Vytorin Researcher Accuses Congress of Harassment
21 CommentsBy Ed Silverman // September 18th, 2008 // 8:48 am
Richard Peto - wait, we mean Sir Richard Peto - is having none of it. The House Energy & Commerce Committee may suspect Merck and Schering-Plough are playing hide and seek with important Vytorin data, but the Oxford University researcher is simply sniffing at their questioning - and angrily defends his work and conduct.
In a sharply worded letter dated September 16, he continues to insist there is “no credible evidence” that Vytorin causes cancer. You may recall that the drugmakers unexpectedly revealed preliminary trial results showing an unexpected link to cancer and cancer deaths, causing yet another controversy over the safety and effectiveness of the widely promoted and expensive cholesterol pill (back story).
The drugmakers called the findings an “anomaly” and Peto dismissed the results as a “bizarre hypothesis.” Nonetheless, editorials in The New England Journal of Medicine continued to raise questions. One bluntly stated that “whether the increased mortality risk is due solely to the play of chance is uncertain.”
The House committee, meanwhile, extended its Vytorin probe, which began with the controversial Enhance trial, by insisting the drugmakers turn over Peto’s analysis. The Oxford researcher is running one of two larger Vytorin trials, but the drugmakers initially balked and directed the committee to the FDA, angering committee staffers who then accused Merck and Schering-Plough of providing a secret report.
And this is what led to Peto’s letter this week, in which he reiterates that “the main conclusion (of the SEAS trial) was that the trial results provide ‘no credible evidence’ that (Vytorin) affects cancer rates,” although he doesn’t directly address the NEJM editorial. “It is not in the interests of public health to label potentially useful drugs as unsafe if there is no credible evidence that they are,” he writes. “The key scientific points that our reports make would be selfevidently true to any competent statistician.” And he denies any conflicts of interest.
He then suggests the committee examine its own conflicts of interest; denies being paid directly by the drugmakers for running one of the two ongoing Vytorin trials (although Merck and Schering-Plough provided a grant to Oxford between 2001 and 2009 that’s worth about $64 million); he maintains there is no ’secret report’ given the FDA; and decries the committee’s requests for contracts, communications and other materials as “inappropriate harassment.”
The charge that the committee should examine its own conflict was a reference to a 1994 episode in which John Dingell, a Michigan Democrat who chairs the committee, was criticized for going overboard in investigating a breast-cancer researcher and his trial results. You can read more about that by going to this link and clicking on the second link under the CTSU response to Dingell.
Marilyn Mann
Methinks Sir Richard doth protest too much.
Nathan
This has become a witch-hunt. The bloodthirsty House committee isn’t going to be satisfied until the drug is withdrawn from the market, regardless of what the evidence has to say.
Erik
This is ridiculous. You’re doing research that MAY cause people to get cancer and DOES cost tax payers billions every year.
And you’re unhappy because this causes the government to scrutinize your behavior and financial interests?!
Give me a break.
Justice in MI
Sorry to break the politics of the thread, but a question about current guidelines and those for whom Vytorin and or zetia plus simva might be an option given what we know at this point.
65 year old woman. Genetic hypercholesteremia (TCL well over 300 many years ago when she was thin as rail and athletic). Overweight but not obese. No other risk factors (no diabetes, evidence of CV disease, hypertension, etc.)
Simva alone brings LDL well below 100 and total low 100s, so a “risk ratio” in the mid 2s. Are there any guidelines that wold suggest adding zetia for a pt. like this?
Marilyn Mann
No.
Paul G
Finally someone standing up to this crazy and unproductive dialogue
Vince
And this is what led to Peto’s letter this week, in which he reiterates that “the main conclusion (of the SEAS trial) was that the trial results provide ‘no credible evidence’ that (Vytorin) affects cancer rates,” although he doesn’t directly address the NEJM editorial. “It is not in the interests of public health to label potentially useful drugs as unsafe if there is no credible evidence that they are,” he writes. “The key scientific points that our reports make would be self evidently true to any competent statistician.” And he denies any conflicts of interest.
Sir Richard worries that people might forgo a drug that has not been show to have benefit ‘ this combination has not been proven effective in comparison to its statin component.
However Sir Richard insist that ‘no creditable evidence’ of cancer increase exist meaning that a 90% chance that that occurs just would not statistically speaking creditable.
I believe that the mortality data curve in the HPS study was never given . To do so was described as inappropriate .Was not that study conducted by the same group
Who funds these guys
Justice in MI
Marilyn - Thanks. It will not surprise you that this woman is my wife. If you have a current reference that summarizes guidelines for use of zetia , I would be obliged. Her PCP gave her a page from the Medical Letter which was intended to justify it. I try to stay out of these things when its between family members and their docs, but it’s hard - and maybe dumb - to play dumb.
Paul - I assume you’re referring to Peto, yes?
Marilyn Mann
Most cardiologists would use a statin first to get to LDL goal because the evidence for statins is better than the evidence for other LDL-lowering drugs. If an additional drug is needed, the ACC panel recommended using resins, niacin and fibrates before ezetimibe.
In your wife’s case, you say her LDL is already below 100. Why does her doctor want it lower than that?
I am not an expert, but I believe atorvastatin and rosuvastatin are the most potent statins. If she really needs her LDL lower, it might be possible to do it by switching to one of those.
My husband is on the maximum dose of atorvastatin (Lipitor) and his doctor recently added niacin. However, he has a family history of very early heart attacks (as early as 35 and 40), a very high calcium score (488), and his lipoprotein(a) is high, so he is pretty high risk.
If I were you, I would get a second opinion. I would not want a member of my family to take ezetimibe. In fact, my daughter was on it and I took her off it. There are just too many questions about ezetimibe. It’s just not worth the risk, IMO.
Justice in MI
Thanks for taking the time on this, Marylin. My wife also has a grim family history, but all MIs were men. As I recall, studies at one time sggested that, for women 65+, there was an association between statin use and _increased_ morbidity/mortality (all cause), even when other risk factors present, in the oontext of primary prevention.
I have made my own views clear, but working on a cardio consult for her. Again thanks.
Marilyn Mann
Justice,
You say your wife’s total cholesterol was in the 300s. Does she have heterozygous familial hypercholesterolemia (heFH)? You should know that there were no statin trials with clinical endpoints in people with heFH. It was considered unethical to put people with heFH on a placebo. So the results of the primary prevention trials that were conducted do not really apply to people with heFH. All the observational evidence indicates that the benefits of statins are greater in people with heFH than in ordinary patients. That is because the risk in heFH patients is concentrated in their very high LDL. Statins treat that risk factor directly.
Christopher
There is so much expertise here which makes me reluctant to offer a layman’s opinion but rather like JiM’s wife, I too was stick thin, age 35 and carried a total cholesterol of close to 300 ( I think >269). I didn’t feel as if I did but there it was. I chose not to take statins , but I did follow a simple diet change. And surprise, surprise my total dropped to 192 in a month. The things I was eating - although I thought I knew better (don’t we all) - were the primary cause. All this talk of family history, predisposition etc is OK but ultimately it’s up to us what we shovel down our throats. Please JiM, I am not referring to your wife. It’s simply, once again, back to assuming personal responsibility first, and only then considering drug intervention. Of course, that’s my opinion. I’m 50 now and so far follow roughly the dietary guidelines I was given then. It’s not hard and it’s better than adopting a life-long regimen of drug dependency. And cheaper.
Justice in MI
I feel somewhat embarrassed to have brought Mrs. Justice (actually fellow Dr. Justice) into the good offices of Pharmalot. So I will simply say thanks to Marilyn and, to Christopher: She ate like a bunny and worked (outside) like a horse. Which has also been good for the home life.
Marilyn Mann
Justice,
Can you discuss the evidence for your statement that statins increase morbidity and all-cause mortality in women over 65?
Marilyn
Justice in MI
As memory serves, this was in a presentation by John Abramson who happens to be an old friend. I will contact him for reference.
Christopher
JiM,
As I said I was not directing my comments towards DrMrsJiM. I wouldn’t dream of doing that. My comment was more directed towards the accepting public who willingly undertake a lifetime of medication for something which could be treated by a lifestyle adjustment.
On statins, I’m watching to see more long term use data emerge. I think we know too little of the long term effects these drugs have, especially the more potent ones.
Marilyn Mann
John Abramson wrote a piece that was published in The Lancet, “Are lipid-lowering guidelines evidence-based?” Is that what you are referring to?
Marilyn Mann
I am not in total agreement with John Abramson. I agree that statins are over-prescribed for primary prevention. However, I do not think the mere fact that someone is a woman necessarily means that they should not take a statin for primary prevention (BTW, diabetes is a coronary risk equivalent, so treatment of people with diabetes is not considered primary Prevention). It would depend on their overall cardiovascular risk. Gender is certainly a big part of that, but there are high risk women just like there are high risk men. In any case, the clinical trial evidence Abramson and Wright were discussing in that commentary did not include people with heterozygous familial hypercholesterolemia.
Justice in MI
Thanks, Marilyn - No, this came through conversations with John. I think there is more than what appeared in Lancet - I’ll post if he provides relevant references.
Lipid Guy
Arrogant Brit! His “analysis” may provide a little reassurance, but the jury is out until the results of IMPROVE-IT in 2013-2014. In the meantime, the patients will just have to assume the risk that what they’re taking may increase the cancer incidence and death rate. But don’t worry, Sir Richard Peto is not worried about you!
CJ
The father of cardiology Dr Braunwald of harvard university is perhaps one of the best cardiologists in the world. Sir Richard Peto is arguably the best leading cancer stastician in the Universe as stated by Dr. Braunwald himself.
These two both have stated that Vytorin is not linked to cancer as per SEAS trial, end of story.