Turn That Door Around - A Physician Substantially Tied to the Pharmaceutical Industry Nominated to Run the FDA

It seems to be the season of the revolving door in health care.  The latest version got some media attention, because it involves one of the most important health care leadership positions in the US government, the Director of the Food and Drug Administration (FDA).  However, the case actually seems much more serious than what the media has recently reported.

The Basics

For an introduction, we turn to the Wall Street Journal from September 15, 2015:

President Barack Obama plans to nominate the prominent cardiologist and medical researcher Robert Califf as the next commissioner of the Food and Drug Administration, the White House said Tuesday.

Dr. Califf had been named the FDA’s deputy commissioner for medical products and tobacco—effectively the No. 2 post—in February. He joined the FDA from Duke University, where he had served as a professor of medicine, a leading pharmaceutical researcher and the vice chancellor for clinical and translational research.

The new nomination got some rave reviews. For example, from the WSJ article,

Francis Collins, director of the National Institutes of Health and a scientist who has worked with Dr. Califf for years, called this 'a fantastic nomination.'

Then this in the NY Times (Sept 15, 2015):

'He’s never forgotten that at his core he’s a doctor, and he cares deeply about providing evidence to help people take better care of patients,' said Dr. Robert Harrington, professor and chairman of the department of medicine at the Stanford University School of Medicine, who worked with Dr. Califf at Duke.

Also, a MedPage Today article was entitled, "Califf Nomination for FDA Chief Gets Most High Marks," and included such testimonials as,

'He has a very good understanding of industry and academia, and think that will serve him well,' Caleb Alexander, MD, co-director of the Johns Hopkins Center for Drug Safety and Effectiveness in Baltimore, told MedPage Today....

Also, this from Dr Harlan Krumholz,

He's a broad thinker and a very creative and visionary individual. He will be an outstanding choice.

And this from Dr Sanjay Kaul,

I can't think of a more qualified person than Dr. Califf to lead the FDA at the present time. He is an accomplished leader in cardiovascular disease research whose work has resulted in therapies that save lives and improve the quality of life for millions of patients.

Is it time to break out the confetti yet?

Conflicts of Interest a Fly in the Ointment?

The only fly in the ointment was the matter of Dr Califf's ties to industry. The WSJ article included,

Diana Zuckerman, president of the National Center for Health Research, a Washington-based group focusing on medical-product safety, questioned his ties to the drug industry.

'Dr. Califf’s expertise and his close ties to the pharmaceutical industry are both well-known,' she said. 'His ties to industry have been a source of great concern to public-health experts when he was previously considered for FDA commissioner, and those ties raise important questions about this nomination.'

The MedPage Today article noted that Public Citizen's Health Research Group stated,

'During his tenure at Duke University, Califf racked up a long history of extensive financial ties to multiple drug and device companies, including Amgen, Astra-Zeneca, Eli Lilly, Johnson & Johnson, Merck Sharpe & Dohme and Sanofi-Aventis, to name a few,' Michael Carome, MD, the group's director, said in a statement. 'Strikingly, no FDA commissioner has had such close financial relationships with industries regulated by the agency prior to being appointed.'

The MedPage Today article, however, then went on to undermine those concerns, implying that only fringe people like those at Public Citizen were really worried. 

Most experts contacted by MedPage Today seemed to think Califf would not have a problem getting Senate confirmation. 'I expect him to be confirmed," said [Dr. Steven] Nissen. 'He is very well liked by people ... in both parties, and I would expect the nomination to go well.'

'All signals suggest that Dr. Califf is well-respected on both sides of the political aisle,' Jay Wolfson, DrPH, JD, senior associate dean at the University of South Florida's Morsani College of Medicine, in Tampa, said in an email.

'There are some who believe his relationship with [the drug industry] may be a problem, but most see it as a value-added factor in building a functional, more streamlined relationship with the industry in order to improve the speed with which truly effective and quality drugs and devices are made available, mitigate the excessive costs associated with pharmaceuticals, and influence policies and practices intended to improve health status.'

Note that the experts were not all named, or their expertise described, the first two paragraphs were really about Dr Califf's political support, and the third paragraph clearly reflected the views of someone who thought that the FDA needs to have a lighter regulatory touch. 

There was additional reporting about Dr Califf's conflicts of interest, but again with the effect of minimizing their importance.  The Wall Street Journal published a second article on September 18, 2015 which first reported,

From 2009 through early 2015, Dr. Califf received consulting fees of roughly $205,000 from companies including Johnson & Johnson, Merck & Co., GlaxoSmithKline PLC and one medical-device maker, records show. The payments are documented by the federal Open Payments database, and PharmaShine, a database of pharmaceutical disclosures operated by Obsidian Healthcare Disclosure Services LLC. Drug makers spent an additional $21,000 on travel, meals and other expenses for Dr. Califf, data show.

But the article provided this counterpoint,

Kevin Griffis, a spokesman for the Department of Health and Human Services, said Dr. Califf had ceased all work with drug makers once he was hired by the FDA and that he has gone through a rigorous screening process for potential conflicts of interest. Mr. Griffis said Dr. Califf had donated all the consulting fees he has received since the mid-2000s to nonprofit groups.

'Dr. Robert Califf’s professional career has been dedicated to advancing biomedical research, including the rigorous evaluation of the safety, efficacy and appropriate use of both new medical products and those already on the market,' said Mr. Griffis, assistant secretary for public affairs at HHS.

Note that Dr Califf already is at the FDA, in a position that I do not believe required Senate confirmation.  It is striking, however, how the agency's own public relations people have jumped to his defense now as a nominee who has to be confirmed by the Senate.  However, I suppose that had Dr Califf donated all this fees to a local soup kitchen, they could not be called much of a conflict of interest.  But Mr Griffis said "nonprofit groups," without specification, not "soup kitchens." And continue reading to find out more. 

A simultaneous NY Times article enlarged a bit on Dr Califf's industry relationships,

He has written scientific papers with pharmaceutical company researchers, and his financial disclosure form last year listed seven drug companies and a device maker that paid him for consulting and six others that partly supported his university salary, including Merck, Novartis and Eli Lilly. A conflict-of-interest section at the end of an article he wrote in the European Heart Journal last year declared financial support from more than 20 companies.

However the NYT article also quoted Mr Griffis about the donations to "nonprofits," and added,

A résumé studded with industry funding is not unusual in academic medicine, Dr. Califf’s supporters note. Doctors are paid consulting fees all the time, and universities routinely conduct clinical trials on behalf of companies. Those contracts help support university researchers’ salaries, a standard practice. Many emphasize that it does not imply an inherent conflict.

His supporters contend that Dr. Califf’s vast experience in the clinical science world could be a major asset in his new post.

Furthermore,

Supporters and former colleagues say Dr. Califf’s background makes him perfectly suited to the job of commissioner. He has spent years improving the way clinical trials are conducted, coming up with groundbreaking trial designs for medicines against blood clots.

'His integrity in scientific matters is impeccable, and his innovation in clinical trial design is legendary,' said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic, who has been an outspoken critic of both the F.D.A. and drug companies.

Even better,

Dr. Califf is often in the gym on the StairMaster before 6 a.m., said a former colleague at Duke, Dr. Adrian Hernandez. He often invites younger doctors to join him in golf and has a passion for Duke basketball that he expresses by wearing the team colors on game days.

How could anyone criticize a man who is at the gym at 6 AM?

More seriously, note that while the recent reporting may bring up questions about Dr Califf's conflicts of interest in terms of financial relationships with drug, device and biotechnology companies when he was on the Duke faculty, all the reporting also included passages minimizing the importance of these conflicts.  To minimize the issue of conflicts of interest, articles cited unnamed experts, suggesting the logical fallacy of an appeal to authority; noted that the financial ties that were criticized are standard practice in academic health care, suggesting the logical fallacy of an appeal to common practice.  The articles also cited Dr Califf's positive attributes which may have been relevant to his work at the FDA, like knowledge of research, but were not related to the question of conflicts of interest. This suggests another appeal to authority, or something of a reverse ad hominem (pro hominem?) fallacy.  It seems odd that what appear to be straightforward journalistic reports of a presidential nomination included such attempts to defend the candidate.  Note further that many of these logical fallacies appeared not in quotes from Dr Califf's supporters, but in text apparently written by journalists (e.g., "industry funding is not unusual," "in the gym on the Stairmaster," etc.)

Nonetheless, this is the state of play as of this moment.  The thrust of the media coverage suggested that Dr Califf is a brilliant physician and researcher, and while he as some ties to industry, they do not amount to much of a problem, except in the eyes of the likes of Public Citizen.


If one digs deeper, however, there is more. When Dr Califf was appointed to his current FDA position in February, 2015, and years earlier when his name was first mentioned as a possible candidate to run the FDA, evidence appeared that his ties to pharmaceutical, biotechnology and device companies were much more serious than what the recent accounts suggested.  

Where Does the Money from Industry Sponsored Research Grants Go? 

The recent coverage of Dr Califf's nomination in the NY Times dismissed his multiple corporate research grants as common practice.  Yet in the TIME coverage of  his original appointment to the FDA in February, 2015, this reminder of the significance of corporate sponsored research grants appeared.

Califf says his salary is contractually underwritten in part by several large pharmaceutical companies, including Merck, Bristol-Myers Squibb, Eli Lilly and Novartis.

Note that apologists for physician and academician interaction with industry often claim that industry funding of research grants that does not go directly to individuals does not cause important conflicts of interest. In one sentence, however, this article underlined how these grants support academic salaries, and hence lead to the dependency that is at the heart of conflicted relationships.

As we posted in 2007, academic medical institutions now depend on "external," including corporate research funding to support their research faculty's salaries, and via "overhead," their overall budgets.  Dr Lee Goldman, then Dean and Executive Vice President at Columbia University, called faculty who bring in a lot of grant money "tax payers," who earn gratitude, and likely bonuses and perks.  Thus Dr Califf's multiple large corporate research grants cannot be completely dismissed as conflicts of interest. 


A More Extensive List of Industry Relationships

Furthermore, a relatively obscure February, 2015, report from MDDIOnline noted that Dr Califf had more industry relationships than were reported this month,

Conflict of interest disclosures dating back to 2007 made public by the DCRI show that Califf has been paid for consulting or other services provided to a number of medical device pharmaceutical, and biotech companies, including Medtronic, Acumed, Bayer Healthcare, Merck, Novartis, Roche, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly & Co. Califf also disclosed that he held equity in two pharmaceutical companies—Boulder-based N30 Pharmaceuticals and South San Francisco, CA-based Portola Pharmaceuticals—as recently as 2014. Califf retired from Portola’s board of directors January 26, according to a press release from the company.

A somewhat more obscure commentary by Martha Rosenberg in OpEdNews provided even more extensive listings of Dr Califf's industry relationships. And it suggested having a look at the disclosures he has made in the past in medical journal articles. A statement in a 2013 JAMA commentary was particularly telling,

Dr Califf receives research grants that partially support his salary from Amylin, Johnson & Johnson, Scios, Merck/Schering-Plough, Schering-Plough Research Institute, Novartis Pharma, Bristol-Myers Squibb Foundation, Aterovax, Bayer, Roche, and Lilly; all grants are paid to Duke University. Dr Califf also consults for TheHeart.org, Johnson & Johnson, Scios, Kowa Research Institute, Nile, Parkview, Orexigen Therapeutics, Pozen, WebMD, Bristol-Myers Squibb Foundation, AstraZeneca, Bayer/Ortho-McNeil, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Gilead, GlaxoSmithKline, Li Ka Shing Knowledge Institute, Medtronic, Merck, Novartis, sanofi-aventis, XOMA, University of Florida, Pfizer, Roche, Servier International, DSI-Lilly, Janssen R&D, CV Sight, Regeneron, and Gambro; all income from these consultancies is donated to nonprofit organizations, with most going to the clinical research fellowship fund of the Duke Clinical Research Institute. Dr Califf holds equity in Nitrox LLC, N30 Pharma, and Portola.

These lists of corporations from which Dr Califf got salary support and consulting fees are much longer than previous lists.  He acknowledged 13 commercial research sponsors, and consulted for 32 organizations, most of which were pharmaceutical companies.  Again, given that the salary support and overhead likely supplied by corporate research grants do suggest conflicts of interest, Dr Califf may have had many more of these sorts of conflicts than current reports implied  

A Seat on a Pharmaceutical Company Board of Directors

Note that the MDDIOnline article mentioned that Dr Califf was a member of the board of directors of Portola Pharmaceuticals. That was a significant source of income.  According to the Portola Pharmaceuticals 2015 proxy statement, Dr Califf received $259,623 in cash and stock options from the company in 2014.  I cannot find anything to suggest that this payment did not go directly to him.  This position, and the money it paid were not mentioned in the recent coverage. That payment alone seems to represent a major conflict of interest.

However, being on the board of directors of a health care corporation presents a deeper conflict than that produced by a simple payment of money or stock options, no matter how large. In 2006, we discussed corporate directorships as a new and important species of conflict of interest for medical academics.  As we have previously posted, corporate directors have fiduciary responsibilities to the company and its shareholders to support its financial success.  They are supposed to "demonstrate unyielding loyalty to the company's shareholders" [Per Monks RAG, Minow N. Corporate Governance, 3rd edition. Malden, MA: Blackwell Publishing, 2004. P.200.]   Thus corporate directors have a much more significant commitment to the corporation than do corporate consultants, or researchers supported by corporate grants. 

Where Did Those Donated Consulting Payments Go?

Also note that the disclosure statement in the JAMA article mentioned that most of the consulting payments Dr Califf received went to the clinical research fellowship of the Duke Clinical Research Institute (DCRI).  Dr Califf was the first director of DCRI, 

So, while Dr Califf apparently did donate the consulting fees to a non-profit organization, that organization actually was part of Duke, and an organization that Dr Califf once led. It appears likely that Dr Califf benefited at least indirectly in terms of institutional gratitude and reputation from these consulting fees that he donated to his own institution.  So it appears that Dr Califf's donations of his consulting fees did not reduce the conflicts of interest generated by these fees to the extent suggested by the current FDA spokesperson and current media reports. 

Payments for "Educational Activities" 

Finally, perusal of disclosures of Dr Califf's commercial relationships made by the Duke Clinical Research Institute for the years 2010-2015 showed that he received payments for "educational activities" in 2011 from Amylin.  Information about earlier years is not available on this site, but in 2009, Dr Daniel Carlat wrote this about Dr Califf's then rumored candidacy for leadership of the FDA in the Carlat Psychiatry Blog,

look at these industry disclosures. He took money—lots of money--from 18 different pharmaceutical or device firms. Most of this was not for research, but for consulting and speaking, including CME. If Dr. Califf believes that it is ethical for physicians to help drug companies market their products, that’s his own business. But to elevate him to a position in which he is the country’s chief watchdog over unsafe medications and foods seems a dangerous move. With money from 18 drug companies padding his bank account, he will presumably spend most of his FDA career recusing himself from crucial decisions. Not a good idea.

There has been no mention of Dr Califf being a paid speaker for pharmaceutical companies in any of the recent reporting.  Dr Carlat implied that Dr Califf was paid to speak to further marketing objectives of pharmaceutical companies, that is, was giving "drug talks."  Since the publication of "Dr Drug Rep" in the New York Times in 2007, authored by Dr Carlat, the public has learned that such talks mainly include content provided by the pharmaceutical companies, and are meant by the companies as marketing exercises.  From that case we also learned that physicians who deviate from the marketing message do not last long on speakers' bureaus.  (See posts here and here.)

Paid speakers may be regarded by pharmaceutical companies as paid "key opinion leaders," KOLs, who serve a marketing function in the guise of academics. As noted here and here, the companies buying their services may believe they have bought the services of sales people.    Evidence about key opinion leaders actually performing like marketers has come from documents revealed during litigation (e.g., see this recent example of a huge monetary settlement made of charges that GlaxoSmithKline, a major multinational drug company committed fraud among other things, and in the course of its unethical activities used key opinion leaders as marketers).   Also, see the Neurontin marketing plan (see post here), and the Lexapro marketing plan (see post here) for examples of how company keaders view key opinion leaders as marketers.

So the revelation that Dr Califf received corporate payments for "education" suggests a bigger commitment to corporate marketing objectives than has previously been revealed.  

Summary

So, looking at not only current media reports, but media reports from earlier this year, and also proxy statements, the fine print of journal articles, and old blog posts, it appears that Dr Robert Califf really did have very substantial financial interactions with the drug, device and biotechnology industry.  These interactions likely underwrote his salary and his standing with the leaders of his former employer, Duke University.  Dr Califf seemed to be a paid speaker for drug companies on at least two occasions, suggesting that the companies may have put him in a covert marketing role, or viewed him as a paid key opinion leader.  Finally,  Dr Califf served on the board of directors of one drug company, a much deeper commitment than being a sponsored researcher or consultant.

Thus Dr Califf really appears to be one of the most, if not the most drug, device and biotechnology industry connected individual ever nominated to lead the agency that is the most important regulator of the US drug, device and biotechnology industry.  Some of his connections, particularly his previous membership on a pharmaceutical company board, and his previous roles as a paid pharmaceutical speaker, suggested not only financial relationships, but commitments to companies' financial and marketing goals.  These appear to be major conflicts of interest vis a vis Dr Califf's current leadership position at the FDA, and his nomination to be the ultimate leader of this regulatory agency.  This is the revolving door writ large.

As we have said very recently,  the revolving door can be veiwed as a species of conflict of interest.  Government officials who can look forward to extremely lucrative employment in health care industry may be much more inclined to seem friendly to the industry while in office.  Government officials who just came from industry are likely to maintain their industry mindset and be mindful of their industry friends.

Worse, some experts have suggested that the revolving door is in fact corruption.  As we noted here, the experts from the distinguished European anti-corruption group U4 wrote,

The literature makes clear that the revolving door process is a source of valuable political connections for private firms. But it generates corruption risks and has strong distortionary effects on the economy, especially when this power is concentrated within a few firms.

Furthermore, the ongoing and increasing revolving door phenomenon clearly suggests excess coziness between industry and government, now to the extent that industry and government leaders of health care are becoming interchangeable.  This suggests that health care is increasingly run by this cozy ingroup, who very likely put their own interests ahead of those of patients and the public.

The continuing egregiousness of the revolving door in health care shows how health care leadership can play mutually beneficial games, regardless of the their effects on patients' and the public's health.  Once again, true health care reform would cut the ties between government and corporate leaders and their cronies that have lead to government of, for and by corporate executives rather than the people at large.

ADDENDUM (28 September, 2015) - This post has been republished on the Naked Capitalism blog,  and OpEdNews.

ADDENDUM (28 September, 2015) - See also more detail on Dr Califf's activities on the Portola board on the PEU Report blog. 

Pfizer's 13th Legal Settlement - Will it be Enough to End the Impunity?

It has been almost two months since we lasted noted misbehavior by giant global pharmaceutical firm Pfizer Inc. With little fanfare, however, a few small news items noted the corporation's latest legal settlements.

Deceptive Marketing of Protonix

The first settlement merited only a few paragraphs from Reuters.  The gist was:

Pfizer Inc will pay $55 million plus interest to settle charges that Wyeth promoted its acid reflux drug Protonix for unapproved uses and made unproven claims about the medicine, the U.S. Department of Justice said on Wednesday. 

The infractions took place between February 2000 and June 2001, long before the world's largest drugmaker acquired Wyeth in 2009 for $68 billion.

A report in the examiner explained that Wyeth did not merely go beyond the label in promoting Protonix, it went beyond the evidence.

Wyeth allegedly promoted Protonix as the 'best PPI for nighttime heartburn' even though there was never any clinical evidence that Protonix was more effective than any other PPI for nighttime heartburn. 

Furthermore, the charges were that systemic efforts to mislead were sanctioned by top management:

 The allegations in the complaint are that this superiority slogan was formulated at the highest levels of the company. Wyeth retained an outside market research firm, at the cost of tens of thousands of dollars, to ensure that sales representatives delivered that misleading superiority message.

Finally, the government asserted that Wyeth corrupted physicians' continuing medical education in the process:

Finally, the government alleges that Wyeth used continuing medical education (CME) programs to promote Protonix for unapproved uses. CME programs are sponsored by accredited independent providers, such as universities, nonprofit organizations, or specialty societies. Pharmaceutical companies are permitted to provide financial support for CME programs, but they are not permitted to use CME programs as promotional vehicles for off-label indications.

According to the complaint, Wyeth spent millions of dollars providing 'unrestricted educational grants' to CME providers, and these grants invariably included promises that Wyeth would not attempt to influence the content of the program in any way. Nevertheless, the government alleges that one of Wyeth’s core marketing tactics for Protonix was to use CME programs to drive off-label use of the drug. According to the complaint, the Protonix 'brand team' influenced virtually every aspect of these CME programs: program topics, speaker selection, organization, and content. In addition, the government alleges that Wyeth even insisted that the CME program materials use the same color and appearance as Protonix promotional materials–a tactic that Wyeth and the vendor called 'branducation.'

So it seemed that the company put on quite an effort to promote what we have called elsewhere pseudo-evidence based medicine, yet, like many other legal settlements involving large health care organizations, this one involved no penalties of any type against the people within the organization who authorized, directed, or implemented the bad behavior. 

 Misleading Marketing of Zyvox, Lyrica 

Another settlement, for a few dollars less, got even less attention.  Fox Business news did report this:

 Pfizer Inc. (PFE) agreed to pay a combined $42.9 million to North Carolina and 32 other states in a settlement of allegations that the drug maker used unfair and deceptive practices in the marketing of antibiotic Zyvox and nerve-pain medicine Lyrica.

I could find no detail about the sorts of deception allegedly involved in the news media.  What little more Fox provided did suggest that this case also involved pitching drugs in instances in which their use was unsupported by good evidence:

The states had alleged that Pfizer had marketed Zyvox as superior to another antibiotic in fighting certain types of infections, though there allegedly wasn't substantial evidence to support superior results for some uses that Pfizer claimed.

The states also alleged that Pfizer marketed Lyrica for some off-label, or unapproved, uses.

There was no hint that again any individual would suffer any negative consequences for this particular set of deceits either.

Avoiding Impunity as a Topic of Polite Discussion

We have discussed a seemingly endless parade of legal settlements by large health care organizations.  In almost none was there any consequence beyond a fine paid by the company, and sometimes a pledge that the company would thereafter behave better.  While these relatively small costs were diffused throughout the organizations, almost never did the people who authorized, directed, or implemented the bad behavior pay any price or suffer any penalty.  Thus we have opined again and again (e.g., most recently here) that these settlements have become just another cost of doing business, and have no power to deter future bad behavior.

In addition, we have noted not only have multiple organizations made such settlements, some organizations have settled again and again.  Yet even in the cases of these multiple organizational offenders, the individuals involved maintain their immunity from any negative consequences.  Thus these are examples of impunity.  

Transparency International declared 23 November, 2012, as the International Day to End Impunity, explained as follows:

At Transparency International we view impunity as getting away with bending the law, beating the system or escaping punishment. Impunity is anathema to the fight against corruption.

However, impunity is one of those concepts which never seems to be a subject of polite conversation in health care, or, as we say, it has become anechoic.  

Therefore, it is fascinating that while these two Pfizer settlements were announced almost simultaneously, each was discussed, such as it was, as if it occurred in a vacuum.  Moreover, it also seems that each settlement was crafted by law enforcers without any attention to the record of the company making the settlement.  Thus, any implications about impunity were avoided.

Pfizer's Multiple Ethical Opfenses

In fact, during the time we have been posting on Health Care Renewal, Pfizer has become one of the great repeat ethical offenders in the health care arena.  Its track record since the beginning of the 21st century, (with yello colored background below, compiled from this post), is remarkable.

In the beginning of the 21st century, according to the Philadelphia Inquirer, Pfizer made three major settlements,

October 2002: Pfizer and subsidiaries Warner-Lambert and Parke-Davis agreed to pay $49 million to settle allegations that the company fraudulently avoided paying fully rebates owed to the state and federal governments under the national Medicaid Rebate program for the cholesterol-lowering drug Lipitor.

May 2004: Pfizer agreed to pay $430 million to settle DOJ claims involving the off-label promotion of the epilepsy drug Neurontin by subsidiary Warner-Lambert. The promotions included flying doctors to lavish resorts and paying them hefty speakers' fees to tout the drug. The company said the activity took place years before it bought Warner-Lambert in 2000.

April 2007: Pfizer agreed to pay $34.7 million in fines to settle Department of Justice allegations that it improperly promoted the human growth hormone product Genotropin. The drugmaker's Pharmacia & Upjohn Co. subsidiary pleaded guilty to offering a kickback to a pharmacy-benefits manager to sell more of the drug.

Thereafter, Pfizer paid a $2.3 billion settlement in 2009 of civil and criminal allegations and a Pfizer subsidiary entered a guilty plea to charges it violated federal law regarding its marketing of Bextra (see post here).  Pfizer was involved in two other major cases from then to early 2010, including one in which a jury found the company guilty of violating the RICO (racketeer-influenced corrupt organization) statute (see post here).  The company was listed as one of the pharmaceutical "big four" companies in terms of defrauding the government (see post here).  Pfizer's Pharmacia subsidiary settled allegations that it inflated drugs costs paid by New York in early 2011 (see post here).   In March, 2011, a settlement was announced in a long-running class action case which involved allegations that another Pfizer subsidiary had exposed many people to asbestos (see this story in Bloomberg).  In October, 2011, Pfizer settled allegations that it illegally marketed bladder control drug Detrol (see this post). Finally, in August, 2012, Pfizer settled allegations that its subsidiaries bribed foreign (that is, with respect to the US) government officials, including government-employed doctors (see this post). 

By my count, the two current settlements would be numbers twelve and thirteen.  Of course, while I believe this list is accurate, it may be incomplete.

Since none of these posts involved any negative consequences for any individuals who authorized, directed, or implemented the bad behavior, or who profited from it, and none involved any changed in the leadership or organization of the company, this becomes an amazing record of the impunity of Pfizer leadership over time and space. 

Will Impunity Finally Lead to Outrage?

Impunity, though, is a concept that is beginning to command some attention.

The Brasilia Declaration which was published at the conclusion of the 15th International Anti-Corruption Conference (hosted by Transparency International) included:

it is clear we all face a common challenge in our work: impunity for those who abuse positions of power. 

If impunity is not stopped, we risk the dissolution of the very fabric of society and the rule of law, our trust in our politics and our hope for social justice.

Activists, businesspeople, politicians, public officials, journalists, academics, youth and citizens who gathered in Brasilia to discuss the threat of corruption made it clear that impunity undermines integrity everywhere.

Whether we are investing collective efforts and resources in fighting poverty, human rights violations, climate change or bailing out indebted economies, we need to give the people a reason to believe that impunity will be stopped.

While the two latest Pfizer settlements barely got media coverage, maybe a $1.9 billion dollar settlement in the US by international banking giant will get more attention.  The charges in this case were not merely deceiving some doctors and patients about drug efficacy and safety.  The company was accused of aiding money laundering by drug cartels, and facilitating rogue regimes get around international sanctions.  As the New York Times reported,

State and federal authorities decided against indicting HSBC in a money-laundering case over concerns that criminal charges could jeopardize one of the world’s largest banks and ultimately destabilize the global financial system.

Instead, HSBC announced on Tuesday that it had agreed to a record $1.92 billion settlement with authorities. The bank, which is based in Britain, faces accusations that it transferred billions of dollars for nations like Iran and enabled Mexican drug cartels to move money illegally through its American subsidiaries.

Unlike Pfizer's slow-motion impunity, this example got attention.  The Los Angeles Times noted,

The massive penalty still was not enough to appease some critics. No bank executives were charged as part of the investigation, leading some analysts to question the government's willingness to hold powerful Wall Street firms accountable.

'It's mind-boggling how they think you can have a financial system and allow this kind of impunity,' said William Black, a former banking regulator who aided federal prosecutors during the savings and loan crisis of the 1980s and 1990s. HSBC 'put the world at enormous risk.'

A NY Times editorial opened,

It is a dark day for the rule of law.   Federal and state authorities have not to indict HSBC, the London-based bank, on charges of vast and prolonged money laundering, for fear that criminal prosecution would topple the bank and, in the process, endanger the financial system.  They have also not charged any top HSBC banker in the case, though it boggles the mind that a bank could launder money as HSBC did without anyone in a position of authority making culpable decisions.

Clearly, the government has bought into the notion that too big to fail is too big to jail.  When prosecutors choose not to prosecute to the full extent of the law in a case as egregious as this, the law itself is diminished.  The deterrence that comes from the threat of criminal prosecution is weakened, if not lost.

So maybe this huge financial case will prove to be the straw that breaks impunity's back.  So I will close by quoting the end of the Brasilia Declaration, in the hope that a few people will take it to heart in the context of health care, as well as in finance.

To take this important struggle forward the international anti-corruption community should promote greater people engagement and find ways to provide greater security for anti-corruption activists.

Reducing impunity also requires independent and well-resourced judiciaries that are accountable to the people they serve.

We call on leaders everywhere to embrace not only transparency in public life but a culture of transparency leading to a participatory society in which leaders are accountable.

We call on the anti-corruption movement to support and protect the activists, whistleblowers and journalists who speak out against corruption, often at great risk.

It is up to all of us in government, business and society to embrace transparency so that it ensures full participation of all people, bringing us together to send a clear message: We are watching those who act with impunity and we will not let them get away with it.

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 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.

As was the case for nearly every other legal settlement we have discussed,

No individuals have been charged in any of these cases.

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 official "complaint" filed by the US Department of Justice 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 manipulation 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 here and here).  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 here. ) 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,

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."

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,

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.

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

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....

One really creative way to pay physicians to be exposed to marketing:

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.

Thus GSK simply paid physicians to use its drug, a practice characterized as kickbacks in the official complaint.  An article in the Guardian noted that the US Attorney involved in the case put it even more bluntly,

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.

Use of Key Opinion Leaders as Disguised Marketers

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.

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,

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,....

In particular,

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.

Also,

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.

Manipulation of Continuing Medical Education

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.

Furthermore,

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.

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 stealth marketing campaigns have come to light through legal action, and many other instances of manipulation and suppression of clinical research, use of KOLs as disguised marketers, kickbacks and bribes, and manipulation of CME 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 here).

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 here and here).

Although the current settlement will require a huge payment, as I have said many times before (as early as 2008, here), 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,

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.'

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 scooped me on the details of the settlement relevant to study 329.

ADDENDUM (11 July, 2012) - see also this post on the 1BoringOldMan blog.

Logical Fallacies in Defense of the European Society of Cardiology's Lenient Approach to Conflicts of Interest

The European Society of Cardiology just published its recommendations for interactions between medical societies and industry.(1)   The report emphasized the supposed benefits of industry relationships and funding, and suggested few restrictions on current practices.  Like other defenses of leniency towards conflicts of interest, its arguments seemed to rest on a series of logical fallacies.  

Wonderful "Innovations ... Through Productive Collaboration" - Appeal to Belief and the Fallacy of Division

The report made several arguments about the benefits of professional - industrial interaction.  These included:

In recent decades, cardiology has been a fast-moving medical speciality. Many advances have come from basic and clinical research conducted by universities and by pharmaceutical and medical device companies. Innovations have been realized in part through productive collaborations between clinicians, academia, and industry. Such links are essential and need to be encouraged and supported by appropriate investment if medical progress is to be sustained.

The notion that interactions between physicians and industry is a source, perhaps the most important source of wonderful "innovations" is often used to justify the sorts of interactions, involving payments by industry to academia and physicians, that are now prevalent. In this report, this first appears as an assertion without any evidence to justify it.

Later, the report noted:

The Association of American Medical Colleges has stated that there are benefits from effective partnerships between industry and academic medical centres.

This statement came with a citation, to a 2008 report entitled "Industry Funding of Medical Education."(2) This AAMC report, in turn, contained many similar assertions, e.g.,

An effective and principled partnership between academic medical centers and various health industries is critical in order to realize fully the benefits of biomedical research and ensure continued advances in the prevention, diagnosis, and treatment of disease.

However, the AAMC report also failed to cite any evidence in support of these assertions.

There are two major problems with these assertions, which form the foundations of both reports. The first is they do not seem to have a clear evidence base.

While the notion that current research efforts marked by substantial interaction between physicians, academia and industry are producing wonderful innovations is appealing, what evidence there is suggests that clinically important innovation is rare. For example, I quote a 2009 review of global drug discovery by Light(3) on whether new drugs represent advances over older treatments:

the best evidence of clinical quality comes from systematic efforts to assess therapeutic advantage and adverse effects compared with existing drugs. A detailed analysis of therapeutic quality in new drugs over the past twenty years found that 14 percent of all new chemical entities are either therapeutic breakthroughs or substantially superior to existing medications. Likewise, a comprehensive review of all new drugs approved between 1989 and 2000 in the United States concluded that 14.8 percent were new chemical entities that provided significant clinical improvement, and a Canadian review board concluded that 10.7 percent of new chemical entities in 2000–2004 did so.

Thus while many new drugs are introduced, only a few introduced recently were chemically unique or had effects different than older treatments.  I would argue that most of these will prove not to be truly clinically innovative, in that good clinical research will not show that they produce substantial improvements in clinical outcomes without major adverse effects for a good number of patients with not uncommon problems.  (It is not hard to think of really important innovations developed before the era of major industry-academic-physician interactions: antisepsis for surgery, anesthesia for surgery, antibiotics, hormone replacement therapy with insulin, thyroid hormone, etc, smallpox vaccination, polio vaccination, etc, etc)  However, it is actually very hard to think of more than a handful of new drugs or devices discovered in the last 20 years which were that hugely innovative.  (The closest might be multi anti-viral drugs used to treat HIV, and Gleevec for chronic myelogenous leukemia.)  If there has been very little really important innovation in the last 20 plus year era of enhanced industry-academic-physician interactions, these collaborations could not have produced tremendous innovation. 

So the report's arguments rests on an assertion that is not clearly justified, and which appears to be at best a huge exaggeration. Resting an argument on a belief that is not further supported by evidence amounts to a obvious logical fallacy.  It is an appeal to belief.

Furthermore, while both reports emphasize physician-industry collaboration or interaction, there are many ways interaction or collaboration can occur without involving substantial payments by the latter to the former. It is possible for two people or organizations to work together without one paying the other.  Yet both reports use the broad assertions about interaction and collaboration to justify interactions and collaborations in which industry makes substantial payments to physicians or academic institutions. This appears to be an example of the fallacy of division, that is, an unjustified assertion that "what is true of a whole must also be true of its constituents."

CME Would Wither if Financing Were Reduced, and Industry is the Only Possible Source of Such Money - A Slippery Slope and a False Dilemma

The ESC report made the argument that without industry funding, CME would wither. For example,

Should Europe choose to follow the strategy proposed in the USA, severing links between industry and medical societies, CME could be severely compromised. Relying completely on public funding is not a viable option for Europe at the moment. The removal of industry support for medical associations would be followed by increased fees and reduced attendance at congresses especially by clinical trainees and young fellows. It is the view of the ESC that in the absence of alternative funding, or until alternative funding is identified, maintaining links with industry is appropriate....

The argument is that CME would fail if financial support for it would be reduced, and that industry is the only possible source of financial support at the current level. The notion that CME must inevitably fail if financing of it were reduced is a slippery slope fallacy, that is, a statement that a inevitably causes b when such inevitability is not proven. Why could not adequate CME be done at a lower cost, even if the result were less luxurious? Furthermore, the notion that industry is the only source of funding is a false dilemma fallacy. In fact, there are other possibly sources of funding. Given that physicians are among the world's best paid professionals, why could they not pay for their own CME?

"Conflicts of Interest are Unavoidable and ... They Cannot Be Abolished" - False Dilemma

The third major argument on which the report bases its recommendations is encapsulated above, and was buttressed by:

The risk of bias in medical education is not restricted to activities that are supported by industry. It can affect any type of scientific communication, even an educational meeting organized independently by a university or medical association.

Underlying these assertions seem to be extremely broad definitions of bias and conflicts of interest, coupled with unwillingness to see a distinction between trivial and serious varieties of each. This again appears to be a false dilemma. The distinctions should be between no conflicts, trivial conflicts, and serious conflicts, not between no conflicts and any conflicts, even if trivial.  This also could be called an example of how "the perfect is the enemy of the good."  Even if perfectly preventing all conflicts of interest is impossible, does this imply that preventing serious conflicts of interest is not worthwhile.   

Summary

We have noted that logical fallacies are increasingly deployed to defend the status quo in health care, and particularly to defend the interests of those who are profiting the most from the current dysfunctional system.  We have noted that several defenses of the conflicts of interest generated by financial relationships between physicians and medical academics on one hand and commercial health care firms on the other, were based on logical fallacies.  (See examples here, here,  here, and here.)  I have yet to see a coherent, logical, fact-based argument that the benefits for patients' and the public's health of physicians and medical academics working part-time as consultants, advisers, speakers, and directors of health care corporations outweigh the obvious risks of biasing medical decision making, education and research in favor of vested interests.

So we add to our ongoing series how, based on a series of logical fallacies, the European Society of Cardiology provided a series of recommendations that allowed nearly any kind of relationship among CME speakers and selection committees and industry, as long as the relationships were disclosed.  The only relationships banned were those "which would represent a significant conflict of interest" for the Chairperson of a Congress Programme Committee.  Similarly, the only stipulations for the society's cardiology journals were that interests affecting editors and editorial board members must be declared, and board members and reviewers should decline reviews of manuscripts "relating to topics, drugs, or devices, in which they have significant commercial of academic interests."  The rules for guideline committees were somewhat more rigorous, but "receipt of consultancy fees or fees for lecturing would not debar an individual from being a member of a committee but must be fully disclosed."

It is discouraging that the web of conflicts of interest that currently enmeshes much of academic medicine and many medical professionals is so heavily defended.  It is more discouraging that its defenders include so many prominent academics and practicing physicians.  It is more discouraging that so many well trained people resort to logical fallacies to make their arguments, and do so in prestigious scholarly journals.

Our continuing series about how logical fallacies are used to support the status quo and the powers that be in health care suggests, if nothing else, that health care professional education ought to include courses in logic.

Finally,  in 2011, I noted, "I have also yet to see an argument in favor of conflicts of interest made by anyone who does not have such conflicts."At least, however, up to that point I had not noted any such arguments made by people who had much power to enforce their views, as opposed to the ability to just express them.  Last month, however, I discussed how the leader of one of the most acclaimed US medical schools made an argument in support of conflicts of interest based on logical fallacies,  Now we have just seen such arguments made by the leaders of European cardiology.  The new paper suggested that disclosure is the best way to manage conflicts of interest.  True to this belief, the paper included a disclosure section that took up an entire journal page.

It seems likely that number and magnitude of ongoing commercial interests so disclosed may have influenced the content of the position paper.  Yet while it may be unsurprising, it is most disappointing that conflicts of interest are now being uncritically and illogically publicly defended by people in positions to exert so much influence on health care.

The noted cognitive psychologists George Loewenstein, Sunita Sah, and Daylian Cain just asserted in JAMA(4):

Conflicts of interest, including fee-for-service arrangements, are at the heart of the astronomical increases in health care costs in the United States, and transparency is not substitute for more substantive reform.

True health care reform requires such substantive reform of the financial arrangements among corporations that sell health care services or products and health care professionals, others who make decisions about patients' or the public's health, and academic health care institutions. To decide how to accomplish such reform, we need a better discussion informed by logic and evidence, sans logical fallacies. Those who lead health care ought to be able to participate in this discussion under these conditions.

References
1. ESC Board. Relations between professional medical associations and the health-care industry, concerning scientific communication and continuing medical education. Eur Heart J 2012; 33: 666-674. Link here.
2. Association of Americian Medical Colleges. Industry Funding of Medical Education. Washington, DC: AAMC, 2008. Link here.
3. Light DW. Global drug discovery: Europe is ahead. Health Aff 2009; 28: w969-w977. Link here.
4. Loewenstein G, Sah S, Cain DM. The unintended consequences of conflict of interest disclosure. JAMA 2012; 307: 669-670. Link here.

MISSING in ACTION on MEDSCAPE

MISSING in ACTION on MEDSCAPE

Charles Nemeroff has been in the news lately, under investigation by Senator Grassley for allegedly violating NIH regulations on conflict of interest and disclosure. The fallout to date includes his severance from several NIH-funded projects at Emory University School of Medicine, a freeze of NIH funding for a major center grant, and his stepping down from Emory’s chair of psychiatry while an internal investigation proceeds. Some amazing documents were released by the Senator. Among other surprises, they contained a scathing critique of a Nemeroff publication by Emory’s Dean Claudia Adkison, and evidence that Dr. Nemeroff tried to get himself off the hook within Emory by smearing third parties and blaming them for harassment. Now that these internal documents have been released by the Senate Committee on Finance and then appeared in The New York Times, Dr. Nemeroff will have even more explaining to do.

The word is finally out. Dr. Nemeroff’s credibility is under a cloud, to say the least, and his influence is rapidly waning. After all, who wants to be associated with a suspect and a loser? In the hardnosed, commercial world of Continuing Medical Education, for instance, the signs are that Dr. Nemeroff is toast. Whereas he once coordinated multi-city traveling CME road shows and a parade of spots on CME websites like Medscape, his profile now is suffering. Go to this Medscape website, for instance. You will find that his current Expert Viewpoint spots are missing, replaced by the message, “This article is temporarily unavailable.”

Well, good for Medscape. They came in for their share of criticism, here and here, a while back. Now they deserve credit for displaying ethical standards. Meanwhile, we are waiting for another company called CME Outfitters to get the message. Dr. Nemeroff is slated to moderate a raft of new programs for this company in the coming weeks, sponsored by corporations like Pfizer, AstraZeneca, and Ortho-McNeil Janssen. CME Outfitters' logo, after all, is Education with Integrity. Sooner or later the pharmaceutical corporations, like the CME companies, will understand that they are not helping themselves by trotting out a shopworn and sleazy KOL figurehead like Nemeroff for their marketing efforts. And other KOLs who up to now were willing to "wet their beaks" in these CME forums controlled by the Boss of Bosses Nemeroff will now be leery of associating with him.

The fallout continues.

Bernard Carroll

MEDSCAPE'S CME ETHICS

17 June 2008

MEDSCAPE’S CME ETHICS

Like global warming, the erosion of professional values and medical education by commerce shows no sign of slowing. The latest scandals involve Medscape. Medscape is a medical communications company that produces and distributes CME programs and other quasi-educational offerings, such as “Expert Interviews” and News items. A subsidiary of WebMD, Medscape is accredited by ACCME, and it relies on drug company money for its production costs. Medscape also displays multiple advertisements on every web page. Medscape uses salaried and contract medical writers to produce the “educational material.” The content is pedestrian, mainly because it makes no pretense of really educating – it is primarily a vehicle for promoting the sponsors’ products with varying degrees of slyness and subtlety, as Daniel Carlat has documented here http://carlatpsychiatry.blogspot.com/2008/06/medscapes-cme-corruption.html#links Some items are academic wallpaper, non-promotional pieces designed to create an appearance of commitment to education. For most featured items, Key Opinion Leaders (KOLs) are hired to push the material. These KOLs are paid for their roles, although Medscape never says so, much less discloses how much it pays. If they wish to be engaged regularly, the KOLs know they need to stay “on message.” These are standard arrangements in today’s amoral world of CME. Daniel Carlat recently published a fine exposé of Medscape’s corruption of CME standards (link above).

An especially distasteful practice is Medscape’s use of the names, reputations, and credibility of major professional societies to give its indifferent CME offerings and infomercials more pizzaz. Just to give two examples, Medscape web pages are currently hijacking the public images of both the American Psychiatric Association (APA) and the American College of Neuropsychopharmacology (ACNP), featuring highlights of these organizations’ annual meetings as CME and other items. These “highlights” from the APA and ACNP meetings are offered by Medscape FOR CME CREDIT!!! For us to call this presumptuous would be an understatement. For Medscape to dress it up with sanctimonious statements about avoiding conflict of interest is insufferable.

Both APA and ACNP annual meetings are closed events, so how does a commercial CME outfit like Medscape get its hands on these restricted materials? The most likely explanation is that venal KOLs accept Medscape payments for producing puff pieces with the organizational tagline (highlights of the APA/ACNP meeting!). In effect, these KOLs trade on their membership in professional organizations for personal gain in return for “authoring” Medscape-produced CME items, “Expert Interviews” and News pieces. How tacky is that? The KOLs who “authored” mini-manuscripts or provided “Expert Interviews” for Medscape’s “highlights” of the 2007 ACNP annual meeting, whether as infomercials or wallpaper, should know better. You can find them here and in the associated links: http://www.medscape.com/viewprogram/8683

Medscape is paid by Pharma to produce these items. The APA 2008 annual meeting highlights on Medscape’s website were supported by an “independent educational grant” from Shire and by an “unrestricted educational grant” from Bristol-Myers Squibb Company/Otsuka America Pharmaceuticals, Inc. It is a good bet that Medscape shares none of that revenue with the APA. Likewise, the ACNP 2007 annual meeting “highlights” were supported by an “independent educational grant” from Vanda Pharmaceuticals. We can be sure ACNP saw none of that revenue.

So what we have is Medscape profiting from Pharma sponsors while juicing up their mediocre CME offerings with tag lines to “highlights” of the APA and ACNP annual meetings. How tacky can you get? How tacky? This tacky: Here is the disclaimer published by Medscape’s lawyers regarding the ACNP meeting.

Legal Disclaimer
The materials presented here do not reflect the views of Medscape or the companies providing unrestricted educational grants. These materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. All readers or continuing education participants should verify all information and data before treating patients or employing any therapies described in this educational activity.
The materials presented here were prepared by independent authors under the editorial supervision of Medscape and do not represent a publication of the American College of Neuropsychopharmacology. These materials and the related activity are not sanctioned by the American College of Neuropsychopharmacology or the commercial supporter of the conference and do not constitute an official part of that conference.
Copyright © 2008 Medscape.


An additional disclaimer states, “This activity is not sanctioned by, nor a part of, the American College of Neuropsychopharmacology.” Well, fine. If it wasn’t sanctioned, why is Medscape splashing it over its web pages? I am confident ACNP gave Medscape no such authorization.

One hopes that APA and ACNP will publicly disown this corrupt use of their names and reputations for commerce by Medscape. The situation with APA is problematic because the incoming APA president, Alan Schatzberg, has been a frequent “Expert Interviewee” on Medscape. It remains to be seen whether his compromise and conflict will affect the organization’s response.

So, nobody at Medscape is accountable for the bias and bs in these items, even though they were written by Medscape staff and contractors. Medscape’s disclaimer tells us to go after the “independent authors.” That’s exactly what I intend to do in my next posting. Meanwhile, if Medscape wants credibility it will need to clean up its act. A good place to start would be to stop using these compromised KOLs who push infomercials and who provide soothing wallpaper. The real solution would be for Medscape to stop its skimming and money laundering activities altogether. Perhaps that is hoping for too much. Or they could just run naked advertising and they won’t need to bother with ACCME requirements. On the other hand, self-respecting health care professionals can just say no to Medscape’s kind of crap.

And what exactly does an “independent educational grant” mean, anyway? We will examine that trope in my next posting, which features the poster boy for compromised KOLs in psychiatry, Charles Nemeroff, MD from Emory University’s department of psychiatry. In that example, Medscape joins forces with Nemeroff to promote an entirely new level of sleaze. Stay tuned.