A Failed Attempt to Improve Perceived Greatness: The ENHANCE Trial

Drugs and Clinical Trials CategoryWhile it seems that sponsors of clinical trials usually end up with results that clearly favor their medicine, there are rare exceptions. Merck and Schering-Plough proved that with their disappointing ENHANCE Trial which many have heard about through the media.

Vytorin is a combination pill for high cholesterol and contains Merck’s Zocor, which is now generic, and Schering’s Zetia, which works differently than Zocor — one of many statin drugs. Both Vytorin and Zetia are co-promoted by Merck and Schering. Several years ago, an outcomes study was initiated to prove superiority of Vytorin over Zocor as a single therapy. The clinical trial was named the ENHANCE Trial.

Medicine bottleAfter several years passed, the trial sponsors faced disappointment which was first brought to the attention of Schering in March of 2007, however, the results existed since the spring of 2006, I believe. The disappointment is that Vytorin lacked anticipated benefit over Zocor. Since about 1 million scripts were written for both Vytorin and Zetia in 2007, combined with what I believe was about $5 billion in revenue for these two drugs, this was a problem — perhaps for Schering in particular, since over half of their profits and earnings were from these drugs.

Being the responsible corporations both companies are, of course, alterations occurred after such events. The trial sponsors delayed the release of the trial results for secrecy reasons, it has been speculated. Although the trial results existed, they were not disclosed at the time of their discovery. After several months of possessing the 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 its course. Since their deliberate concealment was clearly wrong, in response to those who asked if trial manipulation was occurring, Schering stated that continued data analysis from the trial was the etiology for the delay.

With clinical trials, case report forms are used to record data and are created in a manner where further analysis is unnecessary, as such forms are quite clear and 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. An investigation began into the activities of both companies at that point. It became a catalyst for the ENHANCE Trial results to be finally released in 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. Furthermore, a cardiologist at this meeting also suggested that a moratorium occur with the utilization of Vytorin, since statins are much less expensive, and are highly regarded since they have been available for a couple decades already. 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%.

Now, these cholesterol drugs promoted by Merck and Schering, Zetia and Vytorin, were aggressively marketed in a number of ways including investing what I believe to be about $200 million in 2007 for direct-to-consumer ads for these products. To add, and soon after the medications were launched, representatives from both companies made inferences to doctors about outcomes regarding cholesterol-plaque accumulation and how Vytorin was superior in that area, which, of course, this ENHANCE Trial proved it is in fact not 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% of the cholesterol lowering market. It does not seem that there will be an increase of this percentage anytime soon.

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.

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

  • patient

    This deception hurt us not only health wise but in our pocketbook too. I am a retired patient living on social security and barely have enough money for food. My Doctor prescribed Vytorin and I took it for about a year and a half which means spent lots of money for no health benefit. I think all the patients should get their money back. Also Merck is certainly putting profit before the patients good. How corrupt is that?

  • For the patient who wrote the above comment:

    I’m sorry you have to deal with such issues as this.

    And part of my vocational history was working for Merck for three years selling Zocor. This company once believed, as stated by George Merck decades ago, that the medicines were for the patients, without exception or amendments, and if this premise is followed, then the profits will materialize.

    Profits instead of ethics today, sir, which saddens me as well as many others.

    Thank you for your comment.

  • As a patient using statins for many years, I’m dismayed that pharma would perpetrate such ethical crimes, yet I’m not surprized. I see reps greeting medical office staff with boxes of donuts or designer salads, my magazines are filling up with direct-to-patient ads for obscure and invariably expensive new drugs, etc.

    And now, because of the hefty markup between wholesale cost and patient cost, nephrologists and dialysis clinics are being bribed to corral and encourage the use of such expensive drugs as Aranesp. I’ve seen nurses actually fight over which clinic gets to “serve” a patient.

    Not just the pharmceutical industry, but the medical industry itself is broken. Time to start over.

  • Not true

    The first sentence of this posting is inaccurate and misleading. Obviously the data within ALL trials should be closely examined, only 25 percent to 30 percent of drugs tested in Phase III are successful and go on to receive FDA approval.

    Even less make it to Phase III.

    To say that sponsors usually end up with positive results is just not true.

  • fh comeaux

    No doubt: Vytorin was the responsible element for my childhood’s early death…attacks on the liver, total body lameness through muscle deterioration, chills and high fevers. Within one year and some 60 days of hospitalization, the “bad to worse” syndrome set in: heart failed him.

    The world has suffered more than damages. There must be an end to dangerous drugs!

Dan Abshear

Dan Abshear recently divorced himself from “big pharma” after working for three of the largest pharmaceutical companies in the world for over a decade. He continues to write primarily opinion pieces regarding what may be little known facts about the health care system- particularly the pharmaceutical industry, and his writings also include responses to the related writings of others as well on various internet sites.

Before his pharmaceutical career, he was a patient caregiver for over a decade, which included being a medic (hospital corpsman) in the U.S. Navy and Marine Corps.

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