Monday, March 31, 2008

MRK and SGP: Ye shall know the truth, and the truth shall send thy stock spiralling

Apparently, the editors of the NEJM read my blog (even though they stop short of calling for a BOYCOTT):

" seems prudent to encourage patients whose LDL cholesterol levels remain elevated despite treatment with an optimal dose of a statin to redouble their efforts at dietary control and regular exercise. Niacin, fibrates, and resins should be considered when diet, exercise, and a statin have failed to achieve the target, with ezetimibe reserved for patients who cannot tolerate these agents."

Sound familiar?

The full editorial can be seen here:
along with a number of other early-release articles on the subject.

The ENHANCE data are also published online (
and there's really nothing new to report. We have known the results for several months now. What is new is doctors' nascent realization that they have been misled and bamboozled by the drug reps, Big Pharma, and their own long-standing, almost religious faith in surrogate endpoints (see post below). It's like you have to go through the stages of grief (Kubler-Ross) before you give up on your long-cherished notions of reality (denial, anger, bargaining, then, finally, acceptance). Amazingly, the ACC, whose statement just months ago appeared to be intended to allay patients' and doctors' concerns about Zetia, has done a apparent 180 on the drug: "Go back to Statins" is now their sanctimonious advice:

I was briefly at the ACC meeting yesterday (although I did not pay the $900 fee to attend the sessions). The Big Pharma marketing presence was nauseating. A Lipitor-emblazoned bag was given to each attendee. A Lipitor laynard was used to hold your $900 ID badge. Busses throughout the city were emblazoned with Vytorin and Lipitor advertisements among others. Banners covered numerous floors of the facades of city buildings. The "exhibition hall," a veritable orgy of marketing madness, was jam-packed with the most aesthetically pleasing and best-dressed salespersons with their catchy displays and gimmicks. (Did you know that abnormal "vascular reactivity" is a heretofore unknown "risk factor"? And that with a little $20,000 device that they can sell you (which you can probably bill for), you can detect said abnormal vascular reactivity.) The distinction between science, reality, and marketing is blurred imperceptibly if it exists at all. Physicians from all over the world greedily scramble for free pens, bags, and umbrellas (as if they cannot afford such trinkets on their own - or was it the $900 entrance fee that squeezed their pocketbooks?) They can be seen throughout the convention center with armloads of Big Pharma propaganda packages: flashlights, laser pointers, free orange juice and the like.

I just wonder: How much money does the ACC receive from these companies (for this Big Pharma Bonanza and for other "activities")? If my guess is in the right ballpark, I don't have to wonder why the ACC hedged in its statement when the ENHANCE data were released in January. I think I might have an idea.


  1. Perhaps those living in glass houses should have a disclosure on their blog of the cold hard cash they have received as members of an industry speakers' bureau? Shame, shame, shame.

  2. My colleague rightly points out, as I stated in the first post on this blog, that I receive speaker fees from Eli Lilly in relation to their promotion of drotrecogin-alfa, a product that I staunchly support and supported long before receiving such fees, and a product for which there is no competition and which is underutilized. These characteristics are in stark contrast to most industry promotional activities.

    Those issues notwithstanding, I recognize that any man can find convenient rationalizations for his own behavior while all the while disparaging the rationalizations of others.

    So I will leave it to the readers to decide if they would like to dismiss the facts and their possible interpretations as I have stated them, because of my own (perhaps sanctimonious) ties to the industry, the same ties that Danny Carlat described in his self-critical expose in the NYT (which can be found linked to this blog).

  3. This interesting link (with its own set of interesting links) was just pointed out to me:

  4. check this out:

    Especially click on the PDF of the actual e-mail exchanges between the PI and SGP.

    Thanks to Marilyn Mann for pointing this (and other interesting links) out to me.

  5. Another good link, this one to the full transcript from the ACC panel from which the headline quote "back to statins" was taken:

  6. JMO + Aberegg, You two need to kiss and make up.

    Aberegg stated "...So I will leave it to the readers to decide if they would like to dismiss the facts and their possible interpretations as I have stated them..." I think you're biased, it's your blog.
    A view remains a view as long as it is what you choose to believe, but once you want to make a claim of efficacy, it is no longer simply a "view". Anyone can of course hold any view he or she desires, but once it becomes a 'claim', and when someone tries to convince other people of claims of efficacy, proof becomes relevant, one would assume, without bias. Facts can also be distorted and misreported, especially if one has a certain agenda or personality.
    Also, why are you comparing yourself to Dan Carlat? Clearly you see yourself as others do not.

    JMO, you are my sunshine.

  7. From

    A Failed Attempt to Improve Misperceived Greatness: The ENHANCE Trial

    While it seems that sponsors of clinical trials usually end up with results that clearly favor their meds studied in their trial, there are rare exceptions, and Merck and Schering proved that with their disappointing ENHANCE Trial, which many have heard about through the media not long ago. The drug studied was Vytorin, comparing it with Zocor.

    Vytorin is a combination med for high cholesterol and contains Merck’s Zocor, which is now generic, and Schering’s Zetia, which works differently than Zocor, which is one of many statin drugs. Both Vytorin and Zetia are co-promoted by Merck and Schering. So, several years ago, an outcomes study was initiated to prove superiority of Vytorin over Zocor as monotherapy. The trial was named the ENHANCE trial.
    After several years passed, a disappointment arrived for the sponsors of this trial, which was first brought to the attention of Schering in March of 2007, yet the results existed since the spring of 2006, I believe.

    The disappointment is that Vytorin lacked anticipated benefit or superiority over Zocor. Since about 1 million scripts were written for both Vytorin and Zetia every week in 2007, combined with what I believe was about 5 billion in revenue for these two drugs that year, this was a problem for the drug makers. Perhaps for Schering in particular, it was more of a calamity, since over half of their profits and earnings were from these two drugs.
    Being the responsible corporations both companies are, of course, alterations occurred after such events that fractured numerous rules and regulations with clinical trials.

    The trial sponsors delayed the release of the trial results for secrecy reasons, it has been speculated. Results from the trial existed, yet were not disclosed at the time of their discovery. After several months of possessing these trial results that were only known to the manufacturers, they created or implemented some atrocious tactics to improve the trial’s unimpressive results. At the end of 2007, the companies changed the primary endpoint of the trial, which is what the results were measured upon during the entire course of the trial. Since their deliberate concealment of these trial results was clearly wrong, to respond to those who asked where the results were actually while such trial manipulation was occurring and results were being kept secret, Schering stated that continued data analysis from the trial results was the etiology for the delay.

    With clinical trials, case report forms are used to record data from the trials, and are created in a manner where further analysis is not normally necessary, as such forms are quite clear and often not subject to interpretation. So at the end of 2007, both Merck and Schering got the attention of relevant government officials who contacted both companies regarding this ENHANCE trial, and an investigation began into the activities of both companies regarding this trial at that point.

    This became a catalyst for the ENHANCE trial results to be finally released at the beginning of 2008, which caught the attention of major media organizations. In the spring of 2008, a very large cardiology meeting was held, where the audience was told to stick with statins due to this trial’s lack of outcomes for Vytorin, when the ENHANCE trial was discussed at this meeting. Furthermore, a cardiologist at this meeting also suggested that a moratorium should occur with the utilization of Vytorin, since statins are much less expensive, and are highly regarded, as they have been available for a couple of decades. Of course and as expected, Merck and Schering were not pleased, nor were they surprised at the review of Vytorin at this particular meeting. The following month after this cardiology meeting, Schering’s earnings dropped by 48 percent, as I recall.

    Now, these cholesterol drugs promoted by Merck and Schering, Zetia and Vytorin, were aggressively marketed in a number of ways, including investing I believe about 200million dollars in 2007 for DTC ads for these products. To add to this, and soon after both meds were launched, reps from both companies made inferences to doctors about outcomes regarding plaque accumulation and how Vytorin was superior in that area, which, of course, this ENHANCE trial proved it is in fact not the case whatsoever. It did not matter, apparently, to both Merck and Schering that such a claim is entirely void of proof, which Is not unique to any pharma rep, in my opinion. Yet what is known now is that these companies performed junk science with their deliberate manipulation of this ENHANCE trial. Last year, Zetia and Vytorin had about 20 percent of the cholesterol lowering market. It does not seem that there will be an increase of this percentage because of this scandal.
    Worst of all is the harm caused to both doctors and patients. The ENHANCE trial concerned and confused both of these participants in the health care system. Furthermore, it’s likely they were devastated by being so clearly misled by the marketing of both Merck and Schering regarding the false benefits of Vytorin they were led to believe by the companies that promoted them.
    This whole situation is another example of the corruption of the scientific method by placing profits over the well-being of patients. Most were shocked by Merck behaving in such a way in particular because of what use to be their excellent reputation as an ethical pharmaceutical company. And this alone shows the progression and infiltration of such damaging corruption that desperately needs to be stopped and corrected for the sake of others.

    Don’t just say something. Have something to say- to the right people, with conviction and with others who share your views.

    “Waste no more time arguing what a good man should be. Be one.” --- Marcus Aurelius

    Dan Abshear