Friday, February 10, 2012

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.

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.

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.


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