Everyone knows it goes on. Big Pharma either solicits or creates scholarly review articles that paint its drug in a favorable light, attributing the writing entirely to a prominent thought leader in the field.
But this article in today’s New York Times exposes the process in a way none has before, following the production of a review article from it’s first inception in a Wyeth stratgey meeting to the hiring of a ghost writer and the correspondance with the attributed author, its rejection by a peer review journal and final publication in a throw away.
Most of us docs know that the articles in throw aways are slanted towards Big Pharma’s agenda, and if we read them, do so with that in mind. But some of these ghost-written articles make their way into peer-review journals. One could argue that the peer-review process should weed out the artciles that are not medically correct. But what if the peer reviewers have conflicts similar to those of the supposed author?
Oh, what a tangled web we weave…
I’m so pleased that it’s a member of the republican party who’s taking the lead on this. With our new democratically controlled congress, I hope we will see – at least an attempt – at legislation that will take the profit motive out of the pharmacetical industry completely.
Published on http://www.brainblogger.com:
A Failed Attempt to Improve Misperceived Greatness: The ENHANCE Trial
While it seems that pharmaceutical company 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 drugs studied were Vytorin, which was compared 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. The trial was named the ENHANCE trial, and possibly this trial was initiated because Zocor is generic now, and not a priority from a profit paradigm of its creator.
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 upon information and belief.
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, meaning a fear of shareholder reaction. Perhaps for Schering in particular, it was more of a calamity, since over half of their profits and earnings were from these two drugs with Schering, I understand.
Being the responsible corporations both companies are, of course, alterations occurred after such events were discovered that fractured numerous rules and regulations with clinical trials, possibly in illegal and unethical tactics.
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 following the original results of this ENHANCE study. 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. Sort of like sorting cards to make a good hand not dealt to you. Anyway, since their deliberate concealment of these trial results was clearly wrong, to respond to those who asked where the results were actually as they had been anticipated for quite some time, and 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 as implied by the trial sponsors, one could conclude. 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 due to such suspicions on the facts known and presented, 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, as expected. In the spring of 2008, a very large cardiology meeting was held, where the audience was told, I understand, to stick with statins due to this trial’s lack of outcomes for Vytorin, when the ENHANCE trial was discussed at this meeting. Furthermore, it has been said that a cardiologist at this meeting also suggested that a moratorium should occur with the utilization of Vytorin by prescribers, since statins are much less expensive, and are highly regarded, as they have been available for a couple of decades, starting with Mevacor in the 1980s. 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. Also during much of this year, Schering in particular blamed the media for amplifying the situation regarding the ENHANCE trial.
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 claims were is entirely void of proof, which is not unique to any pharma rep, in my opinion. No remorse or regret from the makers of these drug makers, either, which did not shock many. Yet what is known now is that these companies, as stated by other researchers, performed junk science with their deliberate manipulation of this ENHANCE trial using such tactics. Also, 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. Possibly if they presented the truth, the future of these meds might be better than what is anticipated presently.
Worst of all regarding this ENHANCE trial scandal 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- the health care providers in particular.
This whole situation is another example of the progressively frequent discovery of corruption of the scientific method by placing profits over the well-being of patients, which harms the well being of patients. In addition, 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 ethical atrophy that desperately needs to be stopped and corrected for the sake of others- for everyone.
Don’t just say something. Have something to say- to the right people, with conviction and with others who share your views.
“Try not to become a man of success, but rather try to become a man of value.” — Albert Einstein
Dan Abshear
Author’s note: What you have read is based upon information and belief. Thank you
I agree that for these ghost written articles that don’t hold up to peer review that they should be ignored. And while I don’t think that the Senator referenced in the article should legislate around it, if he does, I certainly don’t think that just the big pharma company should be pulled in. There should be EQUAL penalties for the doc who is willing to put his/her name on it -even if they haven’t taken money.
If everyone is so willing to throw the drug companies under the bus, they should do so of their peer as well. Then, if the science is not solid, then individuals should be held accountable along with the pharma company in whatever way the Senator has in mind.
So let’s assume that Wyeth’s claim is correct – that there was no payment of any kind for the authoring of the paper. What then? Is there an equal amount of shame in this? You don’t pose this perspective, just the slam on big pharma again. The same big pharma which brings products you likely use in your practice everyday.
Now, I think that a poor publication is so completely harmful to the company that they are entirely foolish to go forward with it. It just feeds into the reputation many have of the industry that the companies are just snake oil sales people. They should know better and behave better. The standard they hold themselves to should be much higher. If they can do this, then they will be in a much better place to publish alone, and not need a doc to ghost author a paper. No doubt that the aresenal of excellent scientists they have on staff should be sufficient.
As for the post about ENHANCE – what is written is seemingly plausible. The timeline is suspect for sure. However, the facts related to the timeline aren’t out entirely, so I think I will wait until the data is complete. Assuming anything before the data is available is dangerous and judgemental. I wonder if you will get an equally candid opinion if in the end the big-pharma perspective was right afterall…somehow I doubt it. Who on earth would be to blame then? Must be the media then.
Big pharma and physicians need each other. Neither is thriving. Should everyone be working together to improve things?
As long as we’re Pharma bashing, today the Federal Trade Commission filed a lawsuit against the maker of IV indomethacin for buying out the only competing drug in the class so they could keep the price at $500/vial. What makes all of this price gouging worse is that the medication is used to treat a congenital heart defect in babies called Patient Ductus Arteriosus. I post on this at: http://thecountrydocreport.wordpress.com