Schering-Plough CEO Implies Vytorin Critic Is Biased
20 CommentsBy Ed Silverman // April 2nd, 2008 // 7:36 am
Over the past several years, a big stink has been raised about conflicts of interest, such as when doctors write papers about a particular drug and also serve as a consultant in some fashion to the company that makes the medicine. Right or wrong, pharma regularly defends such situations by explaining that the best specialists are in demand. Generally, drugmakers shrug off the criticism.
Now, though, Fred Hassan is trying to use such a situation to his advantage to deflect the controversy over the Vytorin cholesterol pill. A panel at the American College of Cardiology conference on Sunday was largely dominated by Yale University’s Harlan Krumholz, who skewered the results of the controversial Enhance trial by saying the drug shouldn’t be used as a first or second-line therapy. The study results - released in their entirety for the first time - offered nothing terribly new beyond preliminary data disclosed in January. But Krumholz (pictured to the right) spooked investors, who pummeled shares in Merck and Schering-Plough, which jointly market Vytorin.
Since then, Hassan has been scrambling to do damage control. And now he tells Bloomberg News that the “scientific process was hjiacked,” because there were no opposing views on the ACC panel and questions weren’t taken from the audience. This from a ceo whose company delayed releasing the study for nearly two years; never appointed an independent board; briefly changed the primary endpoint without consulting the primary investigator; and whose senior execs sold huge amounts of stock. Somehow, though, Krumholz is the control freak.
Then, Hassan complains that Krumholz, a cardiologist, once served as a consultant to lawyers who have sued Merck. In a telephone interview with Bloomberg, Krumholz confirmed he had been a consultant in a case involving Merck’s Vioxx. “This isn’t the first time it was disclosed,” Krumholz tells Bloomberg. “It’s a different drug. I understand their strategy is to try to isolate me as a zealot, but this was a consensus.” The other three physicians who worked on the panel “all have impeccable reputations,” he continued. “I have an impeccable reputation.”
Reputations aside, Hassan is free to play attack dog, a calculated strategy, no doubt. And it may resonate well among some people, especially those who are tired of hearing that pharma and docs are regularly conflicted. But Hassan - and Merck ceo Dick Clark, who is happy to let Fred take the heat this week - can no longer complain when pharma is accused of harboring a conflict. From now on, we should expect Schering-Plough and Merck to regularly and fully disclose all potential conflicts up and down the ladder. After all, if the ceo is offended by such arrangements, why shouldn’t the rest of us be concerned?
Steve
I’m getting sick of hearing these doctors who are on the take complaining about conflicts of interests. I expect pharma to be biased, but not doctors.
The MD’s are just hypocrites when it comes to this whole conflict of interest. I suppose Krumholz doesn’t write out is prescriptions with a Zocor pen, right?
snugpharma
Hassan et al, what are you on, ferret juice, stop digging and spreading the dirt hoping it will stick. Your bubble is burst, though your hot air permeates the company
Vince
As I recall Dr. Steven Nissen has also expressed the same concern about this drug.
Chris
There are so many egos in play here it’s tough to see the facts straight but Hassan is doing what he’s supposed to do. The S-P stock has been slaughtered as a result of Kruholz et al’s pronouncement at the ACC which was just that apparently, not a debate. Other than key note lectures all the medical congresses I have attended have allowed Q&A sessions whereas this appears to have been run more like a press conference. Without the chance to ask questions or challenge the opinion - because that’s what it is - the audience was left with a predetermined statement which had enormous consequences.
Many academics and specialists (like Krumholz) thrive on exposure, publications and citations. Few of these are exactly publicity shy and this weekend’s events make that very clear. They carry the mantle of independence because they are physicians but as we’ve seen very few are, and because they are humnan, they are rarely right all the time but that doesn’t prevent them making an unequivocal recommendation on a major stage.
Payback for S-P and Merck without a doubt and perhaps deserved. But they hijacked that event and the consequences have been enormous and in my opinion disproportionate to a still unproven case.
I’ve worked with too many OLs to see them as anything but agenda driven and it’s rarely as altruistic as many would like to believe.
Bob Freeman
Chris, your point is valid. Most KOLs have an agenda and thrive on debate (although apparently not in this case) that will solidify their position in the KOL world.
This is one aspect of the other tread dealing with the establishment of a public authority to conduct comparative clinical trials for effectiveness. The jockeying among KOLs and academic centers for influence will be intense, the net result being a system that is both biased and controversial to the point that credibility will be questionable at best.
Ed Silverman
Hi Chris,
You raise a couple of good points. First, I agree that Hassan is doing his job, which is to aggressively defend his product, assuming the defense is sound and, of course, that point is widely debated right now. As far as Krumholz is concerned, I don’t know about the size of his ego or how the panel morphed as it did into more of a platform, as some have described it. Nor was I defending that outcome.
I was trying to point out the irony - as I see it - of a ceo complaining about conflicts when, often, pharma attempts to play down such conflicts. And so going forward, pharma - and I’m using Fred as the proxy here - shouldn’t be given carte blanche to have it both ways. If conflicts irritate them and smack as being unfair, then they should be more astute about explaining conflicts as unavoidable, business-as-usual situations simply because it’s convenient.
Regards
ed
Chris
Hi Ed
I understand your post and the point about conflicts. I wasn’t really addressing that but instead the rather disturbing mugging that took place at ACC. I took that as the main emphasis in the Bloomberg report in your post, more than the reference to Krumholz’s conflict. I think Hassan’s point is that at a scientific conference which attracted 10,000 cardiologists and featured a ‘consensus’ developed by 4, it’s reasonable to think that the other 9,996 might have a say. They weren’t permitted to though, and the consequence of that is profound.
I don’t know Krumholz and I may be completely wrong in assuming his hat size is of the larger variety favored by many other ‘leaders of medical opinion’. My sense is that S-P and Merck’s behavior angered them and their colleagues and this was time to give back some of the pain. And owning the ACC stage, along with a highly-developed sense of timing, made that all the more public.
All the accusations about execs dumping stock remain to be proven, if at all. For now all I can see is that S-P and Merck operated in a less than transparent way in delaying the results of a trial which, let’s remember, did not conceal serious side effects, AEs or mortality. The drug is not harmful and it has so far proven, apparently, to be an effective treatment for some. Now S-P and Merck are being hammered because the powerful ‘opinion leader’ lobby was irked at the perceived sleight by the same companies which in other times was (and will be) better regarded.
Forgive the cynicism. I am no lover of S-P or Merck, but the ACC has not distinguished itself in allowing this circus to take place. That is not how scientific discourse should take place and I sense that is Hassan’s point (and of course, his best rebuttal just now).
SPRI
Hassan is simply a horse’s backside. If people really look at his record, as well as that of Cox and the rest of his cronies, it’s all been smoke and mirrors. get away with whatever you can, make the financials look good, deny responsibility for anything that goes wrong, point the finger at somebody else, and then run away with all the money. It happened at AHP, at Pharmacia, and it’s happening at Schering. I’m sure he’s sorry he didn’t take advantage like many of his team did. Now he has to really work for his pay. I have no respect for him or Richard Clarke. They have damaged their companies, probably beyond repair.
Harlan Krumholz
I appreciate the concern raised by Chris and understand that Ed, who does not know me, cannot vouch for me — but they and others should understand what happened. The panel consisted of four physicians with experience in research, teaching and clinical care - one who is in full time private practice - two who are experts in the education of physicians - and one (me) who has particular expertise in research that promotes improvements in clinical decision-making and health care delivery. We were asked to comment on the ENHANCE study and discovered over the course of several weeks of discussion that we had a clear consensus about the recommendations for practice. My comments reflected that consensus — and were consistent with two editorials in the New England Journal of Medicine — and with the published guidelines. The ENHANCE study was not definitive, but increased uncertainty about the ability of ezetimibe to improve patient outcomes. We did not say that we know — since the study of patient outcomes has not been done - but concluded that until that information is available physicians and patients should first go to the medications for which we have strong evidence. The study is important because it occurred in the context of a practice pattern in which this drug represented about 15% of all lipid lowering agent prescriptions (in contrast to 3% in Canada) — and raised important questions about whether ezetimibe was being used in front of more established agents (esp statins). No one on the panel had an axe to grind against industry in general or these companies in particular. And I am very sorry for anyone who has suffered as a result of what happened to the companies — but the bottom line is that we need to do what is in the best interests of the patients given the information that is available at this time. I just wish the companies had invested in a clinical outcomes trial earlier so we would know the answer now. As it stands, the trial result will not be known until at least 2012 — so in the meantime we need to stick with drugs that we have some degree of certainty of benefit (for those patients who need medication).
Chris
Thanks for taking the time to respond to these comments. What interested me were the following:
- I wasn’t at the conference but I understand that your consensus was presented in a forum that did not include discussion, debate, Q&A and therefore a possible alternative view. Undoubtedly the panel’s credentials are excellent but is it possible that some of the audience might have had other experiences and observations that could have added to the debate?
- It’s not clear from your message whether you were asked to comment on the ENHANCE study or to do that and then recommend guidelines for practice
- My experience is that practice guidelines are drafted, reviewed, hashed, re-hashed, re-drafted and presented for peer review before presentation because once disseminated they become accepted to a large degree not just by prescribers but also by analysts
- Do we know if ezetimibe (Vytorin?) is being used in front of other more established medications (statins) or just that it accounts for 15% of prescriptions? Isn’t there a difference and if so could it be that it is already being used where you direct? The danger is that many existing prescribers will hear about this consensus – whether in peer review journals or just as likely the lay press – and abandon the drug altogether
- We’re not talking Bear Stearns but there are many workers at both companies whose stockholdings – and pensions – have been significantly affected by this week’s response to the announcements.
There are no winners from this but there are profound consequences of the weekend’s events which might have been tempered with a more inclusive approach.
Doc
To Chris and Ed,
Hassan is just doing his job defending the company and drug???? I thought that SGP was a pharma company? I would hope that his first job was to assure that his drugs and data are timely, honest, free of bias and ethically promoted with full disclosure. Then he might need to assure that his exec team isn’t trading on inside info, which disadvantages all other stockholders. THEN, he can defend his company and drug.
Chris
Doc,
As you say SPG is a company ie a business. That means the CEO has responsibility to employees, patients, healthcare professionals and investors. I think what he’s doing is responding to just those groups and I understand he’ll have his chance to rebut the claims of insider trading later. Your final point doesn’t account for the realities of the market, which in turn affect shareholders, many of whom are employees: if SPG believes it is already complying with the other items on your list (I don’t know but assume it does) he must deal with that first because as thie week’s events have shown, the America stock market is hugely volatile, brittle and hyper-sensitive to whiffs of bad news, let alone what followed ACC. So yes, he’s doing his job.
Ed Silverman
Hi Doc,
Well, yes, it’s his job to defend his product and company - assuming the defense is sound, which is being widely debated right now. That’s what I wrote earlier and I deliberately added that caveat. That’s not the same thing as agreeing with his position.
If his position isn’t sound - if his drug and data weren’t ‘timely, honest, free of bias and ethically promoted with full disclosure,’ as you noted - then he should suffer the consequences. Does this help?
Regards
ed
Health Blog : Vytorin Postgame: Dueling Opinions
[...] Krumholz posted a comment to a blog post that highlighted Hassan’s comments, and emailed the blog Pharmalot with this [...]
MVP
Hi Dr. Krumholz,
I am currently using 10/40 Vytorin and one of the reasons my Cardiologist prescribed this medication is that he felt it had a better profile in terms of its effect on the liver. He showed me data which suggested that the combination with the lower statin dose had a similar or even better LDL lowering profile than higher doses of simvastatin or etorvastatin alone. Since (as far as I can tell) no statin has been proven to reduce plaque using imaging studies should we be judging Vytorin so harshly? I’ve also read that the outcome study for Lipitor which claims a 34% reduction of heart attacks was really the difference of 1 case (3 heart attacks on Placebo and 2 on Lipitor)? So, the ultimate question should be, has the frequency of heart attacks been significantly reduced since LDL lowering agents have become available? If that is true then it seems that any drug which does this and exhibits an improved safety profile should be considered an advancement and should not be held to a higher standard than any other LDL lowering agent.
Conn
The big thing that Dr. Krumholz doesn’t address is that many, many patients have had good outcomes in reducing LDL with Vytorin. How does he explain how thousands of patients who have had their LDL reduced at much higher rates after they were switched a statin to Vytorin. It is not luck, there has to be some clinical benefit with the addition of Zetia. To say as he implied that Zetia might be a placebo effect seems to me to carry some sort of vendetta since the medical science does not support that in clinical practice.
The other thing that he doesn’t address is that to get the clinical benefit of using a statin like Lipitor to get the benefit of reducing heart attacks was a small study. To get this effect you have to go to the highest dose of these statin drugs which many people cannot tolerate. Personally I have known many people who could not tolerate statins at all even in the lowest dose. One person in particular told me he had the worst muscle soreness he had ever had and it felt like he had the flu and ending up losing over 10 pounds before he discontinued the statin. To scare people aware from a potential product is medically imprudent in my eyes.
Doc
Ed & Chris,
Yes it helps. I actually think Hassan has done a great job of turning the corp around, shame its gotten to this, but I still say he needs to look in the mirror more on this one.
Ethicist
Question for Dr. Krumholz
You describe yourself as having an impeccable reputation. Did you not think it important to disclose at the time of the ACC panel that you have been paid more than $10,000 to serve on an advisory board at United Health Care which has spent millions of dollars on Vytorin and Zetia?
Interested Watcher
Patients should be concern with the fact that some doctors will follow Dr. Krumholz’s recommendations. Let’s see, why don’t we put patients back on a statin only plan…jack up the dose and see what happens. I think they’ve done that and it didn’t work.
I believe that shareholders of MRK and SGP should point their class actions law suits at Dr. Krumholz for his drastic misrepresentation, brash tone and over aggressive show boating actions during Sunday’s presentation. He has not only put patients in danger but has also lead to the destruction of Billions of dollars in value in both MRK and SGP.
Orlando
It is apparent to me (a medical professional) that most of the comments I have read have come from people ignorant of cardiovascular issues and complete knowledge of all the data on statins and other lipid lowering agents. Just reducing LDL is not the issue and not what “good doctors” strive for. The evidence (if you knew it) shows that it is not just about hitting a magic number that prevents heart attacks and strokes - rather it is what agent you use to achieve that goal!
As Dr Krumholz stated in his presentation, we have evidence of agents that lower LDL significantly such as HRT and torceptrapib. But these agents also carry a significant risk of death! As physicians, we need first to use agents that yes, lower LDL but that have “PROOF” from large scale clinical trials that they can prevent heart attack and stroke! And that those agents can do this safely! Statins are used by millions of people worldwide with few side effects and serious consequences.And every statin I have seen brought to market has had evidence of reduction in risk of CV events and regression of plaque data within three years of it coming to market. Zetia has been on the market for “6 YEARS”! So we as physicians are supposed to blindly use an unproven product and one that could potentially do HARM to our patients because S-P and Merck say so?
I believe that we have saved many lives by using statins as first line agents. And the ACC panel did not tell us not to use Zetia, but to reserve it as a last resort, or for those patients who are truly statin intolerant. I applaud Dr Krumholz and the ACC panel because their ultimate goal is to do what is best for the patients! For those who condemn him for his comments; first, educate yourself fully in the disease state/treatments before you make ignorant comments, and second, it is not about the money or the stock or the conspiracies - it is the health and safety of you, the patient, that forces us to research and collect as much data as possible about the agents prescribed to you.
Does it make myself and other physicians angry when S-P and Merck hide that data from us for 18 months? You BET IT DOES!