Wednesday, December 24, 2008

The Great Brain Robbery


In a recent blog post on Psychology Today, Nassir Ghaemi MD of Tufts University frankly discusses the "steroid problem of academia."

This concerns ghost authorship. What happens is common practice in journal publishing, especially in psychiatry. A drug company will design and write its own study, complete with its own spin favoring the drug in the study. Then the company invites respected academic researchers to front the study as authors. The study then appears in a medical or psychiatric journal. (For more detail how this works, check out my website article.)

What's in it for the "authors" is fame and academic distinction. In a university publish or perish environment, there is intense pressure on academics to rack up credits any way they can. The problem, says Dr Ghaemi, is that "some of our experts get their fame artificially, their achievements appearing greater than they really are."

In his blog, Dr Ghaemi reports how a department head actually encouraged him to engage in this type of fraud (he refused). Dr Ghaemi also reports how, fairly recently, a past president of the American Psychiatric Association and another luminary expressed complete surprise to him that this type of thing was going on. (This ignorance is astounding in light of the fact that eight or nine years ago, about a dozen journals worldwide ran simultaneous editorials highlighting the situation and promising corrective action in their own publications.)

Dr Ghaemi has devoted much of his professional life to researching the use of antidepressants in treating bipolar depression. His research has been influential in convincing psychiatrists to think twice before prescribing. His data shows that not only is the benefit problematic in a bipolar population, but there is risk of switching patients into mania and rapid cycling.

Not surprisingly, you will not find drug companies stampeding to fund studies to prove Dr Ghaemi right.

How serious is the problem? Early in 2008, in preparing for a grand rounds lecture I was to deliver to a psychiatric hospital in Princeton, I came across a 2006 study published in the American Journal of Psychiatry, which is put out by the American Psychiatric Association. The study concerned bipolar patients on Zyprexa, and was designed and written by Eli Lilly, which manufactures the drug.

The article listed Mauricio Tohen MD, DrPH as the lead author of the study. In all likelihood, Dr Tohen most likely did have a major hand designing and writing the study. A PubMed search of "Tohen M, olanzapine" reveals 92 published articles he authored between 1998 and 2008.

Dr Tohen is virtually unique in psychiatry in that he is affiliated with Harvard and Mass General Hospital AND is employed by Eli Lilly. In addition to Dr Tohen, the article listed eight other authors. Three of the names were instantly recognizable as prominent academic thought leaders.

According to the abstract of the study:

"Compared to placebo, olanzapine delays relapse into subsequent mood episodes in bipolar I disorder patients who responded to open-label acute treatment with olanzapine for a manic or mixed episode."

But the study data, not mentioned in the abstract, told a far different story. In fact, eighty percent of the patients in the study stopped taking their Zyprexa.

When I raised this to my audience of clinicians in my talk, I asked if anyone thought this was deceitful. All hands went up. I would go further, I said. I would say it's immoral.

Zyprexa is an antipsychotic with a high side effects profile, and it's not surprising that four in five bipolar patients choose not to take it, even if they are otherwise doing well on it. As Holly Swartz MD of the University of Pittsburgh told a symposium at the 2006 APA annual meeting: "If a patient doesn’t stay on it, it doesn’t do any good, even if it works.”

No doubt, I ranted and raved far too much in my talk, but as a patient I represent the greatest stakeholders in this debate. Am I going to end up in crisis - or worse - as a result of a well-meaning doctor sending me out the door with the wrong prescription based on deliberate misinformation?

Does anyone see a blatant violation of the "do no harm" principle at work?

I have no objection to productive partnerships between industry and academia. Indeed, drug companies would be incredibility stupid not to tap into this invaluable brain trust. Likewise, academics deserve to profit handsomely from any research that improves our chances of leading productive and rewarding lives.

What I object to is drug companies debasing psychiatry by employing its best and brightest as errand boys. Meanwhile, far too many highly-dedicated researchers are forced to leave the field due to lack of funding. We are left struggling in the dark. Our doctors get treated to infomercials.

4 comments:

Discover What You Think said...

Atypical Psychotics


Not long ago, I got the joy and despair of viewing many documents that were initially not to be seen, by order of the Department of Justice, yet found their way on various locations on the internet- specifically, the website: www.furiousseasons.com. The documents are, or were, in fact, evidence against Eli Lilly entirely representing their decade of deception promoting and over-medicating others with their drug called Zyprexa, which is in a class of medications called atypical anti-psychotics. While a new a new molecular entity by definition, this new class called atypical antipsychotics in fact is chemically similar to the older and typical anti-psychotics that exist, such as Haldol. In many ways, the older antipsychotics are safer as well as being similar in efficacy compared with the atypicals such as Zyprexa. Perhaps this is why Eli Lilly did the things they did because they knew Zyprexa caused perhaps more harm than good for those who took the medication. Of the several available atypical anti-psychotics now available, Zyprexa and Clozaril, which was the first atypical anti-psychotic, are believed to have the most toxic adverse events to those who take these two in particular.

Launched in 1996, Eli Lilly did not appear to consider any adverse effects that may occur to those who take this drug, yet it is believed that there was reason to believe that there should be caution regarding its use. With the belief that the maker of Zyprexa is and will be exonerated from any responsibility related to Zyprexa, many surmise that Eli Lilly was pleased that others were taking Zyprexa , and was confident that they would be exonerated from any responsibility from the adverse effects of the drug.

At the time Zyprexa was granted approval for marketing, the medication was indicated only for schizophrenia and mania that exists in those with bipolar disorder. Schizophrenia has been defined as a disease that causes the sufferer to deviate from true reality, along with visual and auditory hallucinations. Bipolar disorder is another mental disorder where the victim alternates from states of heightened neurokinetics to periods of what can be brutal depression for the sufferer.

Eli Lilly, known in recent years for their focus on marketing over science or research, greatly desired and hoped that Zyprexa would be a welcome blockbuster, which is a medication that exceeds a billion dollars a year in sales as a minimum. Likely because of this state of greed of Eli Lilly, they did not consider or evaluate any possible damage this flagship drug may cause others. And Eli Lilly appeared to have the obedient and manipulated sales force presumed to be a necessity for this monetary goal to occur without interference.

Pharmaceutical representatives overall are attractive and young individuals with little if any medical knowledge or training, but are determined to have charming personalities along with a perception of obedience, and this is all Eli Lilly in particular wanted from the members of their sales force. The sales vocation is normally associated to contain members with a high affinity for money, so corruptive acts such as off label promotion or overt kickbacks is not typically a consideration of such people, overall, as history has shown. Therefore, if Eli Lilly’s sales representatives who happen to be instructed to sell Zyprexa for dementia or depression, the orders will likely be followed. Or if this sales force is instructed to pay specifically targeted doctors large amounts of money for doing little or no work for this money given to such doctors, it still is not a problem for the sales force to maintain their obedience to their corporate God.

A few years after Eli Lilly launched Zyprexa, they appeared anxious due to their obvious disappointment regarding the initial prediction that was speculated about the growth of this drug that was not meeting their expectations, so they had meetings throughout the nation, known as ‘plan of action’ meetings, and concluded afterwards that there is great benefit from a monetary paradigm of implementing ‘seeding trials’, as they are a mechanism for generating needed, although fabricated data void of any scientific gain of knowledge. This amazingly was done and implemented afterwards rather overtly. Even more unbelievable is that around this time, the Zyprexa sales force was instructed by Eli Lilly management to seek out clinical trial sites, along with investigators for these trials. One voiced stipulation was that the investigators had to either be Eli Lilly prescribing supporters or high volume prescribers. This protocol described was written internally, along with the etiology for performing these sham clinical trials. Anything in writing can be golden, from an illegal situation such as this.

In addition to the clinical trial plan of action, Eli Lilly instructed its sales force to utilize inaccurate promotional material that Eli Lilly gave its Zyprexa reps without exception, even though this material was false and misleading, which was the intent of Eli Lilly, according to others, along with this material being greatly unbalanced and suggested uses for Zyprexa that were not indicated if not unproven, which can and has been harmful to patients because of this. To further saturate and corrupt the Zyprexa sales force, they were coerced to blunt assertively what are at this time widely recognized adverse effects of this medication, such as massive weight gain, along with glucose and lipid abnormalities- all of which are dangerous to the user of this medication.

The corrosive promotion of Zyprexa by Eli Lilly continued as the dangerous company intentionally altered certain Zyprexa articles by rewriting them, followed by being reviewed internally after this art work. The purpose was to stimulate what Eli Lilly believed was clearly absent, which was much needed commercial interest related to Zyprexa.

Then it came time to essentially buy benign support groups in hopes that this would improve the growth of Zyprexa. One example is that Eli Lilly paid the American Diabetes Association for their assistance in obtaining endocrinologist consultants, which is a medical specialty that treats, among other things, diabetes. To reduce any possibility of an unexpected contingency doing this, they went ahead and hired a good sized team of diabetes educators. In 1999, Eli Lilly altered a Zyprexa report that originally illustrated the glucose problem with the medication, and did so with deliberate intent and reckless disregard for others. Eventually, the American Diabetes Association became quite the critic of Eli Lilly because of their harmful behavior regarding Zyprexa.

Amazing alliances between Eli Lilly and the Bush administration have existed as well. George H.W. Bush became an Eli Lilly director after leaving the CIA and lobbied to infect third world countries with Lilly medications. He also did his best to maximize tax breaks further for this industry that now employs both himself and his political affiliation. In fact, many members of this administration have some connection with Eli Lilly. It seems to be a revolving door issue once again. One could speculate that the Zyprexa campaign continued for so long because of the relationships the maker of the drug had and has with other powerful people.

The next psychotic tactic Eli Lilly created was an advisory board paid well by this company to focus on the progressing concerns of Zyprexa. This tactic did work briefly, but did not change the view of the drug by the medical community in any way, or the maker of this drug.

It is at this point that the medical community began to get vexed and irritated by Eli Lilly’s deceptive and overtly destructive tactics, which included the company’s own speakers that were utilized in the past. This event of Eli Lilly being ostracized was because of their disregard for those they are obligated to serve in the medical community. Perhaps most disturbing was the company’s intentional holding of crucial safety information related to Zyprexa even before the drug was even approved. For example, Eli Lilly’s Zyprexa representatives were instructed without doubt to neutralize the legitimate concerns doctors may have about Zyprexa, if not outright fear regarding this deadly drug they now perceived as being a clear reality. The representatives were in agreement of continuing to dodge or neutralize legitimate concerns about Zyprexa, with the promise of Eli Lilly’s management team to fill their wallets more if they maintain obedience regarding this directive that caused harm in the form of such physiological disorders as metabolic syndrome associated with Zyprexa, yet the sales force still denied the association due to the insistence of their employer. Essentially, the Zyprexa representatives with Eli Lilly were trained, perhaps aggressively, to disarm negative perceptions about Zyprexa, even though these perceptions continuously proved to be valid. This deeply troubled many Zyprexa representatives, as at this point they were aware of the dangers of the drug they were promoting in order to maintain employment.

Also, and of no great surprise, off label promotion with Zyprexa was a norm within the organization and certainly encouraged by Eli Lilly management. Encouraging doctors to prescribe Zyprexa for depression is one example. Amazingly, reflecting back on the behavioral flaws by Eli Lilly for quite some time, they did not alter their method of business even though there was a strong perception regarding this company being both aggressive and greedy, and likely criminal in the way they chose to conduct their business. And depression was not the only off label claim with Zyprexa. Eli Lilly considered such criminal acts as off label promotion as ‘redefining the market’. This is yet another example of their absurdity.

In the year 2000, Eli Lilly greatly expanded what was called their long term care sales force to expand Zyprexa intake in the elderly. This, as a reminder, is deadly- as Zyprexa is harmful to older citizens- specifically pneumonia and eventual premature death result from Zyprexa intake. At the same time, Eli Lilly developed a strategy to neutralize the obvious weight gain associated with Zyprexa with other patient populations. Does the whole corporation believe U.S. citizens are without thought or intelligence?
Yet in 2002, Eli Lilly was having financial disappointments, which again did not shock many. So to stay in form, they went on a mission to develop speakers to align with them and to not educate others, but to pacify other doctors in hopes that their problems with Zyprexa would disappear. After the speaker episode, Eli Lilly had the audacity to claim that Zyprexa was indeed the best in the class of atypical antipsychotics. Such a statement appears psychotic, to say the least. And now the market for atypicals is about 5 billion a year, so there seemed to be no end as to what Eli Lilly might try next. Also in this year our FDA called Eli Lilly ‘a sponsor’. I find that a bit disturbing. As disturbing as the covert meetings Eli Lilly had with the FDA as well. Well, if you are going to have a friend,that is the right one. Eli Lilly also bribed select reporters to speak or annotate favorably about Zyprexa, and they did.

As the new millennium progressed over a few years, lawsuits became a concern for Eli Lilly regarding Zyprexa. Doing what any responsible corporate entity would most certainly do, the upper management of Eli Lilly had the audacity to blame the media for the way they handled their patients. Around this time, Eli Lilly needed and did hire a public relations firm because of their image crisis. About the same time, Eli Lilly implemented a nationwide program entitled, “Operation: restore confidence”. I’m not sure how a fully rational and conscious group of Eli Lilly people could create something so ridiculous and unrealistic. Equally deviating from reality of Eli Lilly’s behavior is that they actually thought they could increase Zyprexa growth by hammering home astronomical efficacy with the drug which, of course, does not outweigh the damage of the drug to the patient who takes it.

Another failure illustrated above caused Eli Lilly to hire a group called Lifeplan Marketing, who convinced the organization to create a brand new market establishing Zyprexa as the standard of care. This is yet another psychotic act by this Midwest group of manipulators, who were at one time a well respected pharmaceutical corporation. Humans do not forget- especially pain.

At least one human wanted to let everyone know he did not, nor will he ever forget his experience as a Zyprexa representative with Eli Lilly. His name is Shahram Ahari and he aligned with a non-profit advocacy group called Pharmedout, which was created due to a state settlement from another pharmaceutical company. He spends his days now making others aware of things such as what you have read. I’ve spoken with Shahram, and I admire his assistance with others trying to correct this medical mess.

Eli Lilly appears pathologically persistent in frightening ways. Next was a national implementation plan of action which focused on training the Zyprexa sales force to use what was called a J.C.P. study to emphasize the numerous off label benefits of Zyprexa. At the same time, Eli Lilly determined that primary care doctors should be their number one Zyprexa targets. With this new focus, the sales force for Zyprexa were somehow convinced to tell doctors that fatigue is really the only side effect that presents itself with Zyprexa use. Again, citizens are overall not catatonic about such actions.

While on this off label role with Zyprexa, they resurrected their long term care efforts by taking on Aricept, and Alzheimer’s drug, and encouraged others to switch to Zyprexa. The reaction for this misbehavior was Zyprexa being removed from Medicaid in 2004.
Allan Reier was the Zyprexa product team leader at the time. He may have developed the unbelievable strategy of visiting psychiatrists to assure them they will not be sued if they prescribe Zyprexa for their patients.

So, now we are at a point where Eli Lilly had a flash of reality and preferred no media contact. Gosh, what a surprise. There was also the disclosure of Eli Lilly creating if not funding deceptive front groups to screen others in order to sell more Zyprexa as well.

The other tactical plan from Eli Lilly was to re-implement blunting techniques regarding Zyprexa. My guess is that they dragged this into a week- long meeting. This of course included dodging concerns by doctors that they are normally encouraged to partner with, historically. Such tactical plans of action were associated with such clever names as, ‘Viva Zyprexa’, or Zyprexa Limitless”. Maybe the next one will be ‘Zyprexa Revenue Regression’.

Another tactic authorized by Eli Lilly was to use those bonafide contract research organizations (CROs) to manufacture safety, health, and outcomes database studies. A deceptive publication plan followed. CROs are commercial research organizations that include substandard research investigators and the sponsor of these clinical trials, Eli Lilly, has the ability to alter aspects of such trials for their own benefit. This was done as they still encouraged children to consume Zyprexa- near a million of them due to an arrangement that Zyprexa will be promoted by the ADD drug Strattera.
As stated earlier, previously sealed and damaging documents got exposed at the end of 2006, and are accessible on the internet and some websites, such as www.furiousseasons.com, which is what this article is based upon entirely.

Perhaps the documents should have been exposed immediately instead of being held from public view. Many facts that you have read in this article are from these authentic documents that are more disturbing than fiction. The information is accurate, and many others are finally informed instead of deceived or denied their right to know.

Eli Lilly makes over 4 billion dollars a year on Zyprexa.
Eli Lilly has had to pay well over a billion dollars for Zyprexa damage to others between 2006 and 2007.
Eli Lilly raised the price in Europe of Zyprexa by nearly 20 percent afterwards.

“Character is what a man is in the dark” --- Dwight Moody

Dan Abshear

Author’s note: What has been written is based upon information and belief..

John McManamy said...

Hi, Dan. Many thanks for an informative and thoughtful piece. In my Newsletter, I reported on the diabetes risks of Zyprexa when the studies first came out back in 2003, plus studies that showed atypicals were no better in efficacy to the 1st generation neuroleptics long before CATIE. I also reported on Shahram Ahari's eye-opening PLoS article.

So the point: I expect corporations to act in their best commercial interests, often at the expense of our interests, and often unethically.
I don't approve, but it's a fact of life.

What I cannot countenance is doctors who forget they are supposed to be acting in OUR interests. They are supposed to be our first line of defense against corporate oversell, but too often turn out to be their accomplices.

Mind you, there are good medical reasons for using Zyprexa, and I have personal knowledge of people who have a new lease on life thanks to the med. But this is the difference between smart medicine and dumb medicine. Way too much dumb medicine is being practiced, and our only protection is smart patients. The name of this blog isn't called "Knowledge is Necessity" for nothing.

Anyway, many many thanks for your post. Please keep posting.

Anonymous said...

I read somewhere that average weight gain for people on Zyprexa over several years was... 100 pounds. I know at least one person who takes it and gained more than that. Bulletin boards are also awash with people experiencing dramatic weight gain, which is no doubt linked with the diabetes. My pdoc put me on it but I have a family history of diabetes and didn't want to continue. Now I take Nozinan, which seems to work quite well. I have gained weight over the past several months but several factors may be at work.

John McManamy said...

Hi, Anonymous. I'm not an MD and I don't want to second-guess your pdoc, but as a general rule: Unless the pdoc can cite an overwhelming clinical reason or unless other options have been exhausted, it should be considered medical malpractice to prescribe Zyprexa to someone with a family history of diabetes or to anyone in a diabetic risk category.

There are medical guidelines saying that physicians should be carefully monitoring weight, glucose levels, etc for patients on Zyprexa. My guess is these guidelines are honored in the breach.