As part of its ongoing investigation into the Vytorin controversy, the Senate Finance Committee is disclosing angry notes written by John Kastelein, who was the primary investigator for the Enhance trial, which found the cholesterol pill was something of a dud. The costly combination of Merck's Zocor and Schering-Plough's Zetia failed to show a benefit over the much cheaper Zocor in reducing plaque in the carotid artery, and even showed a statistically insignificant buildup, although it did a better job of lowering LDL in patients with an inherited form of high cholesterol.
In other words, Vytorin may not be of much use as a first or second-line therapy, a fact underscored by several prominent docs when the complete Enhance data was dissected at the American College of Cardiology conference this past weekend. And the drugmakers are under a microscope for the way they handled the data - they delayed releasing the study for nearly two years; never appointed an independent board; briefly changed the primary endpoint without consulting Kastelein, and some Schering-Plough execs sold huge amounts of stock.
And so the Senate Finance Committee is trying to connects various dots, such as contributions made by Merck and Schering-Plough to the ACC, which urged its members not to panic when the drugmakers two months ago issued preliminary data. Since 2003, Merck and its various foundations and divisions have donated almost $5 million to the ACC for conference booths, expo fees, educational seminars, and satellite event fees. Schering-Plough gave $1 million. Their joint venture gave another $5 million.
Then there's Schering-Plough's '49 Plan' to wine and dine docs in hopes of convincing them to prescribe Zetia, on which $3.5 million is being spent and was first reported by Pharmalot. To keep the pressure on, letters were sent today to Merck and Schering-Plough seeking info about payments to docs. Meanwhile, this is an excerpt from Kastelein's e-mails to John Strony, a Schering Plough exec:
"Is it correct that (Schering-Plough) has decided not to present at (the American Heart Association), but to await the two other, completely unvalidated, endpoints, which analysis is going to take us straight into 2008??!!?? If this is true, (Schering-Plough) must have taken this decision without even the semblance of decency to consult me as (primary investigator) of the study. I can tell you that if this is the case, our collaboration is over...This starts smelling like extending the publication for no other (than) political reasons and I cannot live with that."
The next day, Kastelein wrote again to Strony to say that "I have been travelling half the globe in the last 6 months to a number of large and important meetings at the strong wish of Merck to chair them or to present ezetimibe (Vytorin) data. At every single one of them, I was cleared to say that Enhance would be presented at AHA. There is no reason whatsoever to include femorals; you will be seen as a company that tries to hide something and I will be perceived as being in bed with you!"
In a statement, Grassley says that he is "troubled that (Merck/Schering-Plough) may be placing marketing interests above science. For instance, in an M/SP marketing review done just last December, it appears that advancing sales, not science, was the priority. Page eight of the document details messaging adjustments for 2008 such as 'Incorporate lower is better into message flow' and 'incorporate switch message - SNAG (simvastatin not at goal).' Another slide show created by your respective companies last year noted that, 'History has shown that ZETIA is extremely sensitive to promotion, with consistent share growth demonstrated when fully promoted.' "
19 Comments
"it appears that advancing sales, not science, was the priority." What rock has this doc been living under? Does ANYONE with a brain think that pharma has any other objective than dollars? Come on, I've been in this business too long to see this kind of naivete. And the docs say "pharma reps and companies dont influence me" - right, and monkeys fly out my as*.
I've been in it for a long time too and have seen this type of response from an 'opinion leader' who feels slighted. Aside from the rights and wrongs of the case, the retaliatory force of an 'OL' who feels slighted is something to behold. And of course we shouldn't let the famous four whose full court press initiative positioned them today as - yes - leaders of opinion for the 30,000 other cardiologists in the country. Hell hath no fury like an 'OL' scorned. Been there, got the scars!
Unfortunately, there was no open scientific forum as promised. It was a self selected group of OL's telling the world about their opinion - without discussion, without questions, without answers, without debate.
ACC should be embarrassed.
Grassley should be ashamed to be doing nothing for the overall healthcare system and because of this ineptitude of congress, they keep looking for distractions to keep the public away from focusing on the real fundamental problems that congress should worry about.
Of course, the companies should not be off the hook, but Grassley at al should not be using these red-herrings to pretend they are doing something when they are not.
What a disgrace of a debate; we must be the laughing stock of the world - once again.
Dr Kastelein should remember the old European saying "When you sup with the devil use a long spoon!"
I really hope that this gets the full spotlight attention that this story deserves. If there was ever any other proof needed for why it is so important for us all to be more mindful of what and who we are trying to "seduce".
The crushing costs of these drugs are causing governments and patients to demand to know exactly how and what they do and if they perform as promised. What did we think would happen?
You may call the PI in this case naive, but I have to say we in pharma are naive. How do we think we can keep doing what we do and not draw this kind of attention to ourselves? Perhaps the PI in this case will go on a speaker tour to teach doctors how to be more careful when choosing their dancing partners...
What the public and patients are asking (and I remind us all, that there is no us/them, one day we will get sick and need the very drugs we make)is to understand why we are having a hard time accessing health care.
Shame on the ACC for taking all this money from Merck. But shame on Merck for wasting all that money. The ACC didn't need it and as it turns out Merck couldn't afford it either.
One of the major reasons why this is such the fiasco that it is is the DTC. Drug sales were near 5 billion. You should note that one report stated that sales were far less in Canada precisely because there is no DTC. We should really stop DTC.
Ed, how did the DTC conference go yesterday? Can you share anything?
I am embarrassed that my Merck has been lowered to this money grubbing over ethics. At Merck I was fed the mother's milk of ethics and service to the patients ("Medicine is for the patients, not the profits.")--This doesn't match my expectations of Merck at all.
Even in the dark days of Vioxx, I could reassure myself that Merck had taken masochistically ethical action and pulled Vioxx and exposed themselves to great liability, when the Celebrex strategy successfully executed by Pfizer (keeping it on the marked with a black box warning and restricted marketing) was more expedient and safe.
FPME,
The Canada DTC issue is far overblown. The major factor in lower use in Canada has less to do with DTC than it does with payer decisions. A number of provinces have very limited access to Vytorin, leading to dampened sales. In the US, if payers denied payment for a drug, DTC would have only modest impact on sales. However, many US payers (health plans, PBMs, etc.) saw Vytorin as a means of combatting Lipitor. Merck/S-P were very aggressive in rebating, leading to relatively strong access and, ultimately, strong sales spurred on by DTC.
Altex,
You are entitled to your opinion. Have you questioned why certain provinces would have limited access to it? That is because in order for it to be reimbursed and on the provincial formulary, the data probably wasn't conclusive enough.
DTC instigates patient awareness which in turn instigates the patient to more actively seek the drug and advocate for reimbursements.
I would have to agree with you on the competition created with regards to lipitor and getting better pricing for it. However, it underscores the fact that "bean counters" cannot make decisions based on pricing alone. In the end we see that Vytorin doesn't work, so they were not really comparing apples to apples we they? Additionally, this is a risky game to play just to attack a competitor. It almost suggests that patients were used as a means to an end...
[...] of the two drugs. Investigators at the Senate Finance Committee, in fact, have just released the text of several angry emails Kastelein wrote to a Schering executive as delays mounted. “This starts smelling like extending the publication for no other (than) [...]
As usual, Atlex is right. Although highly visible, the costs of DTC advertising are a much lower percentage of total costs than people expect.
There is Canadian DTC, but it is a lot weaker in messaging than in the US. You can either mention the drug or the condition but not both. It is generally Pfizer and GSK spending the money. Twinrix is promoted heavily and the ubiquitous Viagra ads.
I was surprised to hear that Vytorin was in Canada, so I checked the TPD website and it doesn't show up there. Are you sure it is approved?
I agree with Atlex, the percentage of expense to the A&P spend of DTC would be minor compared to sales effort or CHE or "entertainment".
[...] For Schering Plough: “Hell hath no fury like an Opinion Leader scorned!” For Dr John Kastelein (pic): ” When you sup with the devil - use a long spoon!” For Merck: “If you lie down with dogs expect to wake up with fleas!” Ed has the story. [...]
Bruce, since you are current on this--do Canadian TV stations still block DTC ads from the US (like from Detroit or Buffalo) stations? My recollection is that until 9 PM such ads are blocked.
While Googling....
FYI for anyone interested, Canadian drug advertising Act:
Scope
This policy applies to all types of information disseminated in relation to drugs for use in humans.
Background
There are numerous provisions within the Food and Drugs Act and Regulations that apply to drug advertising. In order to determine the applicability of those provisions it is first necessary to determine whether or not a particular message can be considered to be advertising. For the purposes of the Act, advertising is defined as including "any representation by any means whatever for the purpose of promoting directly or indirectly the sale or disposal of any food, drug, cosmetic or device". If a message regarding a drug is not considered to promote sale or disposal, it is not subject to the advertising provisions of the Food and Drugs Act and Regulations.
There is a particular need to distinguish between advertising and non-promotional information in the following situations:
1. Prior to market authorization:
* promotion of a drug prior to market authorization is not permitted (Section 9(1) of the Act, Section C.08 002 of the Regulations) because the terms of such authorization have not been established and the proposed indication(s) for use have not been verified.
2. After market authorization when information on a drug is disseminated to the general public:
* promotion of a prescription drug (Schedule F) to the general public is limited to name, price and quantity (Section C.01.044 of the Regulations).
* a drug (prescription or nonprescription) may not be advertised to the general public for the treatment, preventative or cure for any Schedule A disease (Section 3 of the Act).
Here is more This is from the recommendations from Health Council Canada regarding DTC and is related to what Merck spent on Vioxx. I include this here so that we can understand how the situation with Vioxx and now this Vytorin situation can impact future programs... Direct-to-consumer advertising of prescription drugs is highly controversial, with many competing claims made about potential benefits and harms. Merck’s global withdrawal of the arthritis drug rofecoxib (Vioxx) in September 2004 has prompted much media discussion of the effects of DTCA on public safety.
Merck had spent more than US $500 million advertising Vioxx to the US public in its five years on the market. In 2000, consumer directed advertising spending for Vioxx surpassed spending for Pepsi-Cola.
2 US cardiologist Eric Topol argued in the New England Journal of Medicine that by not stopping Merck from advertising Vioxx to the US public while evidence of cardiac risks grew, the Food and Drug Administration (FDA) had failed in its duty to protect public health.3 Just weeks earlier, Peter Wold-Olsen, President of Merck’s Europe, Middle East and Africa Human Health Division, was quoted in Scrip pharmaceutical bulletin arguing that many Europeans were suffering or dying needlessly due to “patient information deprivation syndrome” of epidemic proportions caused by the European ban on DTCA.4
From the Executive Summary:
This paper examines these claims in light of evidence from research and international experience – and concludes that there is no reliable evidence to support them. For example: • Analyses of print and broadcast ads in the US have found that information on drug benefits received substantially more space and time than information on risks, and that key information for informed health care choices, such as how likely a drug is to work or treatment alternatives, is usually missing. • In a New Zealand survey answered by half the country’s GPs, nearly seven out of 10 reported having felt pressured by patients to prescribe advertised medicines. In 2003, professors of general practice at four New Zealand medical schools called for a ban on DTCA. • In a study of 78 primary care physicians’ offices in both the US and Canada, nearly all patients who requested advertised drugs received one or more new prescriptions. These patients were 17 times as likely as other patients to receive one or more new prescriptions during the consultation. • A systematic review of research on DTCA concluded that “DTCA does influence patient demand and doctor prescribing behaviour. No evidence of health benefit was found since this had not been examined in any detail [in published research]. . . The onus is on those who might support DTCA to produce evidence of benefit and, in the absence of this evidence, we must assume that the likely disbenefits (clinical and economic) outweigh the as yet unproven benefits.”
The Parliamentary Standing Committee on Health, in its 2004 report Opening the Medicine Cabinet, has recommended that Health Canada should: • immediately enforce the current prohibition of all industry-sponsored advertisements on prescription drugs to the public; • ensure the provision of independent, unbiased and publicly financed information on prescription drugs to Canadians; • dedicate specific resources to vigorously enforce DTCA regulations, including active surveillance, identification of potential infractions, appropriate corrective action and annual reports; • ensure that all complaints about DTCA sent to Advertising Standards Canada and the Pharmaceutical Advertising Advisory Board are forwarded to Health Canada for investigation and action.
These conclusions were supported across the political spectrum. However, there has been little discussion on implementation since the report’s release. 5
FPME: • In a study of 78 primary care physicians’ offices in both the US and Canada, nearly all patients who requested advertised drugs received one or more new prescriptions. These patients were 17 times as likely as other patients to receive one or more new prescriptions during the consultation.
...I don't know the methods of this study but it seems impossible, from what my gut tells me. I think patients have a greater than 1/17 chance of getting a new script/doc visit. So I would think that even if 100% of patients who asked for a med from a commercial got it, it still couldn't increase new scripts 17X.
Hi Bob, I actually just moved to the USA from Canada, so this discussion is quite interesting. Most households in Canada have cable tv and all cable providers will substitute Canadian commercials over the US ones. But you sometimes see them on the lower scale channels, like A&E, HGTV etc. Most of the media spend for DTC is focused. Twinrix is on social channels like the HGTVs, Travel channel, food network.
FPME: As late as September I had discussion with the Pharmaceutical Advertising Advisory Board chairman on DTCA and he said that he would provide guidance on any new ad, but Health Canada "regulates" it. Not much regulation happening since there isn't a huge backlash in Canada against. Yes there is some resistance, but not as organized as here.
Many thanks, Bruce.
Bruce,
Regarding what you say about Health Canada regulating it, this is my understanding as well - so thanks.