Giant GSK Settlement Provides Reminder of the Pervasiveness of Stealth Marketing

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

In the largest settlement involving a pharmaceutical company, the British drugmaker GlaxoSmithKline agreed to plead guilty to criminal charges and pay $3 billion in fines for promoting its best-selling antidepressants for unapproved uses and failing to report safety data about a top diabetes drug, federal prosecutors announced Monday. The agreement also includes civil penalties for improper marketing of a half-dozen other drugs.

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

No individuals have been charged in any of these cases.

Thus, how well even such a large settlement will deter future wrong-doing is not clear.

Nonetheless, the documents released with it provide good documentation about how pervasive systematic, deceptive stealth marketing campaigns have become in health care. 

In particular, the official "complaint" filed by the US Department of Justice emphasized all these elements in the stealth marketing of paroxetine (Paxil, Seroxat in the UK) to adolescents.

Manipulation of Clinical Research

We have frequently discussed how health care corporations, particularly pharmaceutical, biotechnology and device companies, now sponsor  the majority of clinical research.  Their control of the design, implementation, analysis and dissemination of clinical research allows manipulation that increases the likelihood that the results will be favorable to their vested interests, usually the products and services they sell. 

We have previously discussed the manipulation of Study 329 to promote the marketing of Paxil (look here and here).  However, the US DOJ document makes these concerns more official.  It included:

Manipulation of Study Endpoints

Study 329 was a randomized controlled trial of Paxil vs imipramine vs placebo for depression in adolescents. The two primary endpoints pre-specified to the US Food and Drug Administration were "the degree to which a patient's Hamilton Rating Scale for Depression ('HAM-D') total score changed from baseline"; and "the patient's 'response' to medication, as defined as (a) a 50% or greater reduction in the patient's HAMD-D score, or (b) a HAM-D score of less than or equal to 8." However, initial analysis by GSK failed to show that Paxil improved either of these two end-points. The company concluded "it would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of [Paxil]."

So the analysis emphasized secondary outcomes, the "Study 329 investigators later added several additional efficacy measures not specified in the protocol. Paxil separate statistically from placebo on certain of these measures." Adding numerous post-hoc measures increased the likelihood of finding a difference on at least one due to chance alone.

Manipulation of Data

Initial analysis of the data suggested that patients given Paxil experienced 11 serious adverse events, including five that appeared related to suicidal ideation or action. When the FDA later reexamined the data, "upon closer examination the number of possible suicide-related events among the Study 329 Paxil patients increased beyond the five patients GSK described in the JACAAP article as having 'emotional lability.' While collecting saftey information for the FDA, GSK admitted that there were four more possible suicide-related events among Paxil patients in Study 329. In addition the FDA later identified yet another possible suicide-related event in the Study 329 Paxil patients, which was also not among the 11 serious advents listed in the JAACAP article. Thus, altogether, 10 of the 93 Paxil patients in Study 329 experienced a possible suicidal event, compared to one in 87 patients on placebo. This is a fundamentally different picture of Paxil's pediatric safety profile than the one painted by the JAACAP article...." 

Manipulation of Dissemination

The report describing the results of Study 329 (Keller MB, Ryan ND, Strober M et al.  Efficacy of paroxetine in the treatment of adolescent major depression: a randomized controlled trial.  J Am Acad Child Adolescent Psychiatry 2001; 40: 762-772.  Link here. ) was written under the control of GSK. "In April 1998, GSK hired Scientific Therapeutics Information, Inc (STI) to prepare a journal article about Study 329. GSK worked closely with STI on the article by providing a draft clinical report to 'serve as a template for the proposed publication.'"

The published report of Study 329 "mischaracterized the results." "Although the ... article identified the study's two primary endpoints in the abstract, the article did not explicitly state that Paxil failed to show superiority to placebo on either of the primary efficacy measures." Also, "the article did not explicitly identify the two protocol-specified primary outcome measures - or that Paxil failed to show superiority to placebo on these two measures. Instead the article claimed that there were eight efficacy measures and that Paxil was statistically superior to placebo on four of them." In addition, "while the article listed the five protocol-defined secondary endpoints, the text of the article omitted any discussion regarding three of the secondary measures on which Paxil failed to statistically demonstrate its superiority to placebo and instead focused on the five secondary measures that GSK added belatedly and never incorporated into the Study 329 protocol. The article claimed that these finve secondary measures had been identified 'a priori,' therefore incorrectly suggesting that all secondary endpoints had been part of the original study protocol." In other words, the final published articles contained multiple outright falsehoods about the drug's efficacy that exaggerated that efficacy.

Furthermore, initial analysis showed that patients given Paxil had more serious adverse events than others. An initial draft of the study article stated, "serious adverse events occurred in 11 patients in the paroxetine group, 5 in the imipramine group, and 2 in the placebo group." These included "headache during down-titration(1 patient), and various psychiatric events (10 patients): worsening depression (2); emotional lability (e.g., suicidal ideation/ gestures, overdoses), (5); conduct problems or hostility (e.g., aggressiveness, behavioral disturbance in school) (2); and mania (1)." As noted above, the number of suicide related events was actually double that noted in this draft as "emotional lability."  However, the published version of the report "falsely state[d] that only one of the 11 serious adverse events in Paxil patients was considered related to treatment...."  Nor did it mention the true number of events related to suicidal ideation or action.

The article only "listed at most five possibly suicidal events among Paxil patients, brushed those off as unrelated to Paxil, and conclude that treating children with Paxil was safe."

Later, GSK marketing materials described the results of the study thus,

This 'cutting-edge,' landmark study is the first to compare efficacy of an SSRI and a TCA with placebo in the treatment of major depression in adolescents. Paxil demonstrates REMARKABLE Efficacy and Safety in the treatment of adolescent depression."

Thus the conrol exerted by GSK over the published article, despite its apparent academic authorship, enabled it to promote a drug that was not efficacious and had major adverse events as remarkably safe and effective, a totally deceptive result that would mislead any health care professional who used the article to guide clinical practice. 

Suppression of Clinical Research

GSK sponsored two other studies of Paxil in pediatric populations, Studies 377 and 701. As stated in the Department of Justice's Criminal Complaint against GSK,

GSK Did Not Publicize the Results of Studies 377 and 701
43. GSK learned the results of Study 377 in 1998 and the results of Study 701 in 2001. Paxil failed to demonstrate efficacy on any of the endpoints of either study.
44. GSK did not hire a contractor to help write medical articles about the results of Studies 377 and 701, as it had with Study 329.
45. GSK did not inform its sales representatives about the results of Studies 377 and 701.

Thus, GSK managed to conceal the fact that the majority of the studies it sponsored about Paxil used for adolescent patients showed no evidence that the drug worked, again seriously distorting the evidence-base on which clinicians made decisions, and doubtless leading to the use of a dangerous, ineffective drug by numerous vulnerable patients.

Bribing Physicians to Prescribe

GSK's sales representative reflected in their call notes their use of money, gifts, entertainment and other kickbacks to induct doctors to prescribe GSK drugs....

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

For example, in or about 2000 or 2001, GSK used 'Reprint Mastery Training Programs' or 'RMTS' to further promote drugs by purporting to pay physicians to train sales representative to review reprints of studies. Although the training was purportedly for the representatives, in fact, the sales force was already familiar with the materials. GSK typically paid physicians $250 to $500 to review the reprints.

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

The sales force bribed physicians to prescribe GSK products using every imaginable form of high-priced entertainment, from Hawaiian vacations [and] paying doctors millions of dollars to go on speaking tours, to tickets to Madonna concerts.

Use of Key Opinion Leaders as Disguised Marketers

GSK also created a group of national 'key opinion leaders' ('KOLs') who were paid generous consulting fees. GSK selected many of these physicians based on their prescribing habits and influence within the community and used the speaker fees paid to these physicians to induce and reward prescribing of GSK's products. GSK used these individual to communicate marketing messages focused on the drug's marketing campaigns at the time, including off-label uses. Some physicians on GSK's speaker's board have been paid more than a million dollars for speaking on behalf of the company and recommending its drugs.

Thus key opinion leaders were paid specifically to market drugs, and as a reward, a bribe for prescribing drugs.

Consulting Fees as Kickbacks

In general,

In order to induce physicians to prescribe and recommend its drugs, GSK paid kickbacks to health professionals in various forms, including speaking or consulting fees, travel, entertainment, gifts, grants, and sham advisory boards, training,....

In particular,

During 2000 and 2001 at least, GSK also utilized events termed 'advisory boards' or consultant meetings and forums to disseminate its promotional message. Although these boards were purportedly composed of 'thought leaders' for the purpose of obtaining advice from the physicians, in fact, the 'advisory boards' were little more than promotional events coupled with financial inducement to prescribing and influential physicians.

Also,

GSK typically paid the physician between $250 and $750 to attend each local 'advisory' meeting. The payments did not reflect the value of services. The physician was not required to do anything but show up. GSK had no legitimate business reason to hire thousands of 'advisors' to 'consult' with the company about a single drug.

Manipulation of Continuing Medical Education

GSK also used so-called CME and CME Express programs and other sham training for marketing purposes, and to promote off-labe uses for the GSK prescription drugs.

Furthermore,

These CME programs purported to be independent eduaction free of company influence, but in fact functioned as GSK promotional programs disguised as medical education. GSK maintained control and influence over the purportedly independent CME programs through speaker selection, and influence over content and audience, among other things. Although third party vendors were usually also involved, they served only as artificial 'firewalls' that did not insulate the program from GSK's influence.

Summary

The legal documentation of the GSK settlement demonstrated how one drug company used an integrated, systematic campaign incorporating deception and bribery to sell drugs. Its elements included manipulation and suppression of the clinical research it sponsored, paying key opinion leaders to be disguised drug marketers, outright payments to physicians to prescribe drugs, and manipulation, again using payments to physicians, of supposedly independent continuing medical education. 

Note that while I summarized the elements of the stealth marketing campaign to sell Paxil, particularly for use in pediatric patients, the US government complaint also documents similar activities used to sell other drugs.  Furthermore, other stealth marketing campaigns have come to light through legal action, and many other instances of manipulation and suppression of clinical research, use of KOLs as disguised marketers, kickbacks and bribes, and manipulation of CME have been documented.

This means that any claims that:
- commercially sponsored clinical research provides clear, unbiased data that should drive clinical decisions
- health care professionals and academics paid as consultants by commercial health care firms are not influenced by these payments, and can provide clear, unbiased opinions
- commercially sponsored medical education provides clear, unbiased teaching
unfortunately must be viewed with extreme skepticism. This is particularly unfortunate given that most clinical research is now supported by commercial sponsors, and the majority of influential academics in medicine get some form of payments from the health care industry (look here).

Of course, there are some physicians who consult for commercial firms who actually provide clinical or scientific advice or assistance, and some commercially sponsored activities are honest. But we must wonder what garden path all those advocates for increasing industry "collaboration" to promote "innovation," and who regard conflicts of interest as "inevitable" and "manageable" are taking us down (e.g., look here and here).

Although the current settlement will require a huge payment, as I have said many times before (as early as 2008, here), do not expect such settlements to deter future bad behavior like that listed above.  The cost of the settlement will actually be spread among all company shareholders, all company employees, and likely patients and taxpayers.  However, the settlement will entail no specific negative consequences to the people who authorized, directed, or implemented the bad behavior.  In particular, executives whose remuneration was swollen by proceeds from the sales of affected drugs, and the health care professionals who willingly accepted what the US Attorney called bribes will not pay any sort of penalty.  The bad behavior listed above was doubtless personally very profitable for some people.  Unless people who indulge in such behavior face the possibility of penalties worse than their expected gains, expect such bad behavior to continue.

In fact, as the New York Times reported,

critics argue that even large fines are not enough to deter drug companies from unlawful behavior. Only when prosecutors single out individual executives for punishment, they say, will practices begin to change.

'What we’re learning is that money doesn’t deter corporate malfeasance,' said Eliot Spitzer, who, as New York’s attorney general, sued GlaxoSmithKline in 2004 over similar accusations involving Paxil. 'The only thing that will work in my view is C.E.O.’s and officials being forced to resign and individual culpability being enforced.'

True health care reform would strive to eliminate important conflicts of interest affecting clinical research and medical education.  Specifically, it would prevent corporations that sell health care products or services from controlling clinical research meant to evaluate these products or services.  It would seek to eliminate serious conflicts of interest affecting health care professionals.  Finally, it would prevent vested interests from controlling medical education.  Not that I expect any such reform in the near future, it would be too threatening to those who have personally benefited from the current system.

Hat tip to Dr Howard Brody whose Hooked: Ethics, Medicine and Pharma blog scooped me on the details of the settlement relevant to study 329.

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

"More Marketing Than Science" - An Anonymous Confession About Deceptive Marketing Published in the British Medical Journal

The British Medical Journal just published an anonymous article by a pharmaceutical company insider that explained once again how pharmaceutical companies turn research studies, apparently scholarly articles, and medical education into stealth marketing efforts.  (See Anonymous.  Post-marketing observational studies: my experience in the drug industry.  Brit Med J 2012; 344: 28.  Link here.)

We have previously discussed examples of health care corporate insiders confessing their individual efforts to turn medical research and education into marketing.  For example, peruse this.  We have also discussed how documents made public through litigation have revealed marketing plans for specific drugs that used apparently academic, educational, or scholarly publications and venues to market without revealing this transformation.  For example, see the Neurontin marketing plan (see post here), and the Lexapro marketing plan (see post here).  We have also discussed numerous examples of manipulation of particular research studies by those with vested interests, and outright suppression of studies whose results did not favor such vested interests.

Yet I suspect majorities of health care academics and professionals, health care policy makers, and the public at large do not realize, or would not admit that the evidence base for making health care decisions, and the general academic and professional discourse has been so corrupted.  So it is worthwhile to review once again how an insider summarized this corruption.

Research Studies Designed Primarily as Marketing Vehicles

In general, the anonymous author suggested that at least some studies were done for marketing, not scientific purposes:

some of the studies I worked on were not designed to determine the overall risk:benefit balance of the drug in the general population. They were designed to support and disseminate a marketing message.

Whether it was to highlight a questionable advantage over a 'me-too' competitor drug or to increase disease awareness among the medical community (particularly in so called invented diseases) and in turn increase product penetration in the market, the truth is that these studies had more marketing than science behind them.

Furthermore, the studies were supervised not by physicians or scientists, but by marketers in the marketing department,

Although the medical department developed the publication plans, designed the study, performed the statistical analysis, and wrote the final paper (which when published was passed on to marketing and sales to be used as marketing material), the marketing team responsible for that product were directly involved in all stages. They also closely supervised the content of other educational 'scientific' materials produced in the medical department and intended for potential prescribers. Instructions from marketing to the medical staff involved were clear: to ensure that the benefits of the drug were emphasised and the disadvantages were minimised where possible.

Manipulation of Research Design, Implementation, or Analysis

The author described how the marketers manipulated research studies so they would produce the results desired from a marketing perspective, regardless of their underlying truth,

Since marketing claims needed to be backed-up scientifically, we occasionally resorted to 'playing' with the data that had originally failed to show the expected result. This was done by altering the statistical method until any statistical significance was found. Such a result might not have supported the marketing claim, but it was always worth giving it a go to see what results you could produce. And it was possible because the protocols of post-marketing studies were lax, and it was not a requirement to specify any statistical methodology in detail. On the other hand, the studies were hypothesis testing (such as cohort studies, case-control studies) rather than hypothesis generating (such as case reports or adverse events reports), so playing with the data felt uncomfortable.

Other practices to ensure the marketing message was clear in the final publication included omission of negative results, usually in secondary outcome measures that had not been specified in the protocol, or inflating the importance of secondary outcome measures if they were positive when the primary measure was not.

So to summarize, the marketers would control the statistical analyses, promoting multiple analyses to attempt to come up with the "right" result that would support the marketing message (although the more kinds of analyses one tries, the more likely one is likely to come up with false results by chance alone). Presumably the marketers did not care whether or not the results were really true, which is perhaps why even they felt "uncomfortable" in some circumstances.

They would also foster the suppression of negative results, and the dredging of data for extra outcome measures when analysis showed no advantage in terms of the real primary outcomes. Suppression of negative results could be viewed as plain lying. Deliberate analysis of multiple end-points again risks identifying random error as true results.

The Role of Key Opinion Leaders

The author described how key opinion leaders, that is, health care professionals thought to be especially influential on practice or policy, were hired to become marketers presumably without revealing this intention.

Every big international observational study had a large advisory board. This was critical since the success of a newly launched drug in the market would depend on how many key opinion leaders were part of the study. Not only would they add credibility to the results, but they would also be key in influencing decision makers and other prescribers. In regional studies with thousands of patients, the study’s advisory board was formed by at least one key opinion leader from each country in that region, ensuring that areas important in terms of possible sales were covered. The contributions of the key opinion leaders to the study were always positive, but in my experience more directed towards designing new studies to answer their specific clinical questions rather than critically appraising our results and conclusions. In general, the relationship was amicable. We took them to the best hotels and restaurants during our advisory board meetings, and they appeared as authors in our research. Later, they would act as the company’s 'ambassadors,' giving conferences, teaching doctors, or talking to the media about the benefits of the drug.

Note that even the anonymous author could not bring him or herself to call the key opinion leaders salespeople, or marketers, but used the ambiguous wterm "ambassadors." Nonetheless, the role of key opinion leaders described would clearly be that of marketers or salespeople. However, it is extremely doubtful that any of these KOLs felt they had to declare that they were paid salespeople when presenting at conferences, teaching doctors, or talking about the media.

I would suggest that their actions would therefore fit Transparency International's definition of ethical corruption, "abuse of entrusted power for private gain." The KOLs are entrusted to be professional, and in many cases, scholarly. Using a professional or scholarly guise to act as a salesperson appears to be abuse of that entrusted power, in my humble opinion. In nearly every case, KOLs are paid, often handsomely, by the companies whose products they are selling. Thus, key opinion leaders acting as described by the anonymous author appear to be ethically corrupt.

Summary

The evidence of unethical marketing practices by commercial health care firms is mounting. Although I am most familiar with evidence from the US, there is mounting evidence that these practices are global, often done by companies that are not US based, and meant to influence practice and policy world-wide.

As the evidence mounts, it becomes increasingly clear that many such marketing practices are corrupt, at least in an ethical sense. Whether they may break laws in particular countries is a question for someone else.

The latest BMJ article is a reminder how skeptical the shrinking group of health care professionals who do not have conflicts of interest, are not biased in favor of particular products, and who put patients' interests first must be about ALL published research, scholarly publications, and apparently educational activities. Advocates of true evidence-based medicine must be extremely careful to try to use the least biased and manipulated parts of the evidence-base.

The mounting evidence suggests that at a minimum, all research reports, scholarly articles, media reports, conferences, and educational programs should provide full, detailed disclosure of all conflicts of interest. Perhaps having to make a declaration like "I am paid 50,000 Euros a year by the marketing department of company X to help market drug Y" before a supposedly educational talk would make some health care professionals think twice about such relationships.

However, even such detailed disclosure may not be sufficient to hamper marketing practices that now appear overtly corrupt. In my humble opinion, it is time to consider a global ban on the funding or influencing of human research by companies and other organizations which stand to gain financially according to the results of the research, or whose products and services are subject of such research. It is also time to consider a global ban on the funding or influencing of health care education by such organizations.

However, so many people are making so much money from the current practices that I doubt such proposals would get much support, or even public notice beyond this humble blog.

Know-Nothing, or Industry Shill? You Be The Judge.

I have not been writing much the past few weeks due to other concerns, and will probably not write much this summer.

However, I have been commenting on various posts on other blogs.  One resultant thread stands out as yet another example of a likely industry shill or sockpuppet defending the state of health IT, oddly at a blog on pharma (same blog as was the topic of tmy post "More 'You're Too Negative, And You Don't Provide The Solution To The Problems You Critique', This Time re: Pharma").

Industry-sponsored sockpuppetry is a form of stealth marketing or lobbying, through discreditation of detractors, although in a perverse form.

The following exchanges meet the sockpuppetry criteria once pointed out by business professional and HC Renewal reader Steve Lucas in 2010 in a post about an industry sockpuppet caught red-handed through IP forensics here:

... In reading this thread of comments I have to believe [anonymous commenter moniker] "IT Guy" is a salesperson. My only question is: Were you assigned this blog or did you choose it? We had this problem a number of years ago where a salesperson was assigned a number of blogs with the intent of using up valuable time in trying to discredit the postings.

In my very first sales class we learned to focus on irrelevant points, constantly shift the discussion, and generally try to distract criticism. I would say that HCR is creating heat for IT Guy’s employer and the industry in general.

I find it sad that a company would allow an employee to attack anyone in an open forum. IT Guy needs to check with his superiors to find out if they approve of this use of his time, and I hope he is not using a company computer, unless once again this attack is company sanctioned.

In the hopes that continued exposure of this nonsense can educate and thus help immunize against its effects, I present this:

At "In the Pipeline", a blog on medicinal chemistry (the science of drug making) and other pharma topics, a rebuttal to a claim that over 500,000 people (not 50K) might have died due to VIOXX was posted entitled "500,000 Excess Deaths From Vioxx? Where?"

That 500K possibility appeared on a UK site 'THE WEEK With the FirstPost' at "When half a million Americans died and nobody noticed."  The author of the FirstPost piece started out by raising the point made by publisher Ron Unz that life in China might be more valued than that in the U.S., where major pharma problems and scandals generally meet what this blog calls "the anechoic effect."  (In China, Unz noted, perpetrators of scandalous drug practices actually get arrested and suffer career repercussions.)

FirstPost notes:

ARE American lives cheaper than those of the Chinese? It's a question raised by Ron Unz, publisher of The American Conservative, who has produced a compelling comparison between the way the Chinese dealt with one of their drug scandals – melamine in baby formula - and how the US handled the Vioxx aspirin-substitute disaster ... (Unz) "The inescapable conclusion is that in today's world and in the opinion of our own media, American lives are quite cheap, unlike those in China." 

Not to argue to merits of the order of magnitude-expanded VIOXX claim, which I disagree with, but having concern for the general state of ethics in biomedicine in the U.S., I posted the following comment at the comment thread of the rebuttal post at "In the Pipeline" at this link:

6. MIMD on May 30, 2012 11:38 AM writes...

While I agree the VIOXX numbers here are likely erroneous, the point of the cheapening of the value of American life is depressingly accurate.

For instance, look how readily companies lay people off, ruining them, and perhaps forcing them out of the workforce forever.

Also, currently being pushed by HHS is a medical device for rapid national implementation known to cause injury and death. The government is partially financing it to the tune of tens of billions of dollars, probably with Chinese money no less.  [Either that, or with freshly-printed money adding to the trillions of $ in our deficit - ed.]

There are financial penalties for medical refuseniks (non-adopters).

However, FDA, the Institute of Medicine and others readily admit in publication thay have no idea of the magnitude of the harm because of lack of data collection, impediments to information diffusion and even legal censorship of the harms data. In effect, we don't even know if the benefits exceed the harms, and FDA and IOM admit it. FDA in fact refers to the known injuries and deaths from this device as "likely the tip of the iceberg."

Perhaps to some it's no longer a big deal if people are injured and/or die in data gathering for this medical enterprise.

E.g., see "FDA Internal Memo on H-IT Risks", and the Inst. of Medicine report in the same issues here.

It's all for the greater social good, they might say.

 

The following anonymous reply ensued:

10. Watson on May 30, 2012 1:47 PM writes...

@6 You keep using that word - "device" - I do not think it means what you think it means

 

I replied:

11. MIMD on May 30, 2012 3:48 PM writes...

 #10

'medical device' is the term chosen by FDA and SMPA (EU).
But that's a distraction from the points I raise in the linked post about the experiment.

To which this confused misdirection came forth from the ether:

12. Watson on May 30, 2012 4:46 PM writes...

The linked article is discussing the poor state of "medical device records" because of a lack of uniform specifications with respect to Health Information Technology, i.e. how these technologies code data and the challenges of making the data obtained uniform across a wide variety of implementations and vendors. [Erroneous, incomplete misdirection - ed.]

It seems that the concern, far from being that Health Information Technology is "killing" people, is that the Medical Device Records may contain duplicate reports for adverse health events because of health care providers encoding the data more than once for each event.  [What in the world? - ed.] This problem with replication exists because there are different health record systems where this data needs to be input, and perhaps the same patient uses different physicians who have different systems, but all of which are required to report adverse events. [I have little idea what this even means - ed.]

In other words, "Health Information Technology" is not some monolithic "device", and your conflation of "HIT" which is more properly an abstract term with the "devices" which are used to generate some forms of patient data is in my view the real distraction. [The "real" distraction from the ethical issues of the HIT experiment is terminology about medical devices?  Misdirection again from the ethical issue, and of a perverse nature - ed.]

Yes, some of the "devices" (a blood pressure monitor for example) may have underlying issues, which the FDA regulations for "medical device records" are designed to identify. The FDA, as a governmental entity has no constitutional power to mandate certain devices or implementations are to be used.  [Now we're in la-la land of misinformation and distraction- ed.] The power that the FDA does have is to inspect that the manufacturer of a device keeps appropriate medical device records (e.g. a lot of syringes, or a batch of formulated drug) and addresses any complaints about the device to the satisfaction of the FDA.

My replies:

17. MIMD on May 31, 2012 8:51 PM writes...

#12

It seems that the concern, far from being that Health Information Technology is "killing" people, is that the Medical Device Records may contain duplicate reports for adverse health events because of health care providers encoding the data more than once for each event

Yes, fix just that little problem and then the problems with clinical IT are solved! (Actually,I'm not even sure what you're referring to, but the evidence is that fixing it as you suggest is the cure.)  [Sarcasm - ed.]

The FDA, as a governmental entity has no constitutional power to mandate certain devices or implementations are to be used.

You are also right about FDA. They were completely toothless even in this situation.  [Sarcasm again - ed.]

18. MIMD on May 31, 2012 9:10 PM writes...

#12

In other words, "Health Information Technology" is not some monolithic "device", and your conflation of "HIT" which is more properly an abstract term with the "devices" which are used to generate some forms of patient data is in my view the real distraction.

Those who conducted the Tuskegee experiments probably felt the same way.

It's all about definitions, not ethics, and not data - which FDA as well as IOM or the National Academies, our highest scientific body, among others, admits, as in the linked posts in #6, is quantitatively and structurally lacking on risks and harms.

I don't really mean to laugh at you, not knowing how little you really know about the Medical Informatics domain, but you bring to mind this Scott Adams adage on logical fallacy:

FAILURE TO RECOGNIZE WHAT’S IMPORTANT
Example: My house is on fire! Quick, call the post office and tell them to hold my mail!

And with that, I move on, letting others enjoy the risible comments from surely to follow! :-)

I could not have been more correct.

In typical industry shill/sockpuppet fashion comes this, with clear evidence of a not-so-clever liar which I've bolded:

19. Watson on June 1, 2012 12:35 AM writes...
@18

I read the articles you originally linked to, and my comments were based upon trying to interpret your meaning from those selections. I worked in the industry and had to deal with GMP, and had to make sure to follow all of the guidelines with respect to medical device manufacturing and electronic records. I understand the terminology very well. Luckily, I never had to deal with "health IT", but I did have to pore over enough pages of Federal Register legalese to know that what is sufficient is not necessarily what is best.  [Right.  See below - ed.]

Is that risible enough for you?

The link that you provided in @17 was a much more concrete example, and if you had referenced it in your original post, would have cleared up much of the confusion that I (and I assume @9) faced in understanding what it was you were trying to convey. It would have been useful if you had explained which device or devices you were talking about. If you had more than conjecture to back up the Chinese money trail, and if you had provided an example of a company that has been damaged by being a refusenik, those would have supported your argument as well. [Continuing haphazardly with the irrelevant as a distraction in an attempt to shift the focus from the ethical issue of nationally implementing HIT in a relative risk-information vacuum, having weakly conceded the main argument's been lost - ed.]

Straw man and ad hominem fallacies are pretty transparent around here, and I wish you the best with both. [Another attempt at diversion - ed.]

I assure you that I recognize what's important, that I have ethics, and that I care about people having reliable healthcare. [This seems a form of post-argument-lost attempt to seize the moral high ground - ed.]

I then point out the nature of what is likely a bold-faced lie.  Someone who's read the Federal Register in depth would likely know FDA's authority is not a "Constitutional power", as bolded below: 20. MIMD on June 1, 2012 6:44 AM writes... @19 The FDA taxonomy of HIT safety issues in the leaked Feb. 2010 "for internal use only" document "H-IT Safety Issues" available at the link in my post #6 is quite clear: - errors of commission - errors of omission or transmission - errors in data analysis - incompatibility between multi-vendor software applications or systems This is further broken down in Appendices B and C, with actual examples. Both this FDA internal report and the public IOM report of 2011 (as well as Joint Commission Sentinel Events Alert on health IT of a few years ago, and others) make it abundantly clear there is a dearth of data on the harms, due to multiple cultural, structural and legal impediments to information diffusion. Yes, it's in the linked IOM report at #6 entitled "Health IT and Patient Safety: Building Safer Systems for Better Care". See for instance the summary pg. S-2 where IOM states about limited[ed] transparency on H-IT risk that "these barriers to generating evidence pose unacceptable risks to safety." Argue with them, not me. Back to my original point: national rollout of this medical device (whatever you call it is irrelevant to my point, but see Jeff Shuren's statement to that effect here) under admitted conditions of informational scarcity regarding risks and harms represents a cheapening of the value of patient's lives. Cybernetics Over All. As to your other misdirection, spare me the lecture. It's not ad hominem to call statements like "The FDA, as a governmental entity has no constitutional power to mandate certain devices or implementations are to be used" for what they are - laughable (and I am being generous). FDA's authority is statutory, not written in the Constitution. Same with their parent, HHS. To get quite specific, on human subjects experimentation, which the H-IT national experiment is, the statutory authority for HHS research subject protections regulations derives from 5 U.S.C. 301; 42 U.S.C. 300v-1(b); and 42 U.S.C. 28. [The USC or United States Code is the codification by subject matter of the general and permanent laws of the United States.  HHS revised and expanded its regulations for the protection of human subjects in the late 1970s and early 1980s. The HHS regulations on human research subjects protections themselves are codified at 45 CFR (Code of Federal Regulations, aka Federal Register) part 46, subparts A through D. See http://www.hhs.gov/ohrp/humansubjects/guidance/. - ed.] A real scientist would have known things like this before posting, or have made it their business to know. Tell me: are you in sales? Not to point fingers, but with your dubious evasion of the ethical issue that was the sole purpose of my post, and your other postings using misdirection and logical fallacy to distract, you fit that mindset. You certainly don't sound like a scientist. Any med chemist worth their salt (pun intendend) would have absorbed the linked reports and ethical issues accurately, the first time. I then pointed out I've moved this 'discussion' to the HC Renewal Blog, as it is not relevant per se to pharma, the major concern of In the Pipeline. Industry shill/sockpuppet (as in the perverse example at this link) or just a dull, ill-informed but opinionated person who happens to read blogs for medicinal chemists, where layoffs have been rampant in recent years, takes issue with my attacks on those practices, and defends health IT like a shill? You be the judge. Whether a shill or know-nothing contributed the cited comments, it is my hope this post contributes to an understanding of pro-industry sockpuppetry. -- SS

The Texas TMAP Trial as Illustration of a Systematic Stealth Marketing Campaign

Before it was abruptly ended by a sudden settlement for $158 million, the trial in Texas of a suit alleging unethical marketing of the drug Respirdal (risperidone) by the Janssen subsidiary of Johnson and Johnson opened yet another window on organized stealth marketing campaigns in health care. (Note that we first discussed this case here in 2006, and that this trial and the case was ably covered in detail on the 1BoringOldMan blog.) 

Even so, given all the recent attempts to dismiss critics of the pharmaceutical industry as "pharmascolds," (e.g., here), and to otherwise uphold the current status quo in our dysfunctional health care system, I thought it would be useful to rediscuss this case to show how systematic stealth marketing threatens the ideals of rational, evidence-based health care.

Evidence-based medicine may simply be viewed as medicine based on evidence and logic tempered with humanity. A slightly longer definition is practice based on the best evidence from clinical research derived from systematic searches, critically reviewed, used to maximize individual patients' benefits and minimize their harms according to their values.

In contrast, brief summaries of sworn testimony during the trial, and of a key report by an expert witness suggested how a commercial health care organization, in this case, the Jennssen subsidiary of Johnson and Johnson, could organize a stealth marketing campaign to promote practice based on deception and falsehoods, entangled in illogic and emotional and psychological manipulation. This was all done to market a product which could not so easily be supported by evidence and logic.

Deception and Falsehoods: Suppression of Medical Research

A Bloomberg report of the last day of the trial showed how the Respirdal stealth marketing campaign used the now classic mechanism of suppression of medical research:

Johnson & Johnson officials hid three studies showing some patients using Risperdal developed diabetes while claiming the antipsychotic drug didn’t cause the disease, a witness testified.

As early as 1999, Johnson & Johnson’s Janssen unit had researchers’ findings that about half the patients taking Risperdal in a study comparing its risks to those of Eli Lilly & Co.’s Zyprexa antipsychotic drug developed diabetes after a year on the medication, Joseph Glenmullen, a psychiatrist and Harvard Medical School instructor, told a Texas jury yesterday.

That study concluded Risperdal caused 'medically serious weight gain' that led study subjects to develop diabetes, Glenmullen testified in the trial of the state of Texas’s lawsuit over Janssen’s marketing of the drug. At the same time, Janssen salespeople were telling doctors that researchers concluded the drug didn’t cause the disease, Glenmullen added.

In particular,

Glenmullen, testifying as an expert for the state, told jurors Janssen officials didn’t turn over Study 113, which found Risperdal posed a higher diabetes risk than Zyprexa, to the U.S. Food and Drug Administration when regulators began probing links between anti-psychotic medications and the disease in 2000.

The drugmaker also didn’t turn over the results of two other later studies that found Risperdal and Zyprexa posed comparable diabetes risks to the FDA.

Suppression of research is a severe threat to evidence-based medicine because it can severely bias the clinical evidence base on which it depends.
Deception and Falsehood: Ghostwriting

A summary of the 86 page report by Professor David Rothman commissioned by the Texas Attorney General published in the Houston Press provided this example of ghostwriting:

A member of J&J's Speakers Bureau, [University of Texas Professor of Psychiatry Dr Alexander] Miller collected at least $82,000 from Janssen and its contractors. He declined to comment for this story, saying he may be called as a witness in the lawsuit.

Miller was a 'guest author' for one of Janssen's ghostwritten articles. Upon receiving the manuscript, Miller wrote, 'Yes, I am happy to be included as a co-author. I made a few minor edits and comments in the manuscript.'

In addition, another article in the Houston Press summarizing the issues before the trial provided this overview of the ghostwriting process:

As described in the AG's expert witness report, a company called Excerpta Medica was hired to draft some of Janssen's Risperdal articles.

In 2003, according to Rothman, Excerpta Medica issued 'Risperidone Publication Program Status Reports,' indicating that 30 of the 145 articles to be published had authors listed as 'to be determined.'

Rothman also examined what he considered a signature ghostwritten piece meant to boost Risperdal's pediatric profile; the study is included in the 2010 parameters.

Rothman cited a barrage of e-mails between Excerpta Medica and J&J in crafting the article. At one point, an Excerpta Medica employee wrote, 'It would be very helpful to receive some guidance in relation to the flow, format and subject in this paper and whether you think this is too marketing oriented or not, in order to prepare a next draft. Besides that we would like [to] have some suggestions for external authors on this paper. Maybe [a] U.S. and a European KOL? Your input will be much appreciated.''

The article eventually appeared in a 2007 volume of the European Journal of Child and Adolescent Psychiatry. For a lead author, J&J scored a heavy hitter: Dr. Peter Jensen, former associate director of child and adolescent research at the National Institute of Mental Health, and the founding director of the Center for the Advancement of Children's Mental Health at Columbia University. Now with the Mayo Clinic, Jensen declined to comment for this story.

This indicates the scope of this particular ghostwriting initiative: 145 articles were planned.  Thus, ghostwritten articles could comprise a major proportion of the apparently scholarly literature relevant to Risperdal.  Ghostwriting is fundamentally deceptive because it allows marketing to appear in the guise of scholarly work.  Ghostwritten reviews can deceptively shift the focus from the questions that need to be addressed by the evidence-based process to benefit patients to those whose answers would benefit marketers.


Deception and Falsehoods: Key Opinion Leaders
Emotional and Psychological Manipulation: Creation of Conflicts of Interest

An important element of most stealth marketing campaigns is the creation of key opinion leaders.  These are academics or professionals who can promote products in the guise of unbiased expertise. 

A summary of the 86 page report by Professor David Rothman commissioned by the Texas Attorney General published in the Houston Press provided the example of Dr Steven Shon:

As the head of the state's mental health agency, Shon was perhaps Janssen's most crucial key opinion leader; his influence in pushing ­Risperdal was invaluable.

He accepted at least $47,000 from Janssen and its medical ghostwriter, Excerpta Medica, and signed an agreement to be a member of Johnson & Johnson's Speakers Bureau. Rothman writes, 'The medical director of the state's mental health agency should not be serving as an official spokesperson for a pharmaceutical company whose product state agencies are purchasing.'

The company paid for his trips across the country, and even overseas, to promote ­Risperdal as a safe and effective medication. (But the romance between Janssen and Shon was not without its bumps; Shon would get 'upset' if the checks he accepted from Janssen were made out to the MHMRA instead of directly to him. Apparently, those were more difficult to funnel into his personal account.)

Shon retired in 2005, allowing him to collect his taxpayer-funded pension. He moved to Las Vegas, where he's the director of psychiatry for a mental health and substance abuse clinic called Harmony Healthcare.

Shon was so influential that Janssen grew paranoid and possessive when it learned that other companies sought his partnership as well. When J&J employee Yolanda Roman heard that Eli Lilly had flown him to their headquarters on a private jet, she wrote, "Steve I suppose is enjoying the vast attention and response he can command from Industry...Obviously, Steve has the right to be served by all Industry, let's hope he remains fair [and] balanced and remembers who PLACED HIM ON THE 'TMAP' MAP."

Meanwhile, another employee busted out the caps-lock to warn that "WE WILL NOT LET LILLY OR PFIZER PREVAIL WITH OUR MOST IMPORTANT PUBLIC SECTOR THOUGHT LEADER."

Similarly, a Bloomberg report of Dr Shon's trial testimony included:

Johnson & Johnson’s Janssen unit paid a Texas mental health official to speak around the U.S. about state guidelines on prescribing antipsychotic drugs that gave preference to medicines like the company’s Risperdal, the official said.

Steven Shon accepted honorariums to fly to Arizona, Florida and New Jersey to discuss Texas guidelines developed in 1999 advising doctors that a newer class of drugs like Risperdal were a “first choice or option” for schizophrenia, he testified today in state court in Austin.

Also,

Attorneys for Jones questioned Shon, who served as medical director of the Texas Department of Mental Health and Mental Retardation until he involuntarily retired in 2006.

Shon testified that he served on Janssen advisory boards, was a board member of a Janssen publication called 'Mental Health Issues Today' and was a continuing medical education speaker in programs sponsored by the company.

Shon was asked about six trips in which he got honorariums of $3,000 from Janssen to discuss the TMAP project. In several cases, he kept those payments, he said.

In testimony yesterday, a Texas Medicaid investigator said Shon signed several consulting agreements with Janssen, and the company paid him $47,587 over several years.

Dr Shon's value to Janssen derived from his position as the respected leader of the state's mental health agency. While he was apparently paid by Janssen marketers who saw him as an ally, his marketing was all the more effective because it seemed to come from an unbiased expert. As such it was deceptive.

The Institute of Medicine report on conflicts of interest defined them as "a set of circumstances that creates a risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest." The report, and indeed much of the discussion of conflicts of interest in health care assumes that most secondary interests are "-within limits - legitimate and even desirable goals." For example, an academic physician who also was a basic scientist could be paid by a pharmaceutical company to do a specific assay on samples used in research. In that case, the payments could conceivably create a risk that the academic's professional judgment in a clinical setting would be unduly favorable to the products of the company. However, the relationship hardly seems intended to cause such a bias. Notions that conflicts of interest are "inevitable" but "manageable" may stem from consideration of conflicts of interest like this.

However, conflicts of interest deliberately created as perverse incentives may be much more consequential, and as this example shows, perhaps not rare. It appears that Janssen paid Dr Shon not to do some task that was unrelated to how he fulfilled his primary entrusted responsibilities as director of mental health, but in order to influence how he fulfilled them. We have noted previous examples in which corporate marketers consider paid key opinion leaders as sales people (see posts here and here). Such conflicts are deliberately created so that the recipient of payments uses his or her entrusted responsibilities to serve the vested interests of the payer may be deceptive, as noted above.  Furthermore, by being intended to induce changes in how the payee performs his or her primary responsibilities, these conflicts are particularly likely to lead to abuse of these entrusted responsibilities. Given that the Transparency International definition of corruption is abuse of entrusted power for private gain, we need a new and more incisive term to described this variety of conflicts of interest.

The motivation of key opinion leaders by created conflicts of interest can result in powerful manipulation of the key opinion leaders, but more importantly of their audience. 

Emotional and Psychological Manipulation: Intimidation

Another Bloomberg report included testimony about how someone who attempted to blow the whistle about the Respirdal stealth marketing campaign was intimidated:

Allen Jones testified yesterday in state court in Austin, Texas, that he was an investigator in the Pennsylvania Office of Inspector General in 2002 when he looked into an unregistered bank account run by Steven Fiorello, the pharmacist. Fiorello was on a Pennsylvania committee weighing whether to require doctors to give priority to newer, more expensive drugs like Risperdal in state-funded treatment of mental-health patients, Jones said.

Jones, 57, said he found a $4,000 check from J&J’s Janssen unit to Harrisburg State Hospital that was sent “\'to the attention of' Fiorello. The check covered a Fiorello trip to New Orleans to discuss Pennsylvania’s drug guidelines. Another check for $1,766 to the hospital account was sent 'in care of' of Fiorello, Jones said. Fiorello controlled the account and didn’t register it with the state, Jones said.

'The account was used to deposit money from drug companies,' Jones said yesterday in the trial’s third day of testimony. 'There were real problems here. On many levels, the account was improper.'

Janssen also paid $2,000 directly to Fiorello as an honorarium for his speaking at a company-sponsored event in 2002, Jones said. Jones said he followed the money trail and explored efforts by Janssen to promote, on a state-by-state basis, Texas guidelines favoring drugs like Risperdal. The funds sent to the hospital account helped pay travel expenses for programs related to setting up the Texas guidelines in Pennsylvania, he said.

The state adopted the guidelines that favored Risperdal in 2003, Jones said.

Note that this testimony appears to be about yet another KOL paid to promote guidelines that would in turn promote the marketing of Respirdal. So this is yet another case of a conflict of interest apparently deliberately created to influence the individual's primary responsibility.

However, then

Jones said his boss told him to ease off his probe. He said he was told, 'Stay away from the drug companies. This is a personnel issue. Stay away from the drug companies, stay away from TMAP.


Jones said his boss said, 'Drug companies write checks to both sides of the aisle. Stay away from it.' His boss told him that 'morally and ethically I was correct, but politically, this was dead.'

Jones said that later he was removed as the lead investigator from the case, and he was 'marginalized completely.' He continued to pursue the case on his own time, and spoke to the New York Times for a story that ran Feb. 1, 2004. He said he was fired for talking to the newspaper.

So Jones was intimidated to the extent that he lost his job. Note further that the implication is that this intimidation stemmed from yet more conflicts of interest created by Janssen, payments to politicians. This underlines how stealth marketing campaigns become complex systems.

Note further that in retrospect, Jones' complaints were deemed true by a court of law and a state commission:

Fiorello, once the chief pharmacist for Pennsylvania’s public welfare department, was convicted in December 2008 of felony conflict-of-interest charges for taking payments from drug companies, including Janssen and Pfizer Inc. He was sentenced to 18 months of probation and fined $3,000. He also paid more than $27,000 in civil fines after the Pennsylvania Ethics Commission cited him.

In a sense, intimidation and created conflicts of interest are two sides of the same coin.  Both involve the deliberate imposition of incentives, either positive or negative.  These incentives are designed to further marketing aims and organizational interests, not to improve patient care or public health, or advance science.  Thus they are powerful tools of emotional and psychological manipulation.
Summary

Note that even the brief summaries of trial evidence suggested how systematic the campaign was, and how within it, the elements of deception and falsehoods (instead of evidence), and emotional and psychological manipulation (instead of logic and humanity) were predominant. This should be added to previous discussion of stealth marketing campaigns, including such examples as that of Neurontin here).

Stealth marketing campaigns are complex examples of how behavior meant to further vested interests may directly threaten evidence-based practice, physicians' professionalism, and ultimately patients' and the public's health.

There have been many calls (e.g., see recent posts here and here) for increased "collaboration" among health professionals and academics and industry.  Often they are justified by the need for "innovation," while resulting conflicts of interest are deemed "manageable."  The current examples show how the vested interests of health care organizations operating within a laissez faire, anything goes environment may make such collaboration poisonous.

Guest Blog: Mediator, symptom of a broken French system

Elena Pasca blogs at PharmaCritique, and is a member of the Fondation Sciences Citoyennes.  She discusses the pharmaceutical industry in France, and relationships among that industry and physicians and the government.  She demonstrates that the issues we discuss on Health Care Renewal are global.

Introduction

A few weeks ago, the French health minister proposed a new law to improve pharmacovigilance, drug evaluation and transparency issues. It will be discussed in September by the Parliament. Let’s see what the actual situation is in France.


The Médiator (benfluorex) scandal raises not only pharmacovigilance issues. The first question that comes to one’s mind is how could the drugmaker Servier, who knew about its dangers, keep Médiator on the market for 30 years, despite the repeated alerts and the withdrawal of other amphetamines from the same drug class?

The answer goes far behind pharmacovigilance dysfunction. Médiator is not an isolated case, but an epiphenomenon of structural failures on every organisational level of the French health care, drug evaluation and health information system. The entire system is broken, and there still are dozens of defective and too risky drugs on the French market.

Most relevant for US readers is not to list all the alerts starting in the seventies with the fenfluramines. It’s to understand that the entire system was organised in order to be as industry friendly as possible. And the announced measures aren’t going far enough to change this fact.

Private profits before public health

In July 2009, president Nicolas Sarkozy decorated Jacques Servier with the Légion d’honneur and criticised again what he considered to be a huge amount of administrative regulations in the pharmaceutical branch. For him as the former business attorney of Servier, whose electoral program stipulated “cleaning business law”, too much regulation means less business, less competitive French drugmakers.

President Sarkozy’s health policy clearly favours the pharmaceutical industry, especially Sanofi-Aventis. His choice of Alzheimer disease as the first public health issue is not naïve. Sarkozy’s brothers have multiple conflicts of interests and ties with Sanofi-Aventis, the insurance industry and the organisations and institutions involved in the health care of the elderly, as I pointed out in an investigation published on Pharmacritique. And Sanofi hasn’t yet any me-too from the anticholinesterase drug class largely prescribed to Alzheimer patients, despite repeated proof of their ineffectiveness and of their side effects.

As a direct result of Sarkozy’s policy, publicly funded research will be exploited through public-private partnerships to produce immediate results – and neglecting fundamental research bringing new knowledge and thus real therapeutic progress. The intellectual property policy clearly favours private profits.

The European research policy has the same aims: the Innovative Medicines Initiative is clearly oriented toward “innovation” meant as competitive advantage for the pharmaceutical industry, not as an improvement in disease understanding and treatment. The exploitation of public research for private corporate profits has been criticised by the Helmholtz Gemeinschat (union of the German public research centres).

A few weeks ago, 98 European NGOs and organisations wrote an open letter criticising the Common Strategic Framework for EU Research and Innovation Funding and asking for a responsible European research policy: “Public Research should benefit Society, not Big Business”.

Conflicts of interests are everywhere, corrupting the entire health care system

In France, except for two journals (Prescrire and Pratiques), the entire medical press is completely dependent on drugmakers and their advertising. Especially family physicians receive such journals for free. They include no disclosures, so there’s no possibility to sort out advertising from information. Most of those journals are owned by a trust whose leader is Gérard Kouchner, brother of the former health minister Dr. Bernard Kouchner. (See this post on PharmaCritique.)

To this misinformation by the sponsored press has to be added another source of bias: continuing medical education [CME] is funded up to 98% by the pharmaceutical industry. And up to 97% of self-employed physicians still receive drug reps and consider them to be a comfortable, if not reliable, information source.

As long as I can go back, all health ministers have had conflicts of interest. In a hearing by the Parliament’s committee on Médiator, Gérard Kouchner was questioned about his journals’ silence about the risks of this drug and about the book written by the whistleblower Dr. Irène Frachon. He answered those journals are serious, no odd news, no sensationalism… As if informing physicians about severe side effects of a drug and experts’ conflicts of interests and drugmaker influence wouldn’t be serious enough…

The state can’t control conflicts of interest and implement oversight because the medical corporation is well organised (trade unions…) and opposes every reform or measure restricting its freedom. And the medical lobby knows how to use its political influence. Commercial interests, entrepreneurship, industrial funding (research, travel, professional activities, CME…) are organised and encouraged by the Order of Physicians. Despite of the 1994 law prohibiting gifts, dining, wining and lodging continues. Daily corruption is widely accepted, since it is approved by the Order of Physicians… Organised medicine’s unusually strong influence over France’s health care system is well described by Marc Rodwin in his book “Conflicts of Interest and the Future of Medicine. The United States, France, and Japan” (Oxford University Press 2011).

The French FDA – AFSSAPS - is financed up to 80% by the pharmaceutical industry, via taxes. Up to 70% of the AFSSAPS experts have conflicts of interest. But the real percentage must be higher, because the recently introduced disclosures aren’t verified, and omissions or false declarations aren’t prosecuted. In a 2007 report, AFSSAPS officials had to acknowledge their strategy of “managing” conflicts of interests wasn’t a success...

The more drugs the agency approves, the more money it gets. Drugmakers exploit competition existing among European agencies to earn more money, and they also know which country will easily approve their drugs, opening the door for a homologation by the EMA (European Medicines Agency). When a drugmaker knows this or that drug is defective, approval is not even attempted in the US, but only in certain European countries. Why risk a defeat that could damage its image?

For example, during the swine flu epidemics, some vaccine makers haven’t asked for approval in the USA, because their vaccines contain new technologies (MDCK cells, adjuvants such as squalen) they wanted to “test” on European people first, before submitting them to the FDA. The German independent journal Arznei-Telegramm revealed the existence of a market analysis counselling this strategy (2009; 40: 85-7).

None of the swine flu vaccines commercialised in Europe were approved in the US. The same laboratories produced different vaccines, and new technologies were used instead of the classical ones, in the name of the… emergency. Since then, hundreds of cases of narcolepsy were reported, especially among children and teen-agers, as a side effect of GSK’s Pandemrix (containing squalen).  (See this post on PharmaCritique.)

Complete lack of information about drugs and their adverse reactions

Pharmacovigilance in France is rather pharmacosomnolence: the AFSSAPS reacts late after others western countries when it comes to puttin a defective drug off the market. On the opposite, it easily accepts homologation demands. If you compare the drugs available in France and the USA, you’ll find lots of drugs rapidly withdrawn or rejected by the FDA, or even unknown in the US: etoricoxib (Arcoxia), nimesulid, rimonabant (Acomplia), lots of progestagens, veraliprid (Agréal)… After the FDA decision, it took 11 years to take Distilbene (DES) off the French market. Vioxx continued for years on the French market after its withdrawal in the US. Mediator was withdrawn 1997 in the US, 2010 in France. And so on.

In a 2008 article, Donald Light highlighted “Europeans are kept in ignorance about dangerous drugs” (Rev Prescrire 2008;28(297):553). He gave several examples of drugs such as aprotinin, olanzapine, etoricoxib, sleeping drugs… where safety alerts have been made public by the FDA and relayed by the US media, and compared this information with the silence in France. Before the Médiator scandal, the French media weren’t interested in drug safety, conflicts of interest, corruption, bias in the medical research…

But it’s even worse. The public has no access to the official prescribing information, reserved to physicians paying for the Vidal (equivalent of the Physicians’ Desk Reference), edited by a private company… I compared the prescribing information of lots for drugs available in the US and in France, produced by the same drug companies, approved in the same indications. The information is so different, as if they weren’t the same drugs…

France has few relevant regulations and laws, so the country is a paradise for the pharmaceutical industry, and for industries, lobbies and business in general. There’s no FOIA, no way for watchdogs – even for official watchdog agencies – to get real information. In a 2007 report, the IGAS (General Inspection of Social Affairs, France’s OIG) only could give estimations, based on extrapolations, about lobbying and marketing expenses of the pharmaceutical industry.

Consumers International published the results of a 2008 conducted inquiry about drugmakers’ legal obligations in the US compared to Europe. 12 drugmakers answered and all agreed the requirements aren’t at all the same, in regard of transparency and disclosures, in regard of complete information about drugs, and so on.

So why would drugmakers give an information no one requires and no one wants?

Pharmacovigilance is subordinated to drug approval, and until recently, patients couldn’t report side effects. A pharmacovigilance official told me that even now, adverse reaction reports without documentation and follow-up aren’t always counted. The regional pharmacovigilance centres don’t forward them to the AFSSAPS.

There’s no transparency about the specific phases of the drug evaluation system, in terms of risk/benefits, and there’s no evaluation at all in terms of cost/effectiveness and economic efficiency. The Haute Autorité de Santé was created for this kind of quality and economic efficiency evaluation, like the German IQWIG and the British NICE. But everything it does is officialise drugmaker marketing claims and “assess” the improvement in the actual benefit. But it’s only a formal assessment, and I don’t remember of a drug dismissed by this agency because of insufficient improvement…

In January 2011, president Sarkozy appointed Pr. Jean-Luc Harousseau as the head of the Haute Autorité de Santé, despite all the recent promises to reform the system and fight against the conflicts of interest of experts and officials. Pr. Harousseau is the perfect example of French opinion leaders with political and industrial interests that become experts and leaders of national institutions: he was politically involved in Sarkozy’s party (UMP); he and his research teams earned more than 200.000 euros in the 3 years before his nomination.  (See this post on PharmaCritique.)

Philippe Lamoureux, the former head of INPES (National Institute for Prevention and Health Education) went over to the LEEM (French PhRMA), without any “cooling off” period. (See this post on PharmCritique.)

The revolving doors turn very easily in France, as well as in Europe. ALTER-EU (Alliance for Lobbying Transparency and Ethics Regulation) reported about EMA’s former director, Thomas Löngrenn, who took a job as a lobbyist for the pharmaceutical industry, just like other European commissioners. And Guido Rasi, the next EMA director, said at a colloquium in Bologna that an expert without conflicts of interest is not interesting, because drug companies only work with the best…

Some other points in brief:

- there’s no Sunshine Act or any similar obligation in France;

- the 2002 law requiring a disclosure for health professionals talking publicly about a drug is not applied;

- no whistleblower protection (so that libel law is used all the time against them in SLAPP’s: strategic lawsuits against public participation);

- there are no specific laws (like the US False Claims Act or RICO) allowing trials for defective drugs or other abuses; no possibility for a qui tam lawsuit;

- no law to prosecute corruption and its consequences (like the US Federal Anti Kickback Statute);

- no law enabling class actions;

- no specific qualifications for victims of defective drugs (“injury”, “aggravated deception” are those used by Médiator victims and their families…);

- taxpayers pay for the victims (if ever they can get recognition and damages);

- no physician liability for prescriptions and their consequences, or for conflicts of interest and corruption;

- no FOIA; a minimalist law called CADA (« accès aux documents administratifs ») preserves secrecy of data and of conflicts of interests in the name of industrial property and private life protection);

- no corporate integrity agreement;

- no attorney general asset redistribution programs (well, without trials, there’s no need for such frameworks…);

- no disclosure in scientific publications.

Direct-to-consumer advertising is prohibited by law. A good point. But this prohibition is by-passed all the time. Pharmaceutical firms sponsor “health education campaigns” organised together with public institutions, medical societies and/or patient associations tied to drugmakers. For example, a public campaign whose official goal is to raise awareness about the “dangers” of cholesterol is meant to transform a risk factor in a disease, medicalise more and more people who will look for the statins commercialised by the sponsor Pfizer. Not to speak about the repeated attempts of the European Commission to impose the “pharmaceutical package” wanted by EFPIA (European Federation of Pharmaceutical Industry Associations), i.e. enable drugmakers to have a direct access to patients and provide “information”, and weaken pharmacovigilance through several regulations exposed in this text by Prescrire International.

Worst of both socialised medicine and market logic

The French system allies the worst side of socialised medicine and of the market and competition-based system.

Co-payments were introduced a few years ago, but cost reimbursement is still good. Everyone has a public insurance (“régime général”) that covers about 65% of the costs, for a quite large list of drugs and procedures. For the remaining 35%, each individual has to pay for a private insurance. There is a public “universal” insurance for people earning less than 650 euros a month. Nevertheless, about 23% give up health care, because of the costs, and especially because of excessive charges exceeding the statutory fees. This rate is much higher in dental and optical care, where public coverage is almost inexistent.

So what’s the problem, compared with countries without universal health insurance? The problem is lack of organisation, poor economic efficiency and quality, in regard of the high costs. Primary care isn’t organised as it should be in a socialised system. Most of it consists of self-employed physicians working alone, and the same applies for self-employed specialists outside hospitals. They work without coordination and oversight. More and more for-profit hospitals are founded, to treat lucrative, acute diseases, leaving the chronic ones and all complications to public hospitals that still do a good job, but are chronically deficient, because of inappropriate activity-based payment model and budget distribution, and because of budgetary restrictions as a result of an irrational policy of economic management and accountable cost containment.

This lack of organisation originates in organised medicine’s resistance to any restriction and oversight. It hinders every evaluation in terms of quality and leads to specific forms of conflicts of interest and global poor quality. The recent introduction of some pay-for-performance measures worsens the problem; incentives are paid by the social security for objectives that aren’t subjected to any evaluation. Family physicians get up to 9.000 euros extra a year if they obtain the wanted percentages of regular breast screening, influenza vaccines in elderly, and so on. It’s not prevention, but overmedicalisation and aggressive preventive medicine as described by David Sackett.

Organised medicine dominates and shapes France’s medical economy and health care organisation. It also blocks the development of not-for-profit hospitals, created by mutual insurers, as well as any form of medical centres employing physicians. Every attempt to regulate charges exceeding the statutory fees is blocked.

The Order of Physicians is the only “judge” in cases of misconduct, and it rarely forwards the proof to the public watchdogs or to prosecutors. Self-regulation through voluntary codes of conduct is the rule, for the medical corporation as well as for the pharmaceutical industry.

This can’t be called “socialised medicine” and contradicts the republican principles originating in the French revolution, fought to put a stop to corporations and their influence on public decision, on politics and on economy.

Medical consumerism and physician financial interests complete themselves, and “socialised medicine” isn’t appropriate anymore to describe the French system. The dangers for public health care and coverage were pointed out in a paper written by the former medical director of social security, Pr. Claude Béraud.  (See this post on PharmaCritique.)

Of course, such a system isn’t affordable in the long term. And this is exactly what ultra-capitalists and right-wing politicians want, in order to demolish socialised medicine and public health care and promote private health maintenance organisations and insurances.

Passivity, no awareness, no criticism

Another consequence of a deformed conception of socialised medicine is patients’ lack of health education, of healthy skepticism, of criticism and of action. Before the Médiator scandal, patients were too confident in what they thought to be state protection on every level : an approved drug was thought to be sure and useful, an opinion leader’s discourse promoting some new drug was thought to express the highest technical standards, and so on. There was no awareness at all about conflicts of interest.

Physicians’ awareness wasn’t much better. For example, Arnold Relman wrote his paper about “The new medical-industrial complex” in 1980. In France, it took 25 years until Jean-Claude Salomon wrote “The medical-financial complex”…

The only resistance comes from a few organisations, such as the independent medical journal Prescrire and the grassroots NGO Fondation Sciences Citoyennes, and from a few personalities such as senator François Autain, Pr. Claude Béraud and a few others, mentioned by Marc Rodwin in his book “Conflicts of Interest and the Future of Medicine. The United States, France, and Japan”.

The Fondation Sciences Citoyennes and the European Alliance for Lobbying Transparency and Ethic Regulation regularly protest and start actions and proposals about revolving doors, lobbying, conflicts of interests and corruption in all areas, as well as law proposals about expertise deontology and whistleblower protection.

Lots of reports without consequences

The left-wing representatives in the two parliament chambers have put in place hearings about the Mediator scandal, but no enquiry that could enable them to investigate the structural causes of repeated drug and conflicts of interest problems and take concrete measures. Some of the representatives are members of the “Club Hippocrate”, sponsored by Glaxo Smith Kline…

The congressman Bernard Debré and the former medicine professor Philippe Even, known for his longstanding criticism, have written a vehement report about the drug evaluation system. Without consequences. The Inspector General for Social Affairs (IGAS) has published a report on Médiator that clearly points out the responsibilities: every single institution has failed, from the drug agency to the political instances and the medical organisations. The last report of the same IGAS, published in June, contains concrete and pragmatic proposals on how to deeply reform the entire pharmacovigilance and drug evaluation system.

The assessment process initiated by the health minister Xavier Bertrand – Assises du Médicament – has nothing to do with a trial assessing facts (“assises” means a trial with jurors). The working groups were clearly dominated by LEEM (the French PhRMA) representatives and by opinion leaders tied to drugmakers. Most of the independent organisations and critiques were not allowed to participate, “in order to respect a balance” between different interests. Fondation Sciences Citoyennes was excluded and described the situation in this detailed press release, asking independent NGOs to organise counter-Assises. 


The law proposal presented on the 1st August by Xavier Bertrand contains some long due measures, but no real progress.

The pharmaceutical industry’s interests won’t be endangered by any measures and laws arising from the Médiator scandal.

Elena Pasca
Pharmacritique, Fondation Sciences Citoyennes

ADDENDUM - Elena Pasca asked me to insert her thanks that we published her guest post.  But we owe her considerable thanks for her efforts to explain the French situation, and show how the issues we discuss on Health Care Renewal are truly global. 

Guest Blog: Health Care in Dangerous Times

Health Care Renewal presents another guest blog by Steve Lucas, a retired businessman who formerly worked in real estate and construction who has a long standing interest in business ethics, and has long observed the health care scene.

Health Care Renewal has often covered the disconnect between the stated goals of companies and the realities of their day to day operations. This raised the following question: Has medicine moved from being dysfunctional to being dangerous?

There is certainly no lack of material to support this question as in the last two weeks we can find examples of pharma/biotech/device companies all engaged in questionable behavior.

Medtronic and Manipulation of Study Data

In the print media, The Wall Street Journal, a pro-business newspaper regularly highlights stories questioning the actions of companies.

In the June 29 story titled "Medtronic Surgeons Held Back, Study Says" by John Carreyrou and Tom McGinty we find doctors being paid by Medtronic held back information regarding negative out comes of a bone growth product.

'Medtronic paid millions to doctors and those same doctors, oddly enough, published the 'science' Medtronic needed to sell a product,' says Paul Thacker, a former aide to Sen. Charles Grassely…'

Chantix's Cardiac Adverse Effects

In the July 5 story, "Pfizer Drug Tied To Heart Risk" by Thomas M. Burton covers the increased cardiovascular problems with Chantix that only now seemingly have become evident.

However, J. Taylor Hays, a Mayo Clinic doctor who has received funding from Pfizer for research on Chantix, responded in a commentary, 'The risk for serious cardiovascular events is low and is greatly outweighed by the benefits of diminishing the truly 'heartbreaking' of smoking.'

The article then continues:

'Some people have had changes in behavior, hostility, agitation, depressing mood, suicidal thoughts or actions while using Chantix to help them quit smoking,' Pfizer says in safety information.

Overuse of Cardiac Stents

In the July 6 article, "Heart Treatment Overused" by Ron Winslow and John Carreyrou we find the over use of stents and the profit potential for doctors and hospitals.

Outside of heart attacks, doctors are often quick to use a common $20,000 procedure to treat patients suffering from coronary artery disease, a new study suggest.

Untested Imported Drug Ingredients

In the July 6 Op-ed, "Beware the Risk of Generic Drugs" by Roger Bate reinforces a point made often on Health Care Renewal when he covers the importation of untested or tainted product used in our pharmaceuticals.

China is now the largest supplier of pharmaceutical chemicals – hundreds of tons annually – to the world. And pharmaceutical companies that buy these chemicals do not test them.

Moving on to widely read blogs,

Ghost Writing and Risperdal

1BoringOldMan in his post on bipolar kids and the doctors involved in the Harvard debacle discussed an article favorable to the drug ostensibly written by Harvard Professor Josephy Biederman:

This covers the reworking of a previously done study to promote the use of drugs in children with this printed at the bottom of the first page:

“"Printed in the USA. Reproduction in whole or part is not permitted. Copyright © 2006 Excerpta Medica, Inc."

1BoringOldMan continues with this post that since we have identified children as bipolar we are free to ignore other factors and simply medicate them to death.

As reported by '60 Minutes' in September of last year, Rebecca Riley died on December 13, 2006, at her home in Hull, Massachusetts, due to an overdose of psychiatric drugs. The drugs — Depakote (divalproex; Abbott), Seroquel (quetiapine; AstraZeneca), and clonazepam — were prescribed by Tufts psychiatrist Kayoko Kifuji for the child’s bipolar disorder, which was diagnosed at the age of 2 years.

This covers the death of a child, a child, using the above ghost written drug information.

Bayer's Use of Social Media to Market Drugs

Pharma does adjust to the times and market, if it is not explicitly forbidden then it is fair game.

Per a post in Pharmalot entitled, "To Tweet or not to Tweet"

'To Tweet or not to Tweet?' That is a question that Bayer Healthcare will be pondering for some time. The drugmaker was upbraided by the UK’s Prescription Medicines Code of Practice Authority for recently Tweeting about two medicines, which was deemed to be a cause for concern since the information went directly to the public.

Much like shooting a gun into a crowd and then claiming they had no way of knowing they would injure someone, a tweet is sent with the full knowledge the first thing everybody will do is hit the forward to all button.

Pharma's Public Relations People Infiltrate Patient Support Groups

Per a post on the HealthReviewNews Blog we have one of the most frightening posts possible since it shows pharma following individuals and a willingness to intrude into their personal lives.

Marilyn Mann is approached on her Facebook page set up to support parents of children with lipid disorders by a drug PR person to promote a drug.

Hi Marilyn,

A few months ago, I had emailed you about some research I was doing about a new treatment for FH. I am now working with a pharmaceutical company, and the company currently has a drug in development to help treat people with severe FH that may not be responding to current therapies.

In the comment section we find this:

I'm a communications consultant to many big pharma firms and I'm not sure the PR person in this case did anything wrong. She was upfront and polite about her role, and asked if any patients would do what many have done, and be interviewed to raise the profile of FH.
The owner of the group politely declined as was her right.
It would have been a different case if there had been any subterfuge involved, but there wasn't.
I think on this occasion you have aimed at the wrong target.
Good luck with future postings.

What do all of these references have in common? Senior executives, and health care academics, removed from the day to day work of helping people being able to claim they are not responsible while making ever larger incomes.

Natrecor Shown Not to Work

The corporate culture of medicine has become so perverse that even selling a drug that has no benefit becomes acceptable.

Per this item in the Heart Health Center Health Day News:

Study Finds Heart Failure Drug Ineffective

Billions wasted on Natrecor in decade it took to find out it doesn't work, expert says.

By Steven Reinberg, HealthDay News

WEDNESDAY, July 6 (HealthDay News) — The heart failure drug Natrecor (nesiritide) is ineffective and linked to increased rates of potentially dangerous low blood pressure, a new study finds.

Summary: The Most Dangerous Game

So, back to my original question: Has medicine become dysfunctional or dangerous? I would contend dangerous. There is nothing magical about the above listed articles or posts. I am not a professional medical person, nor an academic, only someone concerned by the continued decline of medicine and medical care due to a corporate culture that promotes profit above all else.

When I meet doctors socially they all speak of being small businessmen. Time and time again we see hospital administrators of all types speaking about being the CEO’s of multi-billion dollar organizations.

Drug companies speak of blockbuster drugs as being those with sales of over one billion dollars and fines become the cost of doing business.

Today we have a small, but vocal group of people who feel all drugs should be offered to the public and it is up to them to decide if they are appropriate. They also want the government and insurance companies to pay for this return to the pre-FDA days.

How will the FDA itself withstand the onslaught of new technologies given out current Federal budget concerns? Tweets and Facebook represent only the beginning of a whole new wave of ways to communicate.

My personal opinion is this is a very dangerous time for doctors and patients. Doctors are being pushed into corporate practices where financial gain is the main driver, not health care. Information given to doctors can be so tainted by commercial interest as to be of no value.

Patients have no way of knowing where the doctor’s loyalty lies, with them or the practice? DTC ads are full of half truths and fear mongering. Patients need to bring even more information and skepticism to the doctor/patient relationship.

I fear we do live in dangerous times. The word “good” has left much of medicine.

Steven Lucas MBA