Merck Settles Another Vioxx Case

All the shenanigans that went on in the course of Merck's marketing of the now withdrawn Cox-2 inhibitor non-steroidal anti-inflammatory drug Vioxx have provided grist for the Health Care Renewal mill since 2005.  For example, see these posts:

- here about ghost-writing of a Vioxx research publication;
- here, and here about allegations that Merck executives tried to intimidate Vioxx critics;
- here about how advocates of an extreme laissez faire approach to regulation of health care corporations used illogical arguments about the Vioxx case;
- here about how an apparently major clinical trial of Vioxx turned out to be a "seeding trial," that is, a study really meant to recruit supposed physician-researchers as prescribers; and
- here about how one once prominent Vioxx researcher pleaded guilty to fraud in connection with his research on other drugs. 

Thus, the Vioxx case provides a good lesson about some of the tactics used to deceptively and unethically promote health care products (pharmaceuticals in this case).

Merck just announced just the latest settlement of Vioxx related legal actions, as reported by Business Week:

Merck & Co. agreed to settle shareholder lawsuits over the withdrawn Vioxx painkiller by strengthening its drug-safety procedures, appointing a new chief medical officer and paying $12.2 million in legal fees.

Merck would appoint one committee to address risks that require immediate action and another to monitor the safety of drugs, the company said in a regulatory filing. Merck would also amend its code of conduct to promote scientific and academic integrity as well 'honest communication' with doctors.

'In all research endeavors that are sponsored by Merck, we will refrain from attempting to influence inappropriately the results and conclusions of such research,' according to the amended code. 'We strive for all communications with the medical community to be accurate, truthful and consistent with labeling.'

Also,

The company will be required to make corporate governance changes and “supplement existing policies and procedures,” ... [a Merck spokesperson] said.

Merck would submit results of clinical trials to a public registry, with its compliance overseen by an independent third party.

The chief medical officer will have an 'executive voice' on product safety issues independent of Merck Research Laboratories.

Note that this settlement is only of one type of lawsuit, as described in a Wall Street Journal article,

The pact, which is pending final court approval, would resolve state and federal shareholder 'derivative' complaints (which are brought by shareholders on behalf of a company) alleging that current and former Merck officers and directors breached their fiduciary duties in handling Vioxx.

Merck had already settled thousands of lawsuits,

Since the Vioxx controversy erupted, about 27,000 personal-injury lawsuits have been filed, the company says. Merck has been challenging all of the cases and settled many of them. Most notably, it agreed to a pay $4.85 billion to settle personal-injury claims of more than 40,000 people. In another settlement, the company will pay $80 million to resolve 190 claims filed by drug-benefit plans seeking to recover costs of paying for Vioxx use.

Merck has lots of other legal actions to go through,

The Vioxx litigation remains far from over. The U.S. Supreme Court is weighing a separate shareholder case, seeking billions of dollars in damages from the company. Merck disclosed last year the U.S. Attorney's office in Boston was conducting a grand-jury investigation of Merck's handling of Vioxx. The claims of some 310 plaintiff groups are outstanding in courts in the U.S., according to the securities filing. There are also cases overseas, including Australia and Turkey.

So the parade of legal actions and settlements thereof continues.  We believe that the scope of this parade provides some sort of index of bad behavior by the health care organizations needing to make such settlements.  Most of these legal results are reported on in the business media, and rarely appear in any medical, health care research, or health policy journals.  I submit that were health care professionals, health care researchers, and health policy makers more systematically aware of these cases, they might realize that unethical and sometimes illegal behavior, often generated by bad leadership unrestrained by poor organizational governance, is a major cause of the current, seemingly intractable health care crisis.

One notable attribute of the current Vioxx settlement is that it does mandate some changes in Merck's governance and leadership meant to prevent future cases similar to this one.  These include developing leadership structures and changing the company's code of conduct to emphasize the need for "truthful" communication, and the need to refrain from "inappropriately" influencing research. 

On Health Care Renewal we have discussed numerous examples of deceptive practices by health care organizations, often affecting marketing, and of manipulation and suppression of research.  It is a small step forward for one company to commit to honest communications and to not manipulate research.  A better code of conduct may at least be a start towards an organizational ethics policy, which in turn may have the potential to actually improve behavior. 

On the other hand, typical settlements that involve only monetary damages paid by the organization seem to have little deterrent effect on future bad behavior. Usually, the companies involved only need to pay fines, and no individual who performed, directed or approved unethical or illegal acts suffers any negative consequences. I submit once again that such fines are viewed merely as costs of doing business by the affected companies, and do not deter future bad behavior. Until the people who approve, direct, and perform unethical or illegal acts pay some penalties, expect such acts to continue, at best deterred only slightly by written policies that condemn them. I again suggest that to truly reform health care, we need rigorous regulation of health care organizations that has the power to deter unethical behavior that may risk patients' health

Post Title → Merck Settles Another Vioxx Case

Physician Pleads Guilty to Fraud for Fabricating Celebrex (and Other) Study Data

As reported by the Springfield, MA, Republican:

A former chief of acute pain at Baystate Medical Center has agreed to plead guilty to falsifying medical research and must pay $420,000 in restitution to pharmaceutical companies, federal court records show.

Dr. Scott S. Reuben, of Longmeadow, was charged on Thursday with health care fraud. He signed a plea agreement with prosecutors a week earlier.

Reuben prompted a furor in the medical community in March, when he was accused of making up research results in at least 21 published studies and inventing patients in certain instances.

In one notable instance,

In 2005, Reuben received a $74,000 research grant from pharmaceutical giant Pfizer, agreeing to test Celebrex as a component of the multimodal therapy. He claimed to have treated 200 patients, 100 with Pfizer's product and 100 with a placebo.

'In fact, Reuben had not enrolled any patients into that study and the results reported both to Pfizer and to the Anesthesia and Analgesia Journal and in turn to the public were wholly made up by Reuben,' the charge states.

Albert said the fabrications were discovered by medical staff within the hospital during a routine review at the hospital's 'research week,' when clinicians design poster displays of their studies.

A report in the New London, CT, Day indicated the scope of Reuben's fake research:

Anesthesia & Analgesia later had to retract 10 papers authored by Reuben, and medical experts at the time said at least 21 journal articles by the anesthesiologist appeared to have been fabricated.

The agreement calls for Reuben to pay restitution of $296,557 to Pfizer and $16,000 to Wyeth Pharmaceuticals, two companies that merged last fall. Merck & Co. would receive $49,375 from the agreement, according to documents.

In addition to his fabricated Celebrex studies, Reuben had pretended to do research that backed the effectiveness of other pain drugs, including Pfizer's Bextra and Merck's Vioxx, according to prosecutors. Bextra and Vioxx later were pulled from the market because studies showed they increased the risk of death from heart attacks and strokes.

In addition, Reuben published data showing that Pfizer's antidepressant Effexor had exhibited painkilling properties.

Reuben's studies had been considered pioneering at the time they were published. His data had supported the use of two of Pfizer's major products - Celebrex and Lyrica - in combination to treat certain types of post-operative pain.

Reuben 'was a regular on the medical lecturing circuit,' according to court documents, and 'had become a well known figure in the anesthesia and pain management medical communities.'

Pfizer said previously that it had supported five of Reuben's research initiatives. Pfizer, which declined at the time to reveal how much it paid Reuben over the years to be part of its speakers' bureau, said the company played no part in the fraud.

Asked for a comment Friday, Pfizer was not able to provide a timely response.

Note that we usually do not post about stories of individual's clinical research misconduct, not because it is unimportant, but because individual misconduct may be related more to an individual's motives and character than to concentration and abuse of power in health care.

However, in this case it appears that Dr Reubens was enabled, at least in the psychological and logistical senses, by pharmaceutical companies happy to sponsor research which suggested the effectiveness of their products.  Since Dr Reubens apparently fabricated most of his data, notice that he apparently deliberately fabricated data that made Pfizer's Celebrex, Bextra, Lyrica, and Effexor, and Merck's Vioxx look good.  Perhaps there was careerism here.  Positive studies about "innovative" effective drugs are more likely to get published than negative studies or studies of old drugs.  However, we have noted before that pharmaceutical (and biotechnology and device) companies like to sponsor studies with results that make their products look good. 

One bit of good news in this story is that Reuben's colleagues at the hospital apparently were able to uncover the fabrications when they had an opportunity to critically look at data from several of his studies.

Certainly some Pfizer employees had easy access to the same data.  But perhaps they would not have thought to look at it critically as long as it was so unrelentingly positive about their company's products. 

As we have said before, health care professionals, policy makers and patients ought to be extremely skeptical of clinical studies sponsored (and often deeply influenced) by those with vested interests in the studies' turning out in certain ways.  We ought to reconsider national research policies that have turned over sponsorship of the majority of clinical research to those with such vested interests.

Hat tip to Prof Margaret Soltan on the University Diaries blog.

ADDENDUM (19 January, 2010) - see also comments on the Alison Bass Blog.

Post Title → Physician Pleads Guilty to Fraud for Fabricating Celebrex (and Other) Study Data

Does the CEO of Google Use Google? - And: Platform, Platform, Who's Got The Platform?

Over at the WSJ health blog, reporter Jacob Goldstein's Jan. 8, 2010 post "Google CEO & Harvard Surgeon Talk Health IT" quotes Google's CEO:

"Google’s CEO Eric Schmidt doesn’t know why docs haven’t embraced databases to help them sort through medical information."

[Schmidt said] ... So when you show up at the doctor with some set of symptoms, in my ideal world what would happen is that the doctor would type in the symptoms he or she also observes, and it would be matched against the data in this repository

[such as DXplain? -- which we learn from a - er, um, Google search - was developed starting in the mid 1980's by medical informatics researchers who actually know this domain, and which offers this explanation and warning: "DXplain uses an interactive format to collect clinical information and makes use of a modified form of Bayesian logic to derive clinical interpretations ... DXplain does not offer definitive medical consultation and should not be used as a substitute for physician diagnostic decision making"? - ed.]

... Then this knowledge engine would use best practices, and all the knowledge in the world to give physicians some sort of standardized guidance. This is a generalized form of the checklists that you’re talking about …

As computer scientists, this is a platform database problem, and we do these very, very well, as a general rule. And it befuddles me why medicine hasn’t organized itself around these platform opportunities. [No - the successful practice of medicine is not a 'platform database' or any other reductionistic information retrieval problem - ed.]

I note that IT personnel like to refer to "platforms", "solutions" - a rather presumptuous term, "paradigms", and other buzzwords to mask the fact that what they're referring to are more commonly known as "hardware" and "software" and arrangements thereof.

Does this "platform opportunity" view reflect naïveté about the complexities of medicine and medical decision making, or does it reflect something else? Could this "befuddlement" be construed as calling physicians obtuse? Is this yet another example of what I referred to in my post "Healthcare IT Failure and The Arrogance of the IT Industry" and other writings as a cross-occupational invasion of medicine by IT?

IT personnel seem to have a propensity to offer healthcare-related opinions far outside their own areas of expertise -- or if in healthcare organizations, edicts - based upon the narrow view of their own relatively linear and deterministic fields. The risk is, especially when coming from high perches, that such opinions and edicts can result in deleterious actions (e.g., government initiatives).

In an absurdist reductio ad absurdum, deliberately made absurdist due to many years of exposure to equally absurd (to those with actual domain experience) "who needs medical school/residency/patient care experience to profess on medical matters?" attitudes:

Why don't physicians offer the advice that Google could improve its search algorithms, or Intel and AMD their microprocessors, by utilizing intelligent psittacine platforms as in this British Broadcasting Company (BBC) video narrated by a true technology expert, Captain James T. Kirk?

Kirk did have a (computerized) physician son: Nomad!

----------------

Quite seriously, physician reluctance to "embracing databases" and health IT in general is not about database platforms. I only wish it were so simple.

The WSJ seems to understand this. In a Jan. 12, 2009 article by reporter Bret Stephens entitled "Can Intelligence be Intelligent?", the observation is made that technology is a mere facilitator, and intelligent, well trained, experienced, critical-thinking people are the enablers of any complex field that requires human judgment. They must be unfettered by machine and bureaucrat:

... Terrifying as the thought may be to many of its current practitioners, the true art of intelligence requires, well, intelligence. That is a function neither of technology nor of "systems" [a.k.a. "platforms" - ed.], which begin as efforts to supplement and enhance the work of intelligence and typically wind up as substitutes for it. It is, instead, a matter of experience, intellect, initiative and judgment, nurtured within institutions that welcome gadflies in their midst.

I've left the following comment at the WSJ health blog:

Mr Schmidt,

If you’d like to learn more about why many physicians are reluctant to embrace clinical IT, you might also do a Google search on “healthcare IT failure” and similar terms.

Need I say anything more about the irony of that advice?

I'd also noted a fixation on "platforms" as solutions to biomedical problems (best when they come in shrinkwrapped, off the shelf, "on the IT roadmap" packages!) in my June 2008 post "An Open Letter to Merck CEO Richard Clark on Merck's Mission to Rediscover the Wheel."

A nonmedical research IT leader, who'd found a move from basic research to clinical IT "quite an eye opening experience" (i.e., a domain in which she had little or no experience but was paradoxically appointed to lead) talked all about "platforms" in Bio-IT World:

... We've invested a lot in some core platforms; we need to start translating that into results in the clinic at some point. And so having people who have an understanding of what does that really take to help inform the earlier research directions, the platform directions [i.e., research direction = platform direction - ed.], is a key theme...We already have siloed platforms to show that data, we need to integrate it more than it is... combining the results data from clinical samples with the associated patient data, what's that platform?

Platform, platform, platform. Who's got the platform?

My comments to that CEO in my Open Letter were that this was the wrong mindset and question, based upon an IT person's focus on information technology. This is as opposed to a focus on information science and on facilitating people in interacting with data and information in order to gain actionable knowledge, i.e., an information science and human-computer interaction-based approach that those in medical informatics thought about long ago.

In line with the conclusions of Greenhalgh et al. [1] who called for "eschewing sanitized accounts of successful projects" and instead recommending studies of clinical IT in organizations that “tell it like it is” using the de-identified critical fiction technique, I'd written on how conflation of information technology and information science impaired R&D in pharma at my essay "Sure path to R&D failure: Conflation of IT with information science in the pharmaceutical industry."

That piece and the aforementioned Open Letter were written before Merck sold itself to Schering-Plough in a "reverse merger" due to the unsustainability of doing business from an empty wagon of new products, a sign of just how well this IT-centric "platformania" has been working out for R&D.

In the information science-centered view and approach, the "platform," a.k.a. computer technology, is merely a canvas and facilitator, the artist (clinician or scientist) and the brush wielded by them being the primary enabler of and contributor to the masterpiece.

Unfortunately, I don't think anyone is "home" in pharma or in the HIT sector anymore to parse these ideas; in fact I've only recently learned that the people I did work with who could parse these ideas into creative reality were laid off by the very IT people making such statements and asking such questions.

IT personnel perhaps need to move away from their reductionist platformania. (Perhaps they are confusing "platforms" with "pixie dust.") Rather, they need to start thinking in terms of facilitating clinicians and scientists through domain specific and individualized-to-need information science and HCI innovation that arises of true cross-disciplinary expertise.

They need to leave creation of cybernetic miracles to people such as Irwin Allen and George Lucas. And platforms to carpenters.

-- SS

[1] Tensions and Paradoxes in Electronic Patient Record Research: A Systematic Literature Review Using the Meta-narrative Method. Greenhalgh, Potts, Wong, Bark, Swinglehurst, University College London. Milbank Quarterly, Dec. 2009. Available at: http://eprints.ucl.ac.uk/18821/

Post Title → Does the CEO of Google Use Google? - And: Platform, Platform, Who's Got The Platform?

The Door Revolves: Tufts Medical School Dean Goes Back to Merck

A little news item in the Newark Star-Ledger:

Merck announced the appointment of Michael Rosenblatt as executive vice president and chief medical officer.

The appointment, which was announced this morning by the company, is effective immediately.

Rosenblatt will be responsible for bringing greater focus to Merck’s global medical activities as well as shaping innovative medical strategies. He will report directly to CEO Richard Clark.

Rosenblatt has served as dean of Tufts University Medical School since 2003.

Earlier, he was senior vice president for research at Merck Sharp & Dohme Research Laboratories, where he co-led the worldwide development team for Fosamax, Merck’s treatment for osteoporosis.

A quick Google tour revealed that while he was Dean, Dr Rosenblatt also served as a Scientific Advisor to Boston Millenia Partners, a venture capital firm; a Founder and then Scientific Advisor to Nuvios, which now is known as Radius Pharmaceuticals;  an Advisor to Puretech Ventures, which specializes"in company creation and early-stage investment in novel therapeutics, medical devices, diagnostics, and research technologies"; and a Director of Shire, "one of the world’s leading specialty biopharmaceutical companies."

This is a reminder how fuzzy the line has become between medical academics and health care corporations.  Here is an example of someone who alternated his main employment between leadership posts in academic medicine and in the pharmaceutical industry, but while in academia maintained a string of part time commitments to a further variety of biotechnology and pharmaceutical companies, and related venture capital firms.  Given all these positions and financial relationships, who knows where his main allegiance was? 

I would hope that the Dean of  a medical school would be the primary steward of the academic and clinical missions.  But what kind of stewardship can one expect from someone who came from one lucrative position in the pharmaceutical industry, and was to go back to an even higher level position, and who worked for several biotechnology/ pharmaceutical firms, and venture capital firms on the side?

Hat-tip to Shearlings Got Plowed blog.

Post Title → The Door Revolves: Tufts Medical School Dean Goes Back to Merck

Medical Informatics, Pharma, Health IT, and Golden Advice That Sits Sadly Unused

In recent correspondences with colleagues I was reminded of a letter I wrote seven years ago that was published in Bio-IT World, a journal about biomedicine focusing mainly on pharma, bioinformatics and related fields.

As the sole formally-trained Medical Informatics specialist at Merck, I wrote:

Medical Informatics MIA [Missing in Action - ed.]
Bio-IT World
August 13, 2002

Dear Bio-IT World:

I enjoyed reading the article "Informatics Moves to the Head of the Class" (June Bio·IT World). Thank you for spotlighting the National Library of Medicine (NLM) training programs in medical informatics and bioinformatics, of which I am a graduate (Yale, 1994).

Bioinformatics appears to receive more media attention and offer more status, career opportunities, and compensation than the less-prestigious medical informatics.

This disparity, however, may impede the development of next-generation medicines. Bioinformatics discoveries may be more likely to result in new medicines, for example via pharmacogenomics, when they are coupled with large-scale, concurrent, ongoing clinical data collection. At the same time, applied medical informatics, as a distinct specialty, is essential to the success of extensive clinical data collection efforts, especially at the point of care.

Hospital and provider MIS personnel are best equipped for implementing business-oriented IT, not clinical IT. Implementing clinical IT in patient-care settings constitutes one of the core competencies of applied medical informaticists.

Informatics specialists with a bioinformatics focus — even those coming from the new joint programs — usually are not proficient in hospital business and management issues that impede adoption of clinical IT in patient care settings. Such organizational and territorial issues are in no small way responsible for the low utilization of clinical IT in patient care settings.

It will be important for medical informaticists focused in the clinical domain and bioinformaticists specializing in the molecular domain to collaborate with other specialists in order to best integrate clinical and genomic data.

Further information on these issues can be found in the book Organizational Aspects of Health Informatics: Managing Technological Change, by Nancy M. Lorenzi and Robert T. Riley (Springer-Verlag, 1995). Various publications from the medical informatics community, such as the American Medical Informatics Association (www.amia.org) and the International Medical Informatics Association (www.imia.org), are also useful.

Scot Silverstein, MD
Director, Published Information Resources & The Merck Index
Merck Research Laboratories

I was also responsible for the entry of the term "Medical Informatics" into the controlled vocabulary pool used for various purposes at Merck.

As far as I can tell, the Medical Informatics talent gap still exists in all major pharmas despite writings on the topic from colleagues as well as myself. With the present turmoil including declining pipelines, mergers and mass layoffs pending in many large pharmas, and even despite Medical Informatics on a fast path to being declared a full medical subspecialty, it is likely this gap will persist for years longer. This is a shame. The field offers insights that can help R&D substantially, and I speak from direct experience from my time in that domain.

I am reminded via all this of another industry that seems to hurt itself via ignoring the advice of Medical Informatics professionals, the health IT industry. Healthcare IT is actually the core competence of Medical Informatics professionals, but those people are under-represented in the higher ranks of the health IT industry as well. Many job postings seek such people, but for lower level roles (as I've posted here in the past), and/or conflate formal training with informal experience and with those who qualify for the title of Medical Informaticist like I qualify (being an amateur radio licensee, extra class) as a professional RF engineer.

The irony is this: the wisdom of the Medical Informatics field on health IT goes back not years, but decades. It is advice that could have made the vendors much higher margins, allowed them to produce better products, avoid the government regulation that is now nearly inevitable (in some EU countries, clinical IT has already been determined to be a medical device requiring regulation), and in many cases, enabled corporate longevity.

Yet the teachings and accumulated wisdom of the field were, and largely still are, ignored, making books such as the new "H.I.T. or Miss: Lessons Learned from Health Information Technology Implementations" necessary even in 2009.

Here is just a small sampling of that wisdom:

Dr. Donald A. B. Lindberg (now Director of the U.S. National Library of Medicine at NIH), 1969:
"Computer engineering experts per se have virtually no idea of the real problems of medical or even hospital practice, and furthermore have consistently underestimated the complexity of the problems…in no cases can [building appropriate clinical information systems] be done, simply because they have not been defined with the physician as the continuing major contributor and user of the information."


Dr. Octo Barnett's [Harvard] health IT Ten Commandments, 1970:
1. Thou shall know what you want to do
2. Thou shall construct modular systems - given chaotic nature of hospitals
3. Thou shall build a computer system that can evolve in a graceful fashion
4. Thou shall build a system that allows easy and rapid programming development and modification
5. Thou shall build a system that has consistently rapid response time and is easy for the non-computernik to use
6. Thou shall have duplicate hardware systems
7. Thou shall build and implement your system in a joint effort with real users in a real situation with real problems
8. Thou shall be concerned with realities of the cost and projected benefit of the computer system
9. Innovation in computer technology is not enough; there must be a commitment to the potentials of radical change in other aspects of healthcare delivery, particularly those having to do with organization and manpower utilization
10. Be optimistic about the future, supportive of good work that is being done, passionate in your commitment, but always guided by a fundamental skepticism.

[Dr. Barnett played a key role in the 2009 National Research Council report about current approaches to health IT being inadequate, Press Release at http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12572, and full report "COMPUTATIONAL TECHNOLOGY FOR EFFECTIVE HEALTH CARE: IMMEDIATE STEPS AND STRATEGIC DIRECTIONS. - ed.]


Dr. Morris Collen's Five Rules, 1972
Most common causes of health IT failure:

• Suboptimal mix of medical and computer specialists … resulting in communications difficulties and in the computer staff underestimating the vast medical needs
• Gross underestimation of the large amounts of money needed
• Suboptimal systems approach with serious incompatibilities between modules
• Unacceptable terminals
• Inadequate management organization and poor judgment
  

Dr. R. Friedman, Reasons for slow spread of EMR, 1977:

• Poor engineering and unreliability
• Physicians not provided with computer-based applications that exceeded their own capability!
• Inability to prove a positive effect on patient care
• Difficulty transferring one application from one institution to another
  

(All taken from Collen's "A history of Medical Informatics in the United States, 1950-1990".)

I might add that the PC did not even exist in 1977, unless you consider the Altair and Heathkit H8 "personal computers."

Four-decades-old wisdom like this, and much more, sits out there in the ether and in the Medical Informatics field's professionals like a pot of gold, but is apparently considered as valuable as lead by the HIT - and pharma - industries. I find this amazing - and a pity.

-- SS

Post Title → Medical Informatics, Pharma, Health IT, and Golden Advice That Sits Sadly Unused

Again, Defending Conflicts of Interest with Logical Fallacies

The latest version of the argument that we are all getting too worked up over conflicts of interest in health care has appeared, this time in a scholarly, peer-reviewed journal. (Hirsch LJ. Conflicts of interest, authorship, and disclosures in industry-related scientific publishing: the tort bar and editorial oversight in medical journals. Mayo Clinic Proc 2009; 84: 811-821. Link here.) The major point of the paper seems to be that payments to physicians, particularly academic physicians by pharmaceutical, biotechnology, and device companies are necessary for medical progress, so instead of perseverating about them, we all should pay far more attention to the evil of payments made for expert testimony by physicians who serve as expert witnesses in litigation against such companies.

In the Hooked: Ethics, Medicine and Pharma blog, Dr Howard Brody addressed this main argument, while dismissing the bulk of the article as merely "illogic and innuendo." I think that Dr Brody failed to grasp the educational opportunities that the Hirsch article presented. It offers a true cornucopia of logical fallacies, making it ideal teaching material for the sort of course in logic and evidence that should be taught in all our medical schools, but is not.

So let me use this "teachable moment" to address just some of the many logical fallacies that Dr Hirsch so enthusiastically employed, in order of their first appearance in his article.

Appeal to Ridicule

There is a politically correct herd mentality that ascribes to the concept that objectivity is forsaken by medical companies that seek profit (and by their employees) because of 'conflict of interest.'

Also,

These overt restrictions on researcher communications in today’s climate of political correctness on COI are causing more than policy debates among various stakeholders....

In both these examples, concerns about conflicts of interest are deemed mere "political correctness." Thus, this is an appeal to ridicule.

Yet today there is a McCarthyesque reaction to the term, conflict of interest, with an unstated presumption of guilt until proven innocent.

Here instead the term of ridicule is "McCarthyesque."

Straw Man Fallacy

There is a politically correct herd mentality that ascribes to the concept that objectivity is forsaken by medical companies that seek profit (and by their employees) because of 'conflict of interest.'

This single sentence employed two fallacies for the price of one. I would challenge Dr Hirsch to provide a credible example that any thoughtful figure in the conflict of interest discussion has dismissed the objectivity of all for profit health care corporations, and all of their employees. He apparently has constructed a straw man argument which he has attributed to his opponents, one that is either to strike down than their real arguments.

Appeal to Authority

Previously, the president of the Association of American Medical Colleges emphasized that the term indicates a state of affairs and not a behavior, that COIs are ubiquitous, and that despite their inaccurate portrayal by the media, COIs do not indicate the occurrence of any improper behavior, much less scientific misconduct, analogous to a state of potential energy

If he said it, was he right? Is he still right today? Obviously, because someone with a distinguished title expresses an opinion does not mean it is true. Thus, this is an appeal to authority. (Note: since the reference appended to this sentence appears to have nothing to do with the content of the sentence, it is not even clear that the authority in question made such a statement. Link here.)

Appeal to Common Practice

Publication bias (preferential publication of studies with positive outcomes vs trials with negative, neutral, or ambiguous outcomes) has been reported for more than 2 decades,....

Publication bias clearly extends to government- and nonprofit-funded research....

The thrust here was clearly that publication bias is common and has been around for a long time, so why worry? This is an appeal to common practice, which equates a statement that a pheonomenon is common with the assertion that it is reasonable, justified, ethical, optimal, etc.

Special Pleading

For the 2008 article that was critical of Merck’s authorship practices by Ross, Hill, Egilman and Krumholz, the entire disclosure statement was, 'All of the authors have been compensated for their work as consultants at the request of plaintiffs in litigation against Merck & Co, Inc, related to rofecoxib.' Only in the middle of the Comment (Discussion) portion of the article was it mentioned that the authors had served as paid expert witnesses for plaintiffs’ attorneys in rofecoxib litigation. The terse disclosure statement seems at odds with JAMA’s stated policy in its Instructions for Authors that financial COI disclosure must be complete. Regardless, the information provided hardly conveyed that, as of January 2007, Krumholz had received more than $300,000 for his consulting from plaintiffs’ attorney Mark Lanier (no relationship to Mayo Clinic Proceedings Editor-in-Chief William L. Lanier, MD), which only became public in a letter to the editor of BMJ that responded to a previous article critical of Merck by Krumholz et al.

Krumholz’ remuneration seems substantial until it is compared to that of another coauthor of the JAMA authorship report,16 David Egilman. Egilman has testified for Mr Lanier and other attorneys in more than 100 tort cases (nearly always for plaintiffs) for approximately 2 decades and, by his own estimate, has earned $20 to $25 million for such testimony.

[Note: this discussion appeared in the midst of a long tirade against the editorial policies and practices of JAMA, especially in relation to controversy about the drug rofecoxib (Vioxx), the now withdrawn Merck Cox-2 inhibitor. Dr Hirsch apparently was responsible for Merck's publication policies about this drug. Further note that there are major questions about whether the figures supplied by Dr Hirsch are correct. Appended to the post in Dr Brody's blog post is a categorical denial by Dr Krumholz that he was paid, as asserted by Dr Hirsch, over $300,000, and evidence against the assertions by Dr Hirsch about Dr Egilman's pay.]

While Dr Hirsch alleged that the disclosures by the authors of this article were incomplete, he did not compare them to the disclosures made by authors of other articles in JAMA. In fact, I have never seen an article in JAMA which included disclsoure of dollar amounts, and could not find any such disclosure in spot checks of the latest issue.

On the other hand, here is the disclosure Dr Hirsch made in his own article:

Dr Hirsch was an employee at Merck & Co from 1988-2006 and managed the Medical Communications Department for clinical research publications from late 2001 to mid-2006. He currently is employed at a medical device and technology company that has no financial interest in any matters related to rofecoxib or the resulting tort litigation involving Merck & Co. Dr Hirsch owns mutual funds with stock from a variety of pharmaceutical and device companies, including Merck, and some shares of Merck and other medical product companies.

He did not disclose dollar amounts connected with any of these activities. He would not name his current employer on the grounds that it has no interest in rofecoxib and related litigation. However, his article is ostensibly about the broader issues of conflict of interest, authorship, etc which may relate to the interests of Becton Dickinson, which currently employs Dr Hirsch in the capacity of Worldwide Vice President of Medical Affairs, BD Diabetes Care. He did not name the "medical product companies" whose shares he owns.

Thus, Dr Hirsch argued that Dr Krumholz and Dr Egilman were wrong not to disclose the details of their financial arrangements with plaintiffs' attorneys (setting aside the likely inaccuracy of Dr Hirsch's contentions about the specifics of these arrangements), even though the detail they provided in their disclosures was similar to that provided by other JAMA authors, and even though Dr Hirsch did not find it necessary to himself disclose in such detail. Thus, Dr Hirsch was advocating a double standard, and in this case, his argument amounts to a special pleading, since the standard he advocated for others was not the same he felt obliged to uphold.


Appeal to Fear

[standards regarding COI] are beginning to affect the willingness of prominent researchers to interact with industry in any manner that involves even minimal compensation for their time and efforts.

Also,

There are serious negative implications for the future of medical product development if top academic researchers are shamed into ceasing any type of compensated interactions with industry.

Dr Hirsch implied that medical progress would be greatly endangered if industry no longer paid practicing physicians and full-time academics to work on the side, and that such payments would no longer be possible were COI disclosure requirements to be made more strict. Such dire warnings, without evidence to support them, amount to appeals to fear.

Summary

So Dr Hirsch has provided yet another example of an apologia for conflicted physicians and academics based on a panoply of logical fallacies. We have offered several other examples of fallacious defenses of conflicts of interest, compiled here.

It is sad to see logical fallacies so cavalierly employed. There frequent, sometimes strident use in current health policy suggest the need to better train health care professionals in logic and the use of evidence.

I am still awaiting a defense of the sorts of conflicts of interest that we frequently discuss on Health Care Renewal that is based on logic and evidence, but it may be that no one can produce such a defense.

Meanwhile, we continue to recommend that at the very least, medical academics, medical academic institutions, and other health care not-for-profits or NGOs should reveal in detail what payments they get from companies selling health care products or services, and how these payments could relate to the companies' marketing or lobbying efforts. In the US, some such disclosure would be mandated by the proposed "Sunshine" legislation now being considered by the US Congress. (By the way, note that this problem is hardly confined to the US, and needs global, not just American attention.)

However, physicians (at least physicians in full-time private practice, academic positions, and employed by mission-oriented not for profit organizations) should go further, and consider whether receiving industry money is worth the ongoing damage it does to our professionalism and our professional reputations. Medical schools, universities, health care foundations, disease advocacy groups, and other health care not-for-profits and NGOs should also go further, and consider whether receiving industry money is worth the ongoing damage it does to their missions, and their institutional reputations.

Post Title → Again, Defending Conflicts of Interest with Logical Fallacies

Bloggers Can Spread the Word, Just Not About the Sponsors' Competitors

The internet, social media, web 2.0 etc have changed how important health care issues are discussed. So, it is not surprising that big health care organizations are trying to use these new media to promote their messages. New media, however, are no more immune from the effects of conflicts of interest than are old media.

An article from corporate communications company Ragan.com about how the American Heart Association (AHA) is using bloggers to get people interested in a heart-healthy diet and exercise program illustrates how even "civilian" bloggers can get caught up in the web of conflicts of interest that pervades health care. The background is:

Keeping track of the conversations on the array of social media networks can gobble up your workday. So why not find someone else to do it for you?

The American Heart Association did just that, approaching four established bloggers with a proposal: Write about our new campaign, Go Red For Women: BetterU, and we’ll link to your blog from our site. BetterU is a 12-week online nutrition and fitness program to improve heart health among women.

The blogs appear to be working. They’ve helped drive traffic to Go Red/BetterU since the program’s June 1 launch.

It did seem that the AHA went to considerable effort to make sure they had recruited just the right bloggers.

The AHA researched potential candidates with the help of agencies Edelman PR and Edelman Digital. After a month-and-a-half, they settled on four bloggers: Joshilyn, Nyasha, Stacey, and Nadia.

The criteria: The bloggers had to be female, have an enthusiastic following, be diverse in age and ethnicity, and have a high Technorati rating. Most important, their content and advertising had to align with the association’s values, says Director of Marketing Anu Gandhi.

'You’re really ultimately picking a spokesperson for Go Red for Women and the larger American Heart Association,' [senior manager for cause communications Megan] Lozito says. 'That’s a really important process for us — that it be correct and that it be the right people. So we spent a lot of time getting to know those ladies and making sure our mission would be aligned.'

More interesting was the values with which the bloggers were supposed to align, particularly those relating to the program's corporate sponsors (see the logos at the bottom right of the BetterU web-site).

From there, the association brought the bloggers to the Dallas headquarters for a full health screening at The Cooper Institute, a photo session, a preview of the BetterU program, and some message training.

Although the BetterU bloggers got some message training in Dallas, Gandhi says AHA has been hands off when it comes to what they can and can’t say about the program.

The bloggers are asked to post once a week about BetterU and follow basic guidelines—no profanity, no defamation, no writing about nor condoning any medications or treatments. She says they also ask bloggers not to talk about competitors of AHA’s two national sponsors: Macy’s and Merck Pharmaceuticals.

I would suspect that the explicit instruction not to favor Merck's competitors would also remind the bloggers not not do say anything that might make the giant pharmaceutical company unhappy.

Eight weeks into the program, they haven’t had any problems.

'There are things we don’t want them to write, like profanity, but that’s also part of the vetting in the beginning,' Lozito says. 'We wanted to find people who believe in our mission, who speak to the same type of audience, but at the same time we want them to have their own flavor and own tone, because it’s a blog.'

So the bloggers recruited by the AHA may be happy, since they now have a big organization's web-site driving traffic to their blogs. The AHA may be happy, since the bloggers can spread the word about their BetterU program. I imagine the marketers at Merck may be happy too, since the bloggers have been warned about the need to keep the corporate sponsors happy. However, what may be good for all the parties in this transaction may not be so good for the general public, as another opportunity for uninhibited, honest discussion of health care issues has been lost.

This is an explicit example of the adverse effects of commercial funding of not-for-profit disease advocacy groups. Corporate sponsors may not expect anything as gross as advertising in return for their money. However, they may expect something more subtle, a generally favorable attitude toward the sponsor, at least the disinclination to say anything that might put the sponsor in a negative light. After all, politeness requires that we be nice to the people who are nice to us. But being nice to sponsors may not be so nice for the people that a health care not-for-profit organization is supposed to serve.

PS - for those who like science fiction, see the preview of the new version of "V," in which Anna, the leader of the Visitors, an invasion force disguised as human-appearing, benign aliens, warns her television interviewer,

Just be sure not to ask anything that would put us in a negative light.

Post Title → Bloggers Can Spread the Word, Just Not About the Sponsors' Competitors

BLOGSCAN - Merck Hired Elsevier to Create Fake Peer-Reviewed Medical Journal

You just can't make this stuff up. On the Respectful Insolence blog, Orac recounted how pharmaceutical giant Merck hired medical publishing giant Elsevier to create what appeared to be a peer-reviewed journal, but theAustralasian Journal of Bone and Joint Medicine really was just a marketing outlet. The goal was to market Fosamax and Vioxx. This is another bizarre variant on the stealth marketing theme, taken to quite an extreme. And the pharmaceutical companies wonder why people don't trust them?

ADDENDUM (4 May, 2009) - Dr Aubrey Blumsohn is back online on his Scientific Misconduct Blog, and noted the academic luminaries who were willing to serve on the editorial board of this fake peer-reviewed journal.

ADDENDUM (11 May, 2009) - See also comments on Laika's MedLibBlog.

Post Title → BLOGSCAN - Merck Hired Elsevier to Create Fake Peer-Reviewed Medical Journal

Harvard Medical Students Against Marketing in the Guise of Medical Education

An article by Duff Wilson in the New York Times this week provided a new look at the pervasiveness of financial relationships among academic medicine and health care corporations, and the beginnings of resistance to them.

The Scope of the Relationships

Many individual Harvard Medical faculty members receive tens or even hundreds of thousands of dollars a year through industry consulting and speaking fees. Under the school’s disclosure rules, about 1,600 of 8,900 professors and lecturers have reported to the dean that they or a family member had a financial interest in a business related to their teaching, research or clinical care. The reports show 149 with financial ties to Pfizer and 130 with Merck.

The rules, though, do not require them to report specific amounts received for speaking or consulting, other than broad indications like 'more than $30,000.' Some faculty who conduct research have limits of $30,000 in stock and $20,000 a year in fees. But there are no limits on companies’ making outright gifts to faculty — free meals, tickets, trips or the like.

Other blandishments include industry-endowed chairs like the three Harvard created with $8 million from sleep research companies; faculty prizes like the $50,000 award named after Bristol-Myers Squibb, and sponsorships like Pfizer’s $1 million annual subsidy for 20 new M.D.’s in a two-year program to learn clinical investigation and pursue Harvard Master of Medical Science degrees, including classes taught by Pfizer scientists.

Academic Medical Leaders' Defense of Their Relationships with Industry

Dr. Flier, who became dean 17 months ago, previously received a $500,000 research grant from Bristol-Myers Squibb. He also consulted for three Cambridge biotechnology companies, but says that those relationships have ended and that he has accepted no new industry affiliations.

So maybe it is not surprising that:

Dr. Flier says that the Harvard Medical faculty may lead the nation in receiving money from industry, as well as government and charities, and he does not want to tighten the spigot. 'One entirely appropriate source, if done properly, is industrial funds,' Dr. Flier said in an interview.

But,

That is in contrast to his predecessor as dean, Dr. Joseph B. Martin. Harvard’s rules allowed Dr. Martin to sit on the board of the medical products company Baxter International for 5 of the 10 years he led the medical school, supplementing his university salary with up to $197,000 a year from Baxter, according to company filings.

Dr. Martin is still on the medical faculty and is founder and co-chairman of the Harvard NeuroDiscovery Center, which researches degenerative diseases, and actively solicits industry money to do so. Dr. Martin declined any comment.

Note that we discussed Dr Martin's directorship of Baxter on Health Care Renewal here in 2006, and that we also found that he was on the board of biotechnology company Cytyc. Note also that we have discussed how serving on the board of a health care corporation can produce particularly intense conflicts of interest for academic medical leaders, since such board service implies not just warm and fuzzy feelings for the company, but "unyielding loyalty" to the financial interests of the company and its stockholders (e.g., see this post).

Unsurprisingly, faculty who have their own lucrative relationships with industry are all for more of the same:

Encouraging them is Dr. Thomas P. Stossel, a Harvard Medical professor who has served on advisory boards for Merck, Biogen Idec and Dyax, and has written widely on academic-industry ties. 'I think if you look at it with intellectual honesty, you see industry interaction has produced far more good than harm,' Dr. Stossel said. 'Harvard absolutely could get more from industry but I think they’re very skittish. There’s a huge opportunity we ought to mine.'

Note that Dr Stossel defended academic-industry "interaction," but did not explain why such interaction seems always to generate large money flows from industry to academic institutions and their individual faculty members. People can surely interact without paying each other.

Note further that Dr Stossel may have even more financial relationships with industry than appeared in the NY Times article. When we analyzed some of the logical fallacies Dr Stossel employed in favor of industry payments to physicians in 2007, we cited Stossel's attck on the rigorous conflicts of interest rules re-imposed on the US National Institutes of Health (NIH) in which Stossel had to disclose "having received consulting fees from ZymeQuest, owning stock options in ZymeQuest and Biogen, and having pending and issued patents, owned by Brigham and Women's Hospital, some of which are licensed to ZymeQuest." [Stossel TP. Regulating academic-industrial research relationships - solving problems or stifling progress? N Engl J Med 2005; 353: 1060-1065.] In this paean to a laissez-faire approach to conflicts of interest, Stossel also disclosed that he "is a member of the Board of Directors of Zymequest Inc, and the Scientific Leadership Advisory Board of Merck & Co. The author is a founding scientist of Critical Biologics Corporation and a consultant to Boston Scientific, Inc., and Gerson-Lehrman, Inc." [Stossel TP. Regulation of financial conflicts of interest in medical practice and medical research. Perspect Biol Med 2007; 50: 54-71. ]

Another defender of the status quo also has her own major relationships with industry:

Merck built a corporate research center in 2004 across the street from Harvard’s own big new medical research and class building. And Merck underwrites plenty of work on the Harvard campus, including the immunology lab run by Dr. Laurie H. Glimcher — a professor who also sits on the board of the drug maker Bristol-Myers Squibb, which paid her nearly $270,000 in 2007.

Dr. Glimcher says industry money is not only appropriate but necessary. 'Without the support of the private sector, we would not have been able to develop what I call our ‘bone team’ in our lab,' she said at a recent student and faculty forum to discuss industry relationships. Merck is counting on her team to help come up with a successor to Fosamax, the formerly $3 billion-a-year bone drug that went generic last year.

Note that Dr Glimcher now seems to view her role not as someone seeking to discover and disseminate the truth, but as someone seeking to develop commercial products. Again, maybe that is not surprising, since she is supposed to have an "unyielding loyalty" to the prominent pharmaceutical company on whose board she sits.

The NY Times article did not quote anybody in favor of financial relationships between academic medicine and industry who did not themselves have such relationships. I don't believe I have ever seen a defense of these relationships not authored by someone who was not already personally profiting from such relationships.

The Revolt of the Medical Students

While he documented how Harvard faculty who also lead huge pharmaceutical firms have no qualms about industry pouring money into medical academics, Mr Wilson found that medical students seem to have figured out the downside of being taught by pharmaceutical, biotechnology and device company employees:

In a first-year pharmacology class at Harvard Medical School, Matt Zerden grew wary as the professor promoted the benefits of cholesterol drugs and seemed to belittle a student who asked about side effects.

Mr. Zerden later discovered something by searching online that he began sharing with his classmates. The professor was not only a full-time member of the Harvard Medical faculty, but a paid consultant to 10 drug companies, including five makers of cholesterol treatments.

'I felt really violated,' Mr. Zerden, now a fourth-year student, recently recalled. 'Here we have 160 open minds trying to learn the basics in a protected space, and the information he was giving wasn’t as pure as I think it should be.'

Mr. Zerden’s minor stir four years ago has lately grown into a full-blown movement by more than 200 Harvard Medical School students and sympathetic faculty, intent on exposing and curtailing the industry influence in their classrooms and laboratories, as well as in Harvard’s 17 affiliated teaching hospitals and institutes.

They say they are concerned that the same money that helped build the school’s world-class status may in fact be hurting its reputation and affecting its teaching.

Note that the example, while anecdotal, shows how financial relationships could lead to biased education. The students have made surprising progress:

The Harvard students have already secured a requirement that all professors and lecturers disclose their industry ties in class — a blanket policy that has been adopted by no other leading medical school. (One Harvard professor’s disclosure in class listed 47 company affiliations.)

'Harvard needs to live up to its name,' said Kirsten Austad, 24, a first-year Harvard Medical student who is one of the movement’s leaders. 'We are really being indoctrinated into a field of medicine that is becoming more and more commercialized.'

David Tian, 24, a first-year Harvard Medical student, said: 'Before coming here, I had no idea how much influence companies had on medical education. And it’s something that’s purposely meant to be under the table, providing information under the guise of education when that information is also presented for marketing purposes.'

The students say they worry that pharmaceutical industry scandals in recent years — including some criminal convictions, billions of dollars in fines, proof of bias in research and publishing and false marketing claims — have cast a bad light on the medical profession. And they criticize Harvard as being less vigilant than other leading medical schools in monitoring potential financial conflicts by faculty members.

Unfortunately, many academics of my generation have become so used to making some extra dollars by working part-time for companies selling health care goods or services that they cannot see how these relationships have distracted them from the academic mission and their professional ideals. Maybe the rising generation of students, now living in a time when the consequences of arrogance, greed, and corruption among our leaders has become so apparent, will put professionalism ahead of personal enrichment.

Post Title → Harvard Medical Students Against Marketing in the Guise of Medical Education

On Wisconsin's "Talking Heads"

Last week, the Milwaukee Journal-Sentinel ran an investigative series on conflicts of interest affecting faculty at the University of Wisconsin medical school, one of the better known and more prestigious US state supported institutions. (The two main articles were "Doctors Face Pressure to Disclose All Side Pay," and "Drug Firms Wine, Dine and Pay Up for Doctors' Speeches.") Several of our fellow bloggers have discussed this excellent series already, including Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog, and Prof Margaret Soltan on the University Diaries blog.

So I will not go over the series in detail. Suffice to say that while the Journal-Sentinel's reporting is fresh, the problem may be tediously familiar to Health Care Renewal readers.

Although the University of Wisconsin (UW) is said to have an unusually stringent policy for "managing" conflicts of interest, the reporting requirements are vague, particularly about the financial magnitude of conflicts. The Journal-Sentinel report noted that some faculty who disclosed making only "more than $20,000" a year, a range prescribed by UW, made much more than that. Some faculty were paid by multiple companies. Some faculty were paid by medical education and communication companies (MECCs), which were presumably in turn paid by drug, device, or biotechnology companies whose identities were not disclosed. Some faculty were paid thousands to gave promotional talks which were not accredited as continuing medical education.

One orthopedic surgeon, Dr Thomas Zdelblick, disclosed yearly payments from device manufacturer Medtronic of over $20,000. The Journal-Sentinel reporters found he actually received as much as $400,000 a year in consulting payments, supposedly for working about eight days (that is, at a rate of $50,000 a day). A subsequent article in the Wall Street Journal found that Dr Zdelblick got even more than that. His total compensation from Medtronic was over $2 million a year, and as much as $4.6 million a year.

So again the picture is of a web of conflicts of interest affecting many faculty at one medical school. This adds to the now voluminous evidence that large numbers of medical academics have financially significant conflicts of interest. These financial arrangements are rarely fully disclosed, even as part of the university's attempts to "manage" them.

I spot-checked a few publications of two of the faculty named in the article, finding that they were no more explicit in their disclosures to readers of scholarly journals.

For example, Dr James Gern (who was, according to the Journal-Sentinel, a speaker and consultant for Merck from 2003 to 2007, who made about $35,000 - $70,000 a year for 28 days of work, and who was funded by Merck in a study of the effects of montelukast on people infected with the cold virus,) provided the following disclosures:
- In a 2008 single-author review of the linkages between viral respiratory infections and asthma(1), "the author has received honoraria from Merck Inc...."
- In a 2008 multi-author research paper on rhinovirus infections and asthma(2), he did not mention his relationship with Merck.

More strikingly, Dr Thomas Zdelblick, the orthopedic surgeon who got millions a year from consulting fees and royalties, provided the following disclosures:
- In a 2007 multi-author report of a clinical trial of the Medtronic Sofamor Danek cervical disc device(3), "the authors have received or will receive benefits for personal and/or professional use from Medtronic Sofamor Danek in relation to products named in this article."
- In a 2004 multi-author clinical research article on managing spine fractures,(4) "one or more author(s) has/have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript: e.g., honoraria, gifts, consultancies, royalties, stocks, stock options, decision making position."

Thus, while the usual approach of most universities to such conflicts of interest is to proclaim how they will "manage" them, this "management" often did not even include disclosure of the conflicts, and certainly not disclosure in detail sufficient for its audience to appreciate the degree to which the conflict might have biased seemingly authoritative academics.

Also, often financial arrangements between medical faculty and industry are proclaimed necessary to foster collaboration necessary to "innovation" and the development of miraculous new drugs and devices (for example, the Journal-Sentinel reported the Dean of the UW medical school said "consulting with the pharmaceutical industry can accelerate drug development and lead to job creation....") However, despite these ostensible benefits, many faculty seemed uncomfortable with and reluctant to talk about their relationships.
- Dr Barry Fox, who "worked for seven different drug companies in just one year," "would not discuss his drug company work...." When reached by telephone, he initially said, "I have nothing to hide," but when asked "what kind of work he did for a drug company, he said, 'I'm not comfortable with this conversation,' and hung up."
- Dr Zdelblick "did not return phone calls."
- 3 doctors who gave talks sponsored by drug companies would not discuss their work (see this side-bar article)

One doctor who gave approximately 20 drug talks did speak with the reporters, and was very frank.

It's promotional. We all know why we are there and what we are going to hear. You are going to hear about that drug.

We're just talking heads.

As the series noted, faculty and the university stand to benefit when drug and device companies pay doctors.

Medical schools have good reason not to prohibit such activities.... It [sic] allows them to pay their star faculty less because they can make substantial money working on the side for a drug or medical device company....

The school may also benefit, of course, when the companies who pay faculty on the side also give the school research or educational grants.

But while faculty and schools make money, they sacrifice the trust of community physicians, patients, and the public. As long as academics take big money from industry, often without much honesty about what they are doing, their independence will be suspect. Who knows when the talk, the article, the glitzy program is meant to disseminate the truth, or to help in marketing? Who knows whether the research study was manipulated? Who knows whether the policy pronouncement mainly would benefit vested interests?

Maybe academics and academic administrators would sleep better if they no longer had to dodge reporters' calls, twist rationalizations, or admit to being "talking heads." Those who used to depend on academic medicine to seek and disseminate the truth might sleep a lot better if it became independent once again.

References
1. Gern JE. Viral respiratory infection and the link to asthma. Pedi Infect Dis J 2008; 27: S97-103.
2. Jackson DJ, Gangnon RE, Evans MD et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med 2008; 178: 667-672.
3. Mummaneni PV, Burkus K, Haid RW et al. Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. J Neurosurg Spine 2007; 6: 198-209.
4. McDonough PW, Davis R, Tribus C, Zdelblick T. The management of acute thoracolumbar burst fractures with anterior coprectomy and Z-Plate fixation. Spine 2004; 29: 1901-1909.

Post Title → On Wisconsin's "Talking Heads"

Response from author of "The ADVANTAGE Seeding Trial"

In response to my earlier post "Merck scientific debate hits bottom" I received the following from one of the authors of the VIOXX seeding trial paper The ADVANTAGE Seeding Trial: A Review Of Internal Documents, Ann Intern Med 2008", Dr. David Egilman, MD, MPH.

I posted Dr. Egilman's opinions below at his request. My own thoughts follow.

Dr. Egilman also posted numerous documents to and from Merck's lawyer at this link. (The tone of some of those documents towards Dr. Egilman is particularly disturbing, such as the one here.)

------------------------------------------------------

From: David Egilman, MD, MPH
To: Healthcare Renewal

I am one of the authors of the "Seeding" paper.

Merck executive Dr. Jonathan M. Edelman, Executive director, Global Center for Scientific Affairs wrote:

There's no doubt that the ADVANTAGE clinical trial had a legitimate scientific purpose. That purpose was to assess the gastrointestinal tolerability of VIOXX compared to naproxen – a commonly used arthritis medicine with known tolerability problems – in the treatment of patients with osteoarthritis in a primary care setting, and for the first time allowed patients taking concomitant aspirin to participate.

Dr. Edelman's claim that ADVANTAGE was the first trial that permitted aspirin use with Vioxx is incorrect. Study 058, which was part of Merck's application for new drug approval submitted in November 1998, permitted the use of up to 325 mg of aspirin per day. ADVANTAGE only permitted up to 100 mg per day. Study 058 was a 30 week trial. ADVANTAGE was only a 12 week trial. Study 058 involved patients older than 80, comparing Vioxx to namebutone (another NSAID) and was completed in April 1998, about 10 months before ADVANTAGE enrolled a single patient. Study 078, the ghost-written Alzheimer’s trial also permitted aspirin, began in April 1998 and was scheduled to be completed by April 2000 before the end of the ADVANTAGE trial. More patients took low dose aspirin in the Vigor trial than the Advantage trial.

Further, ADVANTAGE was not designed to test the effect of aspirin on anything. Although aspirin was permitted, the examination of aspirin effects was not included as part of the study objective which Merck described: "[t]o assess the tolerability of rofecoxib (VIOXX) compared with naproxen for treatment of osteoarthritis." On the other hand, Merck Study 136 was designed to test the effects of concomitant aspirin and NSAID use. This study revealed that Vioxx offered no GI protection to low dose aspirin users who constituted the majority of potential Vioxx users.

By November 1998, when Merck sought FDA approval for an OA indication and three months before the ADVANTAGE trial enrolled any patients, Merck had already informed the FDA it had sufficient studies to prove Vioxx was efficacious for osteoarthritis patients. Merck's osteoarthritis trials (that it used to get FDA approval for use of VIOXX in osteoarthritis patients) had compared Vioxx to 3 other NSAIDS. The VIGOR trial, which tested Vioxx and naproxen in rheumatoid arthritis patients, started at the same time as ADAVANTAGE and used twice the dose of Vioxx than was used in ADVANTAGE. VIGOR was, therefore, a more valid scientific trial to determine relative safety of the two drugs.

This request for and subsequent approval meant that Merck could claim VIOXX was as effective for pain as naproxen. Beginning long before the Advantage trial Merck claimed Vioxx was safer than all NSIADS including naproxen.

While ADVANTAGE was the first study that compared Vioxx to naproxen in OA patients, Merck had completed trials comparing the two drugs in other pain patients.

It is for these reasons that the President of Merck Research Laboratories (MRL) Dr. Scolnick characterized ADVANTAGE as "intellectually redundant."

Merck wrote:

ADVANTAGE was a double-blind, randomized, controlled clinical trial with a legitimate scientific purpose designed to answer previously unanswered questions about the use of VIOXX in osteoarthritis in a primary care setting. It was not a seeding study.

Merck’s personnel called it a seeding trial internally but in an apparent effort to hide its true purpose wrote:

“I eliminated the reference to seeding. It may be a seeding study, but let’s not call it that in our internal documents.”

Merck apparently tried to make it look like a typical science-based clinical trial to mislead IRBs and journals. All seeding trials make some claim to some usually trivial scientific purpose. For example the question of whether or not Vioxx works better on people as a function of height is a scientific question. It is of course a trivial question. In this case Merck had studies that compared Vioxx to naproxen for pain control before the Advantage trial had started. Merck also had a larger trial that tested GI toxicity.

Merck wrote:

ADVANTAGE was important because although the earlier VIOXX clinical trial program provided extensive data on efficacy and safety, it did not include naproxen as a comparison Medication.

This is not correct. Merck had a study that compared Vioxx to naproxen for pain control before the Advantage trial started. This was presented to the FDA in the original New Drug Application and was published in October 1999.

Merck wrote:

The ADVANTAGE clinical trial was designed, conducted, analyzed, interpreted and published by the scientific department of Merck's U.S. Human Health (USHH) organization, Clinical Development (CDP), in conjunction with participating investigators. CDP was part of the Medical and Scientific Affairs department of USHH and was separate from the marketing department within USHH.

A more complete picture is:

USHH was the marketing division of Merck. It included sub-divisions including sales, marketing and a medical/scientific group called CDP. CDP performed “medical” studies that could be used by marketing to increase product sales. These studies were only conducted if favorable results could increase sales. They were not done to obtain new indications for drug use and Merck did not publish or provide the FDA with some of these studies (example 106).

Mr. David Anstice, a marketing executive with no apparent scientific training or background was the President of Merck's USHH division. In contrast Dr. Edward Scolnick, a physician/scientist of international renown, was the President of Merck’s research division which was called Merck Research Laboratories. Mr. Anstice the person ultimately responsible for the Advantage trial testified:

Q. I understand that. All I'm saying is, this is the study [Advantage trial] that was initiated and conducted by marketing, right?
A. Yes, by doctors in marketing.

A picture being worth a 1000 words I provide the Merck graphic for the organization of the Advantage trial:



Here is the power point description of marketing’s role in the Advantage trial:



While the marketing division of USHH set the study “objectives” CDP was in charge of the technical aspects of study implementation.

Further proof that ADVANTAGE served little scientific purpose is the fact that Merck had already claimed that Vioxx was safer than and as effective as all NSAIDS including naproxen prior to the initiation of the ADVANTAGE.

Merck did not rely on any ADVANTAGE results to make any claim about Vioxx efficacy or safety to the FDA. The lack of scientific purpose behind ADVANTAGE is demonstrated by the fact that Merck had withheld the ADVANTAGE results from its application to the FDA that requested a label change that would allow them to claim Vioxx was safer than naproxen. Merck only produced the results after the FDA made numerous oral and written requests for the safety data discovered during the trial.

Merck claims Advantage produced important scientific information:

In the end, ADVANTAGE showed a different gastrointestinal profile between VIOXX and naproxen that was unaffected by concomitant use of aspirin. This was an important medical result for physicians. In addition to measuring the GI tolerability of VIOXX, investigators also monitored patients for adverse events, which were required to be submitted to the FDA. Therefore, in ADVANTAGE, Merck was further evaluating any potential risks of VIOXX.

In fact the trial that Merck performed to test the effect of concomitant aspirin and Vioxx use (136) showed that aspirin use thwarted Vioxx’s GI advantage. (Gastroenterology. 2004 Aug;127(2):395-402.) The conclusion Merck reached based on the Advantage result was wrong precisely because Advantage was not designed to test this question. This conclusion was based on data mining.

Merck wrote:

We also want to underscore that the scientific purpose of ADVANTAGE was properly disclosed to physicians-investigators, participants, and institutional review boards, and Merck's business interests were clearly understood.

Merck never disclosed the marketing purpose of the trial which included the fact that Marketing “set objectives.”

Merck accuses the authors of "bias.”

In this open letter to the editors of The Annals of Internal Medicine, Merck would like to put in perspective the latest article by four authors who served as paid consultants to plaintiffs' lawyers in the VIOXX litigation against Merck. We are troubled by the biased article, which contains numerous inaccuracies, and wonder about the motivation behind this attack on Merck's scientific excellence and integrity.

Merck writes that the authors were “plaintiff witnesses” and “cherry picked” documents. As far as I know, all litigation ended about a year ago. None of the authors were paid on a contingency basis, the authors received no compensation from plaintiffs to work on the papers we have written and none of the authors are working on any Vioxx litigation at this time.

If money motivation equates to bias then it is Merck and its representatives who suffer from this problem. The same cannot be said of Merck or its representatives because while the authors have nothing to gain Merck’s future earnings depend, in some measure, on its reputation for honesty.

Merck does not explain how any theoretical bias impacted on the paper. They have not come forward with contradictory documents or testimony.

The authors agree that all the documents should be made public so readers can decide for themselves if we “cherry picked.” Merck, and Merck alone, continues to block the release of the documents.

Merck would not allow us to cite documents that showed that Advantage investigators were accused of fraud and at least one was convicted. Some of this data was deleted from the published paper but readers and editors were never informed of these problems.

It should be noted that eight Vioxx patients had heart attacks during the ADVANTAGE trial compared to one patient on naproxen. Merck never informed any of these patient volunteers of the cardiovascular risks of Vioxx before or after the trial although the informed consent stated that Merck would pay for treatment of drug related side effects. Unfortunately for some, this would have been funeral costs.

Merck wrote:

It is unfortunate that the authors and journal editors chose not to contact Merck before finalizing these publications. Had any of these individuals contacted Merck, factual errors could have been avoided.

I contacted Merck's main trial lawyer Ted Mayer and provided Merck an opportunity to comment on another paper related to the Advantage trial before it was submitted for publication. I did not send a pre-publication copy to plaintiff lawyers. Mr. Mayer provided comments and i included his comments in the final version.

Merck then complained about my contact to Mr. Mayer to Judge Higbee and requested that she sanction me for contacting their lawyer and then insisted that I make no further contact with them.

-- David Egilman

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My own thoughts on all of this are as follows:

The lessons of the Annals article are clear. The scientific community and the public are simply fed up with cavalier practices in the biomedical industry. While the article may affect remaining VIOXX litigation as pointed out here, it also should have an necessary "cleansing effect" on drug R&D.

It was not clinicians and scientists outside the industry who earned it the public's animosity. It was, and continues to be, the industry itself. As Roy Poses observed, there cannot be evidence based medicine if the evidence is distorted by commercial zealotry. I think the public recognizes this.

Further, marketing personnel have no place in pre-approval, pre-marketing scientific studies such as clinical trials. If they have a scientific role, it is perhaps in post-marketing studies, especially post-marketing surveillance for adverse effects. The latter is a function the pharma industry performs poorly.

Even in that latter domain, there must be honesty and transparency, characteristics with which the biases of marketing and its leaders (e.g., towards maximizing sales) may interfere.

Merck's responses to this new Annals article seem the antithesis of science. Instead, the responses appear to be right out of the political and legal warfare playbook (where logical argument prevails - except when presenting logical fallacy is to the advantage of the protagonists) ...

The response has been this:

• ignore the arguments and evidence [in this case, emails and documents from Merck itself],
  
• issue an ad hominem attack,
  
• issue slogans ("litigation in the name of science"),
  
• present a Red Herring as a distraction,
  
• issue accusations of bias,
  
• issue accusations of cherry picking,
  
• issue accusations of the authors taking evidence "out of context", etc.

and finally:

• produce no context or new evidence of your own, hoping the above tactics will make that unnecessary.
  

All that's seemingly missing are ... puppets.

Merck seems to expect the "courtesy" of being allowed to be a participant in any issues written about its conduct, as if the authors of this paper are its employees who under employment policies must permit any pubs they produce to be reviewed internally for approval. I believe the company's executives forget that their authority ends at the front gate.

It is also an odd and even arrogant request, especially considering the way the authors' evidence (Merck's own emails and documents) was essentially ignored in the responses, and the insinuations promulgated against the authors as serving plaintiff's lawyers -- which also implies that scientific integrity and the interest of patients is not their motivation.

As I mentioned in my earlier post, this is classic ad hominem and is insulting to authors in my opinion, as well as insulting to any clinician or scientist. Why would anyone want to provide a company that acts in this manner the courtesy of pre-publication involvement in investigative journalism?

Another issue I find interesting is noted in the limitations section of the paper where it is stated that:

... we did not identify, despite an exhaustive and systematic search strategy, documents detailing discussions between the marketing and research divisions, nor could we identify documents describing contracts between Merck and collaborating companies.

As well as the Annals editor's obervations that:

... despite the large body of documents searched by the authors, they discovered few details about exactly how Merck's marketing division carried out ADVANTAGE.

This is surprising. From an information science standpoint, it would not be unreasonable to believe there might be more related to this trial of a major drug in emails or powerpoints or other documents. This document sparsity could mean that the documents did not exist, but it also raises a speculative question about the document corpus produced in Discovery.

Could "inconvenient documents" have selectively been eliminated from the corpus of documents before it was released, and therefore not be present in the corpus of documents the authors searched? Could the documents the authors did find represent ones that were "missed" by some weeding out effort?

Finally, I believe the entire tenor of Merck's responses - ignoring evidence, stating the trial was "published in a peer reviewed journal" as a Red Herring and a justification of its legitimacy while ignoring Sox & Rennie's (the Annals editors) accompanying commentary Seeding Trials: Just Say "No" , belitting the authors, etc. - is very disturbing.

From "Seeding Trials: Just Say No":

No one told Annals the true purpose of ADVANTAGE. We learned about it when we received a letter to the editor from Dr. David Egilman, who was a consultant to the plaintiffs' attorneys in the civil suits against Merck. He had access to publicly accessible trial documents, which included Merck employees' e-mail messages that disclosed the true intent of the ADVANTAGE trial ... The article provides clear evidence that the intent of ADVANTAGE was to increase prescriptions of Vioxx (the study outcome of greatest interest to Merck seems to have been Vioxx prescribing rates) ... The documents do tell us that deception is the key to a successful seeding trial.

When I review NIH grant applications, if I suspect deception I will mention it to the study section leaders, and I can assure that if deception is verified higher up the chain, that application will not get funded (at the very least). I can also assure that legitimate medical journals do not willingly publish studies involving deception.

Merck's responses to the Annals article seem to represent a belief that the public (laypeople and physicians) are stupid and gullible.

This is not science, and is not a path to a return to the corporate greatness and respect that Merck once enjoyed and had earned.

Finally, a Red Herring of my own:



-- SS

Post Title → Response from author of "The ADVANTAGE Seeding Trial"