longer taboo to question the pretensions of some leaders of health care organizations to near divine purity, let me state <a href="http://hcrenewal.blogspot.com/2008/09/walgreen-settles.html">as I did in 2008</a>, <blockquote>As long as health care leaders can shrug off the consequences of unethical behavior merely as acceptable costs of doing business, absent any serious attempts to get health care organizations to enforce internal codes of ethical behavior or to avoid hiring ethically challenged leaders, the procession will likely continue. The effects will be continually rising costs, declining quality, shrinking access, and rising numbers of demoralized health professionals. </blockquote>As I <a href="http://hcrenewal.blogspot.com/2009/05/wellcare-settles-accepts-deferred.html">wrote in 2009</a>, <blockquote>Until bad leadership of health care organizations leads to negative consequences for those practicing it, health care leadership can be expected to continuously degrade. </blockquote>

Twilight of the Anechoic Effect? - New England Journal of Medicine Article Discusses Previously Taboo Topic of Bad Corporate Health Care Leadership

We have often complained of the anechoic effect, that the issues we discuss on Health Care Renewal often do not seem to be considered topics of polite conversation. Any discussion that might question…

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14 Sep 2012

Continuing Dissection of the Infamous Study 329

On the 1BoringOldMan blog, semi-anonymous blogger Mickey has been dissecting in detail the infamous Study 329 that GlaxoSmithKline used to promote Paxil (Seroxat, paroxetine) as safe and effective for children and adolescents, when the study data, rigorously analyzed, showed that was not the case.  Study 329 was an important part of the US Department of Justice case against GSK that resulted in a record $3 billion settlement (see this <a href="http://hcrenewal.blogspot.com/2012/07/giant-gsk-settlement-provides-reminder.html">post</a>).  The posts so far are: <a href="http://1boringoldman.com/index.php/2012/08/19/26298/">A Pretty Rotten Era   </a> <a href="http://1boringoldman.com/index.php/2012/08/21/a-movement/">A Movement</a> <a href="http://1boringoldman.com/index.php/2012/08/22/to-make-distortion-possible/">To Make Distortion Possible</a> <a href="http://1boringoldman.com/index.php/2012/08/24/the-lesson-of-study-329-the-basics/">The Lesson of Study 329: the Basics</a> <a href="http://1boringoldman.com/index.php/2012/08/25/the-lesson-of-study-329-efficacy-drift-to-trends-and-2s/">The Lesson of Study 329: Efficacy Drifts to Trends and 2s</a> <a href="http://1boringoldman.com/index.php/2012/08/26/the-lesson-of-study-329-conventions-and-protocols/">The Lesson of Study 329: Conventions and Protocols</a> <a href="http://1boringoldman.com/index.php/2012/08/29/the-lesson-of-study-329-uh-oh/">The Lesson of Study 329: Uh-oh</a> <a href="http://1boringoldman.com/index.php/2012/08/29/the-lesson-of-study-329-data-transparency/">The Lesson of Study 329: Data Transparency</a> <a href="http://1boringoldman.com/index.php/2012/08/30/the-lesson-of-study-329-the-authors/">The Lesson of Study 329: the Authors</a> This does not seem to be the end of the series, but the last post yesterday did have a striking conclusion: <blockquote>But, for the moment, I am stuck on the piece that is, to me, the most fundamental lesson from this story, and unfortunately many similar stories in the industry-funded clinical trial literature that fills our journals. The authors of this study did not function as physicians, clinicians, scientists, or even authors. Some were there because of their previous credentials. Others were there to build up future credentials. But they weren’t there to do what they presented themselves as doing. Researchers are practicing medicine too. I might be seen as naive to see this as the center of this story. If that’s the case, I’ll go to my grave being naive. Medicine has been my life, and this isn’t Medicine. There’s no place or tradition for physicians, particular physicians in high places, taking part in this kind of bullshit – particularly all the while claiming otherwise. The fact that it has been a widespread practice isn’t an excuse. That’s also an even stronger indictment. There are many principled neuroscientists working in this difficult area of medical science who’ve been tarnished by this kind of pseudoscience. There are many psychiatrists and other practitioners who’ve actually trusted these deceitful articles. And there are untold numbers of patients who’ve been medicated un-necessarily or even directly harmed by this and other capricious advise coming out of these studies – this one in particular. Rather than functioning as the advisers of ill people, these were physicians who actively participated in capitalizing on patients’ illness. </blockquote>However, despite the seriousness of these concerns, and their corroboration in the Justice Department document that pushed GSK to settle for so much money, my alma mater, Brown University, where Dr Martin Keller, the lead author of Study 329, was Chair of Psychiatry, has consistently refused to revisit the study, and consistently failed to publicly refute the accusations against Dr Keller, nor to accept them and take appropriate action.  The University supposedly conducted an internal investigation of the matter, but has not seen fit to make it public.  When <a href="http://chronicle.com/article/Academic-Researchers-Escape/133325/">asked again</a> about this, Brown's new President, Christina Paxson, referred the inquiry to the public relations people: <blockquote>'The recent announcement by the U.S. Department of Justice did not suggest that any further reviews of the paper by the university are immediately warranted,' Darlene Trew Crist said in a written response. 'We have no further statement to make at this time.'</blockquote> Given the seriousness of the allegations, and the <a href="http://www.brown.edu/about/mission">University's mission</a>: <blockquote>The mission of Brown University is to serve the community, the nation, and the world by discovering, communicating, and preserving knowledge and understanding in a spirit of free inquiry, and by educating and preparing students to discharge the offices of life with usefulness and reputation. </blockquote>the logic of the administration's refusal to have a public discussion of this case escapes me. As I have <a href="http://hcrenewal.blogspot.com/2008/09/brown-university-student-journalists.html">said before </a>(in 2008!), the appearance of continued stonewalling, now going on for years, can easily be interpreted to imply that the institution has something really big and bad to hide. Also see comments by Alison Bass <a href="http://alison-bass.com/blog/2012/08/why-academic-researchers-involved-in-fraudulent-paxil-study-escape-scrutiny/">on the Alison Bass blog</a>, and by Dr Howard Brody <a href="http://brodyhooked.blogspot.com/2012/08/ghostwriting-still-no-consequences-for.html">on the Hooked: Ethics, Medicine and Pharma blog</a>. ADDENDUM (4 September, 2012) - There have been two additional posts on the 1BoringOldMan blog on Study 329: <a href="http://1boringoldman.com/index.php/2012/09/02/the-lesson-of-study-329-the-hurdles/" rel="bookmark">the lesson of Study 329: the hurdles… </a> <a href="http://1boringoldman.com/index.php/2012/09/04/the-lesson-of-study-329-naked-emperors-fractious-queens/" rel="bookmark">the lesson of Study 329: naked Emperors, fractious Queens… </a> ADDENDUM (4 September, 2012) - See also <a href="http://alison-bass.com/blog/2012/09/calls-for-action-against-authors-of-fraudulent-paxil-study-are-getting-louder/">this post</a> on the Alison Bass blog. ADDENDUM (5 September, 2012) - See <a href="http://www.pharmalot.com/2012/09/controversial-paxil-study-author-retires-from-brown/">this post</a> on the retirement of Dr Keller by Ed Silverman on PharmaLot. ADDENDUM (10 September, 201) - See the final two posts in the 1BoringOldMan series: <a href="http://1boringoldman.com/index.php/2012/09/06/the-lesson-of-study-329-were-only-as-sick-as-our-secrets/" rel="bookmark">the lesson of Study 329: “we’re only as sick as our secrets”… </a> <a href="http://1boringoldman.com/index.php/2012/09/08/the-lesson-of-study-329-epilogue/" rel="bookmark">the final lesson of Study 329: epilogue… </a> His conclusion in the next to last post of the series: <blockquote>Something terrible happened in psychiatry, an alliance between the pharmaceutical industry and a number of our leaders who allowed their academic credentials to be used for commercial purposes. It happened on a large scale, and in the process shamed all of us, whether we were involved or not. Many of the people we looked to to guide us fell into the role of key opinion leaders – a marketing term that meant that they could influence what we did and how we practiced. And in that new role, medical degrees, academic positions, the methods of science, and psychiatric experience became little more than marketing tools in a commercial campaign. Such was the case with Study 329 – an article that has become exemplary because it is now so painfully well known – a symbol for the failings of an era. It needs to be retracted simply because it was wrong on purpose – and we all know it. And yet no involved person, institution, or organization highlighted in that last paragraph has swallowed their pride, or guilt, or denial, or arrogance and called for retraction.</blockquote>[Italics and bold typeface added for emphasis]

Continuing Dissection of the Infamous Study 329

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31 Aug 2012

Giant GSK Settlement Provides Reminder of the Pervasiveness of Stealth Marketing

The latest  and biggest legal settlement involving health care to hit the news, that of GlaxoSmithKline (GSK) and the US government, has many familiar elements. As <a href="http://www.nytimes.com/2012/07/03/business/glaxosmithkline-agrees-to-pay-3-billion-in-fraud-settlement.html">summarized by the New York Times</a>, <blockquote>In the largest settlement involving a pharmaceutical company, the British drugmaker GlaxoSmithKline agreed to plead guilty to criminal charges and pay $3 billion in fines for promoting its best-selling antidepressants for unapproved uses and failing to report safety data about a top diabetes drug, federal prosecutors announced Monday. The agreement also includes civil penalties for improper marketing of a half-dozen other drugs. </blockquote> As was the case for nearly every other <a href="http://hcrenewal.blogspot.com/search/label/legal%20settlements">legal settlement</a> we have discussed, <blockquote>No individuals have been charged in any of these cases.</blockquote>Thus, how well even such a large settlement will deter future wrong-doing is not clear. Nonetheless, the documents released with it provide good documentation about how pervasive systematic, deceptive stealth marketing campaigns have become in health care.  In particular, the <a href="http://www.justice.gov/opa/documents/gsk/us-complaint.pdf">official "complaint" filed by the US Department of Justice</a> emphasized all these elements in the stealth marketing of paroxetine (Paxil, Seroxat in the UK) to adolescents. Manipulation of Clinical Research We have frequently discussed how health care corporations, particularly pharmaceutical, biotechnology and device companies, now sponsor  the majority of clinical research.  Their control of the design, implementation, analysis and dissemination of clinical research allows <a href="http://hcrenewal.blogspot.com/search/label/manipulating%20clinical%20research">manipulation</a> that increases the likelihood that the results will be favorable to their vested interests, usually the products and services they sell.  We have previously discussed the manipulation of Study 329 to promote the marketing of Paxil (look <a href="http://hcrenewal.blogspot.com/2008/04/selective-reporting-of-study-329.html">here </a>and <a href="http://hcrenewal.blogspot.com/2008/09/brown-university-student-journalists.html">here</a>).  However, the US DOJ document makes these concerns more official.  It included: Manipulation of Study Endpoints Study 329 was a randomized controlled trial of Paxil vs imipramine vs placebo for depression in adolescents. The two primary endpoints pre-specified to the US Food and Drug Administration were "the degree to which a patient's Hamilton Rating Scale for Depression ('HAM-D') total score changed from baseline"; and "the patient's 'response' to medication, as defined as (a) a 50% or greater reduction in the patient's HAMD-D score, or (b) a HAM-D score of less than or equal to 8." However, initial analysis by GSK failed to show that Paxil improved either of these two end-points. The company concluded "it would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of [Paxil]." So the analysis emphasized secondary outcomes, the "Study 329 investigators later added several additional efficacy measures not specified in the protocol. Paxil separate statistically from placebo on certain of these measures." Adding numerous post-hoc measures increased the likelihood of finding a difference on at least one due to chance alone. Manipulation of Data Initial analysis of the data suggested that patients given Paxil experienced 11 serious adverse events, including five that appeared related to suicidal ideation or action. When the FDA later reexamined the data, "upon closer examination the number of possible suicide-related events among the Study 329 Paxil patients increased beyond the five patients GSK described in the JACAAP article as having 'emotional lability.' While collecting saftey information for the FDA, GSK admitted that there were four more possible suicide-related events among Paxil patients in Study 329. In addition the FDA later identified yet another possible suicide-related event in the Study 329 Paxil patients, which was also not among the 11 serious advents listed in the JAACAP article. Thus, altogether, 10 of the 93 Paxil patients in Study 329 experienced a possible suicidal event, compared to one in 87 patients on placebo. This is a fundamentally different picture of Paxil's pediatric safety profile than the one painted by the JAACAP article...."  Manipulation of Dissemination The report describing the results of Study 329 (Keller MB, Ryan ND, Strober M et al.  Efficacy of paroxetine in the treatment of adolescent major depression: a randomized controlled trial.  J Am Acad Child Adolescent Psychiatry 2001; 40: 762-772.  Link <a href="http://www.justice.gov/opa/documents/gsk/complaint-ex2.pdf">here</a>. ) was written under the control of GSK. "In April 1998, GSK hired Scientific Therapeutics Information, Inc (STI) to prepare a journal article about Study 329. GSK worked closely with STI on the article by providing a draft clinical report to 'serve as a template for the proposed publication.'" The published report of Study 329 "mischaracterized the results." "Although the ... article identified the study's two primary endpoints in the abstract, the article did not explicitly state that Paxil failed to show superiority to placebo on either of the primary efficacy measures." Also, "the article did not explicitly identify the two protocol-specified primary outcome measures - or that Paxil failed to show superiority to placebo on these two measures. Instead the article claimed that there were eight efficacy measures and that Paxil was statistically superior to placebo on four of them." In addition, "while the article listed the five protocol-defined secondary endpoints, the text of the article omitted any discussion regarding three of the secondary measures on which Paxil failed to statistically demonstrate its superiority to placebo and instead focused on the five secondary measures that GSK added belatedly and never incorporated into the Study 329 protocol. The article claimed that these finve secondary measures had been identified 'a priori,' therefore incorrectly suggesting that all secondary endpoints had been part of the original study protocol." In other words, the final published articles contained multiple outright falsehoods about the drug's efficacy that exaggerated that efficacy. Furthermore, initial analysis showed that patients given Paxil had more serious adverse events than others. An initial draft of the study article stated, "serious adverse events occurred in 11 patients in the paroxetine group, 5 in the imipramine group, and 2 in the placebo group." These included "headache during down-titration(1 patient), and various psychiatric events (10 patients): worsening depression (2); emotional lability (e.g., suicidal ideation/ gestures, overdoses), (5); conduct problems or hostility (e.g., aggressiveness, behavioral disturbance in school) (2); and mania (1)." As noted above, the number of suicide related events was actually double that noted in this draft as "emotional lability."  However, the published version of the report "falsely state[d] that only one of the 11 serious adverse events in Paxil patients was considered related to treatment...."  Nor did it mention the true number of events related to suicidal ideation or action. The article only "listed at most five possibly suicidal events among Paxil patients, brushed those off as unrelated to Paxil, and conclude that treating children with Paxil was safe." Later, GSK marketing materials described the results of the study thus, <blockquote>This 'cutting-edge,' landmark study is the first to compare efficacy of an SSRI and a TCA with placebo in the treatment of major depression in adolescents. Paxil demonstrates REMARKABLE Efficacy and Safety in the treatment of adolescent depression."</blockquote>Thus the conrol exerted by GSK over the published article, despite its apparent academic authorship, enabled it to promote a drug that was not efficacious and had major adverse events as remarkably safe and effective, a totally deceptive result that would mislead any health care professional who used the article to guide clinical practice.  Suppression of Clinical Research GSK sponsored two other studies of Paxil in pediatric populations, Studies 377 and 701. As stated in the Department of Justice's Criminal Complaint against GSK, <blockquote>GSK Did Not Publicize the Results of Studies 377 and 701 43. GSK learned the results of Study 377 in 1998 and the results of Study 701 in 2001. Paxil failed to demonstrate efficacy on any of the endpoints of either study. 44. GSK did not hire a contractor to help write medical articles about the results of Studies 377 and 701, as it had with Study 329. 45. GSK did not inform its sales representatives about the results of Studies 377 and 701.</blockquote>Thus, GSK managed to conceal the fact that the majority of the studies it sponsored about Paxil used for adolescent patients showed no evidence that the drug worked, again seriously distorting the evidence-base on which clinicians made decisions, and doubtless leading to the use of a dangerous, ineffective drug by numerous vulnerable patients. Bribing Physicians to Prescribe <blockquote>GSK's sales representative reflected in their call notes their use of money, gifts, entertainment and other kickbacks to induct doctors to prescribe GSK drugs.... </blockquote> One really creative way to pay physicians to be exposed to marketing: <blockquote>For example, in or about 2000 or 2001, GSK used 'Reprint Mastery Training Programs' or 'RMTS' to further promote drugs by purporting to pay physicians to train sales representative to review reprints of studies. Although the training was purportedly for the representatives, in fact, the sales force was already familiar with the materials. GSK typically paid physicians $250 to $500 to review the reprints.</blockquote>Thus GSK simply paid physicians to use its drug, a practice characterized as kickbacks in the official complaint.  An <a href="http://www.guardian.co.uk/business/2012/jul/03/glaxosmithkline-fined-bribing-doctors-pharmaceuticals">article in the Guardian </a>noted that the US Attorney involved in the case put it even more bluntly, <blockquote>The sales force bribed physicians to prescribe GSK products using every imaginable form of high-priced entertainment, from Hawaiian vacations [and] paying doctors millions of dollars to go on speaking tours, to tickets to Madonna concerts.</blockquote> Use of Key Opinion Leaders as Disguised Marketers <blockquote>GSK also created a group of national 'key opinion leaders' ('KOLs') who were paid generous consulting fees. GSK selected many of these physicians based on their prescribing habits and influence within the community and used the speaker fees paid to these physicians to induce and reward prescribing of GSK's products. GSK used these individual to communicate marketing messages focused on the drug's marketing campaigns at the time, including off-label uses. Some physicians on GSK's speaker's board have been paid more than a million dollars for speaking on behalf of the company and recommending its drugs.</blockquote> Thus key opinion leaders were paid specifically to market drugs, and as a reward, a bribe for prescribing drugs. Consulting Fees as Kickbacks In general, <blockquote>In order to induce physicians to prescribe and recommend its drugs, GSK paid kickbacks to health professionals in various forms, including speaking or consulting fees, travel, entertainment, gifts, grants, and sham advisory boards, training,....</blockquote> In particular, <blockquote>During 2000 and 2001 at least, GSK also utilized events termed 'advisory boards' or consultant meetings and forums to disseminate its promotional message. Although these boards were purportedly composed of 'thought leaders' for the purpose of obtaining advice from the physicians, in fact, the 'advisory boards' were little more than promotional events coupled with financial inducement to prescribing and influential physicians.</blockquote> Also, <blockquote>GSK typically paid the physician between $250 and $750 to attend each local 'advisory' meeting. The payments did not reflect the value of services. The physician was not required to do anything but show up. GSK had no legitimate business reason to hire thousands of 'advisors' to 'consult' with the company about a single drug. </blockquote> Manipulation of Continuing Medical Education <blockquote>GSK also used so-called CME and CME Express programs and other sham training for marketing purposes, and to promote off-labe uses for the GSK prescription drugs.</blockquote> Furthermore, <blockquote>These CME programs purported to be independent eduaction free of company influence, but in fact functioned as GSK promotional programs disguised as medical education. GSK maintained control and influence over the purportedly independent CME programs through speaker selection, and influence over content and audience, among other things. Although third party vendors were usually also involved, they served only as artificial 'firewalls' that did not insulate the program from GSK's influence.</blockquote> Summary The legal documentation of the GSK settlement demonstrated how one drug company used an integrated, systematic campaign incorporating deception and bribery to sell drugs. Its elements included manipulation and suppression of the clinical research it sponsored, paying key opinion leaders to be disguised drug marketers, outright payments to physicians to prescribe drugs, and manipulation, again using payments to physicians, of supposedly independent continuing medical education.  Note that while I summarized the elements of the stealth marketing campaign to sell Paxil, particularly for use in pediatric patients, the US government complaint also documents similar activities used to sell other drugs.  Furthermore, other <a href="http://hcrenewal.blogspot.com/search/label/stealth%20marketing">stealth marketing campaigns</a> have come to light through legal action, and many other instances of <a href="http://hcrenewal.blogspot.com/search/label/manipulating%20clinical%20research">manipulation</a> and <a href="http://hcrenewal.blogspot.com/search/label/suppression%20of%20medical%20research">suppression</a> of clinical research, use of <a href="http://hcrenewal.blogspot.com/search/label/key%20opinion%20leaders">KOLs</a> as disguised marketers, <a href="http://hcrenewal.blogspot.com/search/label/kickbacks">kickbacks</a> and bribes, and manipulation of <a href="http://hcrenewal.blogspot.com/search/label/continuing%20medical%20education">CME</a> have been documented. This means that any claims that: - commercially sponsored clinical research provides clear, unbiased data that should drive clinical decisions - health care professionals and academics paid as consultants by commercial health care firms are not influenced by these payments, and can provide clear, unbiased opinions - commercially sponsored medical education provides clear, unbiased teaching unfortunately must be viewed with extreme skepticism. This is particularly unfortunate given that most clinical research is now supported by commercial sponsors, and the majority of influential academics in medicine get some form of payments from the health care industry (look <a href="http://hcrenewal.blogspot.com/2007/10/medical-school-leaders-conflicts-of.html">here</a>). Of course, there are some physicians who consult for commercial firms who actually provide clinical or scientific advice or assistance, and some commercially sponsored activities are honest. But we must wonder what garden path all those advocates for increasing industry "collaboration" to promote "innovation," and who regard conflicts of interest as "inevitable" and "manageable" are taking us down (e.g., look <a href="http://hcrenewal.blogspot.com/2012/02/logical-fallacies-in-defense-of.html">here</a> and <a href="http://hcrenewal.blogspot.com/2011/11/if-medical-school-is-just-part-of.html">here</a>). Although the current settlement will require a huge payment, as I have said many times before (as early as 2008, <a href="http://hcrenewal.blogspot.com/2008/07/amerigroup-settles.html">here</a>), do not expect such settlements to deter future bad behavior like that listed above.  The cost of the settlement will actually be spread among all company shareholders, all company employees, and likely patients and taxpayers.  However, the settlement will entail no specific negative consequences to the people who authorized, directed, or implemented the bad behavior.  In particular, executives whose remuneration was swollen by proceeds from the sales of affected drugs, and the health care professionals who willingly accepted what the US Attorney called bribes will not pay any sort of penalty.  The bad behavior listed above was doubtless personally very profitable for some people.  Unless people who indulge in such behavior face the possibility of penalties worse than their expected gains, expect such bad behavior to continue. In fact, as the New York Times reported, <blockquote>critics argue that even large fines are not enough to deter drug companies from unlawful behavior. Only when prosecutors single out individual executives for punishment, they say, will practices begin to change. 'What we’re learning is that money doesn’t deter corporate malfeasance,' said Eliot Spitzer, who, as New York’s attorney general, sued GlaxoSmithKline in 2004 over similar accusations involving Paxil. 'The only thing that will work in my view is C.E.O.’s and officials being forced to resign and individual culpability being enforced.' </blockquote> True health care reform would strive to eliminate important conflicts of interest affecting clinical research and medical education.  Specifically, it would prevent corporations that sell health care products or services from controlling clinical research meant to evaluate these products or services.  It would seek to eliminate serious conflicts of interest affecting health care professionals.  Finally, it would prevent vested interests from controlling medical education.  Not that I expect any such reform in the near future, it would be too threatening to those who have personally benefited from the current system. Hat tip to Dr Howard Brody whose Hooked: Ethics, Medicine and Pharma blog <a href="http://brodyhooked.blogspot.com/2012/07/inside-paxil-study-329-courtesy-justice.html">scooped me </a>on the details of the settlement relevant to study 329. ADDENDUM (11 July, 2012) - see also <a href="http://1boringoldman.com/index.php/2012/07/06/another-shot/">this post</a> on the 1BoringOldMan blog.

Giant GSK Settlement Provides Reminder of the Pervasiveness of Stealth Marketing

The latest and biggest legal settlement involving health care to hit the news, that of GlaxoSmithKline (GSK) and the US government, has many familiar elements. As summarized by the New York Times,In …

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05 Jul 2012

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