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All the shenanigans that went on in the course of Merck's marketing of the now withdrawn Cox-2 inhibitor non-steroidal anti-inflammatory drug Vioxx have provided grist for the Health Care Renewal mill since 2005.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Merck & Co. agreed to settle shareholder lawsuits over the withdrawn Vioxx painkiller by strengthening its drug-safety procedures, appointing a new chief medical officer and paying $12.2 million in legal fees.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

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.

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 na�vet� 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/