Wednesday, August 27, 2008
Be The Power:
2 GI risk (and ZERO cardiovascular risk)
How 'bout a nice dose of data? Oh, this clip is SO rich!
Tuesday, August 26, 2008
Monday, August 25, 2008
Go to vioxxdocuments.com for more such goodies.
Tuesday, August 19, 2008
Leo compares the data on SSRIs and suicide to the blatantly false statements made by the The Infinite Mind commentators. He notes, for example, that it is utter BS to state that nobody committed suicide in antidepressant trials submitted to the FDA -- in children there were no suicides, but among adults there certainly were. And kids who dropped out of the studies due to poor response or side effects, well, who knows what happened to them?
Leo also notes that the commentators were dead wrong about their alleged evidence linking decreased prescriptions of SSRIs to an increase in suicides. I also noted the same problem. He then proceeds to make point after point about the commentators overstating the efficacy of antidepressants.
As I've written before, conflicts of interest are important. But rather than just noting that people have conflicts, it is important to show the data -- are people with conflicts of interest misstating the evidence in a manner that reflects the conflict of interest? In the case of The Infinite Mind, the answer is a clear yes. Leo's post is quite lengthy, but well worth the time.
Update (08-31-08): My mistake. I had earlier called the program All in The Mind, which is vastly incorrect. The program was The Infinite Mind (as has been corrected above). This post has absolutely nothing to do with All in The Mind, which is a program which airs on Australia's Radio National. In fact, I've listened to a couple of All in the Mind broadcasts previously and found them to be well-done. Thanks to a commenter for catching my error.
Lilly was using cases of patients--apparently with bipolar disorder, likely type 2--who ran into problems on SSRIs such as agitation to create a scenario for selling doctors on using Zyprexa in these patients.Snippets from sales call notes are then added to strongly support this assertion. Well worth a read. Especially the clincher that involves the old-fashioned trick of bribing docs with candy to get them to write Zyprexa scripts. If I get a little spare time, I hope to wrangle through the new Zyprexa docs and spread the word about whatever horrors lie therein.
Monday, August 18, 2008
The study, however, was conceived and conducted by Merck’s marketing department. Why? As Vioxx was about to come to market, Merck needed to develop a need for their product. By hiring physicians to participate as “investigators” on this trial, Merck was exposing its product to an important group of potential customers. To quote Merck:
The objectives were to provide product trial among a key physician group to accelerate uptake of VIOXX as the second entrant in a highly competitive new class and gather data important to this customer group. The trial was designed and executed in the spirit of the Merck marketing principles.
Other snippets from a Merck marketing memo, with pithy commentary added free of charge:
- "...the trial was targeted to a select group of critical customers.” So the main qualification to be a “research investigator” in this trial was to be a customer that Merck wanted to win over.
- “The sales force nominated potential investigators and completed intake forms, allowing a very large number of sites to be evaluated and enrolled and ensuring equal distribution of investigators across the business groups.” Again, the sales force chose the physicians, apparently based on how easily they could be swayed to prescribe Vioxx as a result of participating in this study.
- “An analysis performed at 6 months post launch demonstrated a significantly higher level of prescribing for VIOXX among primary care ADVANTAGE investigators compared to a control group of VIOXX 99 prescribers (see attached). Feedback from the field has been overwhelmingly positive about their ability to access key customers and the influence that being involved in the trial has had on their perceptions of VIOXX and Merck.” The program apparently had its desired results – more docs prescribing Vioxx as a result of their participation in Merck marketing-designed “research.” As for the patients dying due to taking Vioxx, well, what’s a little collateral damage when there are quarterly sales goals to be met?
The name for such an exercise in marketing is a “seeding trial,” referring to a company planting seeds in physicians to use their product under the guise of research.
II. What about getting the results out?
According to Merck: “Preparations are now underway for analysis and publication of the data, which will utilize key investigators as authors and advisors.” Turns out that worked pretty well – as the lead author on the main ADVANTAGE publication told the New York Times that “Merck designed the trial, paid for the trial, ran the trial. Merck came to me after the study was completed and said, “We want your help to work on the paper. The initial paper was written at Merck, and then it was sent to me for editing.” – it was sent to him to place a veneer of academic credibility on Merck’s marketing-run trial.
Even Merck’s head of research said that trials such as ADVANTAGE are “intellectually redundant” – as they tend to focus on results that are already well-established, such as showing Vioxx to be somewhat easier on the gastrointestinal tract that naproxen.
Harold Sox and Drummond Rennie, also writing in the Annals of Internal Medicine, in a critique of Vioxx’s marketing wrote:
This practice—a seeding trial—is marketing in the guise of science. The apparent purpose is to test a hypothesis. The true purpose is to get physicians in the habit of prescribing a new drug. Why would a drug company go to the expense and bother of conducting a trial involving hundreds of practitioners— each recruiting a few patients—when a study based at a few large medical centers could accomplish the same scientific purposes much more efficiently? The main point of the seeding trial is not to get high-quality scientific information: It is to change the prescribing habits of large numbers of physicians. A secondary purpose is to transform physicians into advocates for the sponsor’s drug. The company flatters a physician by selecting him because he is “an opinion leader” and incorporates him in the research team with the title of “investigator.” Then, it pays him good money: a consulting fee to advise the company on the drug’s use and another fee for each patient he enrolls. The physician becomes invested in the drug’s future and praises its good features to patients and colleagues. Unwittingly, the physician joins the sponsor’s marketing team. Why do companies pursue this expensive tactic? Because it works.
This is hardly the biggest problem with Vioxx, as its tendency to kill people en masse via heart problems is obviously a far more important issue. And we all know at this point that Merck made sure to underplay the risks of Vioxx, and that the medical community was also asleep at the wheel when it came examining published studies on the risks of Vioxx. Nonetheless, using the guise of science to recruit naive (or greedy) physicians to serve as Vioxx pushers is contemptible.
Merck was out pushing how wonderfully safe and well-tolerated was via a “study” designed solely to turn “investigators” into top Vioxx prescribers, while at the same time, more and more people were meeting an early end due to this purportedly safe new drug.
For more hot Vioxx action, check out this site.
Update (8-19-08): Check out an interview with Dr. Kevin Hill, lead author of the investigation of the ADVANTAGE trial, over at the Carlat Psychiatry Blog. As always, Pharmalot also has a good post on the topic.
Friday, August 01, 2008
From an excellent piece at Bloomberg:
"The doctor's thinking that he does not see a schizophrenic or bipolar patient,'' [Zyprexa brand manager] Bandick said in a December 2000 internal e- mail to the marketing department. "But he probably does see patients with symptoms of behavior, mood and thought disturbances,'' he wrote. "Even if the doctor does not have diagnosis, he should treat anyway.''Adding more fuel to the fire I discussed in February 2007:
The document discussed in this post is called the “Zyprexa Primary Care Presentation”. It appears to be a transcript of a speech Mike Bandick, the Zyprexa Brand Manager, gave at the Eli Lilly National Sales Meeting onBut don't worry -- Lilly will tell you that they don't promote off-label. Do keep in mind that I'm not singling out Lilly, as this kind of thing seems to be par for the course.
March 13, 2001.
It is important to note that Zyprexa is only FDA-approved for use in schizophrenia and bipolar disorder. The document appears to indicate that Bandick was encouraging salespeople to market Zyprexa for treating more than just these two conditions.
We intend, quite simply, to redefine the way PCPs treat mood, thought and behavioral disturbances. We will continue to focus on symptoms and behaviors that PCPs see every day.
Later he said, referencing Zyprexa:Broad symptom efficacy in mood, thought, and behavioral disturbances.It seems curious that Lilly states they did not market Zyprexa for off-label purposes, yet the term “Mood, thought, and behavioral disturbances” seems a fair amount broader than schizophrenia and bipolar disorder. In addition, schizophrenia and bipolar disorder (especially bipolar I, which is the much more severe form of bipolar in comparison to bipolar II) are uncommon disorders. It is highly unlikely that primary care physicians would see patients with such conditions “every day.” However, it is certainly possible that a PCP may run across individuals who are manifesting much less severe “disturbances”, and it may well have been that it was this group, the patients who exhibited mild “mood, thought, or behavioral” symptoms, for whom Zyprexa was being marketed.
As for risks of Zyprexa, well, according to Bloomberg...
The Bloomberg article is a must-read.
Lilly added a warning to its packaging in October 2007 saying that more than half of patients in 13 studies gained an average of 12 pounds after taking the drug for less than a year. It said Zyprexa was more associated with higher blood sugar levels, a risk factor for diabetes, than similar medications.
Before the October 2007 label change, Lilly didn't instruct its sales force to say Zyprexa's diabetes rates were higher, former marketing director David Noesges said in a January deposition.
"We will NOT proactively address the diabetes concern,'' the Zyprexa sales force was advised in 2002, the documents show. "The competition wins if we are distracted into talking about diabetes."