Merck Takes Another Round
Merck has won its first Vioxx caase in federal court, and is now 2 for 3 overall. Merck has vowed to fight each case individually, which seems to be the right strategy given the unusual circumstances involved here.
Here's the situation as I understand it. Vioxx is an anti-inflammatory that conveniently doesn't irritate the digestive tract and so is much in demand for older people with arthritis. (About 6 years ago I had a wicked case of tendinitis in my left elbow. The orthopedic gave me a shot of cortisone and prescribed Vioxx. But my health-care provider refused to cover it, claiming it was no more effective than Advil. The doctor kindly handed me a pile of samples, and I've lived to tell about it.)
Sometime after Vioxx entered the market, further clinical trials showed conclusively that Vioxx was causing some of its patients to have heart attacks. The link is statistically undeniable, but the actual mechanism is not known. Extrapolated to the general population of Vioxx users, the victims would number in the tens of thousands- and it's clear that Merck management knew this for a few years and withheld it. So Merck essentially sat back and watched while thousands perished using its deadly drug. Yet who's to say that any given heart attack was caused by Vioxx use, since statistically tens of thousands would have had heart attacks without Vioxx? Our legal system requires that legal liability be established in an actual specific case - there's no provision for anyone bringing to court a general liability claim. Even a class-action has to be able to identify specific plaintiffs.
Large settlements have been made with far less certainty of wrong doing - Erin Brokovich's chromium-6 case being a good example. But when faced with victims of terrible - and rare - diseases, a jury is far more easily convinced of malfeasance, despite inconclusive scientific evidence. But heart disease is the biggest cause of death in the country - everybody knows at least a few people who've had them. And since it's not known exactly how Vioxx brings one on, Merck is smart to fight these cases individually, daring the victims to prove that their heart attack was one of the ones caused by Vioxx rather than like all the other run-of-the-mill heart attacks.
I would think a good argument could be made that Merck management is guilty of manslaughter by allowing their drug to continue to be used knowing that thousands would die. But, again, for a crime to be proven, you need a victim - you can't be convicted of statistical murder. Fascinating.
Here's the situation as I understand it. Vioxx is an anti-inflammatory that conveniently doesn't irritate the digestive tract and so is much in demand for older people with arthritis. (About 6 years ago I had a wicked case of tendinitis in my left elbow. The orthopedic gave me a shot of cortisone and prescribed Vioxx. But my health-care provider refused to cover it, claiming it was no more effective than Advil. The doctor kindly handed me a pile of samples, and I've lived to tell about it.)
Sometime after Vioxx entered the market, further clinical trials showed conclusively that Vioxx was causing some of its patients to have heart attacks. The link is statistically undeniable, but the actual mechanism is not known. Extrapolated to the general population of Vioxx users, the victims would number in the tens of thousands- and it's clear that Merck management knew this for a few years and withheld it. So Merck essentially sat back and watched while thousands perished using its deadly drug. Yet who's to say that any given heart attack was caused by Vioxx use, since statistically tens of thousands would have had heart attacks without Vioxx? Our legal system requires that legal liability be established in an actual specific case - there's no provision for anyone bringing to court a general liability claim. Even a class-action has to be able to identify specific plaintiffs.
Large settlements have been made with far less certainty of wrong doing - Erin Brokovich's chromium-6 case being a good example. But when faced with victims of terrible - and rare - diseases, a jury is far more easily convinced of malfeasance, despite inconclusive scientific evidence. But heart disease is the biggest cause of death in the country - everybody knows at least a few people who've had them. And since it's not known exactly how Vioxx brings one on, Merck is smart to fight these cases individually, daring the victims to prove that their heart attack was one of the ones caused by Vioxx rather than like all the other run-of-the-mill heart attacks.
I would think a good argument could be made that Merck management is guilty of manslaughter by allowing their drug to continue to be used knowing that thousands would die. But, again, for a crime to be proven, you need a victim - you can't be convicted of statistical murder. Fascinating.
posted by ziel | 2/18/2006 07:27:00 AM
21 Comments:
Muddying the waters further is the fact that a high percentage of Vioxx users were elderly, and therefore facing elevated risks of heart disease even without Vioxx. Proving cause-and-effect consequently is quite difficult.
Peter
Iron Rails & Iron Weights
That's what they're counting on. There really should be some other legal means to make them accountable - or at least to have some accountability in the future. Don't hold your breath, though. The public couldn't be less outraged. Amazing.
I think this is something of a boy-who-cried-wolf problem. The public has been continually told for so long by the self-appointed tribunes of the people that corporations were always lying to, ripping off, or in general trying to kill them, and people don't see it happen (because gross malfeasance of this type is pretty rare), so they tend to not get too bent out of shape when it does happen.
Well that could be. An alternative is that Americans, bizarrely, find it hard to believe that a pill you take every day could give you a heart attack while finding it completely credible that some mysterious chemical (like dioxin or chromium 6) stored in tiny amounts in the ground somehow finds its way into the body causing a macabre smorgasborg of deadly cancers among some tiny percentage of residents.
You may be right though - people may be losing their patience with chemical scares.
Another alternative explanation is that enough people have some serious money in Merck stock that the outrage can't get a foothold.
The press isn't excited about it - although we're talking tens of thousands of deaths.
Looks as if I'll have to do it myself. God Damn it, doesn't _anyone_ do their fucking job anymore? Do I have to do _everything?_ Am I supposed to tear a new asshole in evolutionary biology, mock an insane foreign policy _and_ clean up big pharma? Jesus H. Christ.
Yes, Yes, and Yes! And that's just for starters, right?
According to this post by Colby Cosh, the problem is that the drugs were being prescribe to people who shouldn't have taken NSAID drugs in the first place.
Essentially, according to Dr. Michael Schweitzer, normal NSAIDS (Advil and Ibuprofen, I think) can cause the same side effects as Vioxx in people over 65, which is why they are not prescribed to people over 65. They also hurt the digestive tract. Vioxx, Celebrex, and other COX-2 only NSAIDs do not hurt the digestive tract, but the other side effects (kidney and heart problems) remain.
The way that the new NSAIDs have been marketed, people assume that the deadly side effects of NSAIDS are eliminated in Vioxx and Celebrex, when in reality, only the annoying ones are. Or, alternately, they assume that the merely annoying side effects were the reason why they are not prescribed to people over 65.
In short, the drugs were falsely advertised to the markets that should not have taken them.
Non-steroidal anti-inflammatory drugs (COX-1 and COX-2 inhibitors) like Tylenol, Aspirin, and Ibuprofen kill somewhere between 10,000 - 20,000 users per year. (and that is according to the FDA) http://www.arthritisreliefhelp.info/Arthritis-and-Pain-Relief-Medications-cause-16-500-deaths-per-year.php
As you know, COX-1 is the enzyme that protects your guts. Tylenol, etc will eat away at it. COX-2 prevents pain. So...you get pain relief with your guts being torn up. Vioxx inhibited only COX-2. It was a miracle drug (and still is). So, for people with horrid arthritis they could take Vioxx every day and not have their GI tract destroyed. In addition, Vioxx was not a narcotic. So, if you had horrible pain, you could take Vioxx instead of a narcotic and not have to walk through life in a dazed stupor.
The VIGOR study that resulted in Vioxx's withdrawal only showed a negligible increase in cardio problems. And no causation was shown. Remember, the worry warts at the FDA didn't even ask Merck to pull the drug! This is the same FDA that regulates how many pieces of pepperoni go on your frozen pizza. The FDA never recommended that Merck pull the drug! Yes, that's true. But those evil manslaughter-committing directors at Merck pulled their best selling drug off the market.
The other COX-2 inhibitor on the market (Celebrex) doesn't work nearly as well as Vioxx. What are we left with now? Chew your aspirin , which kills 10-20,000 people per year and sends 100,000 people per year to the ER with GI bleeds. And, if you have horrible arthritis, you lie in bed in agony while lawyers, bureaucrats, and blogger-type know-it-alls tell you how much better your life is now that Merck is being sued into oblivion.
I believe anonymous is overstating the case. It is true that vioxx is MUCH safer than Aspirin, but so are other things. The heart attacks are a marginal effect that probably push it over edge of being worse than the next option.
Glaivester - anonymous basically said this, but didn't make it clear he was directly contradicting you: stomach problems aren't merely annoying; they're deadly, much, much worse than other problems with aspirin.
Wouldn't it have been a lot better if Merck had immediately go with some very cautionary labeling once the potential dangers became apparent rather than fighting the FDA tooth-and-nail over warnings then withdrawing the drug entirely once the build up of the evidence exploded in their faces?
The VIGOR study that resulted in Vioxx's withdrawal only showed a negligible increase in cardio problems.
Negligible is fine for a drug with a very limited target base - but when you're marketing to millions, it's a different ballgame. I had Vioxx prescribed to me for tennis elbow, for godsake, with no history of GI troubles. Do you really think the doctor would have been throwing samples at me if he had known it had a statistically significant cardiac risk?
L - worse than what option? If you had a 1% increase in heart attack risk or a choice of lying in bed in horrible pain, which would you choose?
Zeil - You make a great point. Fortunately, that is exactly what Merck did in 2002 when the FDA, after reviewing the VIGOR study, recommended a stronger warning label on Vioxx. The label was changed in 2002. http://www.fda.gov/bbs/topics/news/2004/NEW01122.html
Lastly, what has not been mentioned is that the VIGOR study compared Vioxx to naproxyn. Naproxyn is similar to aspirin in that it has a cardio-protective effect. Merck always said that Vioxx did not have this cardio-protective effect.
OK...so, that wasn't my last point. LASTLY, virtually all the plaintiffs in this suit all older, obese, former smokers, many of whom have a history of cardiovascular problems.
Lying Eyes - maybe you should do your homework before you start throwing around words like manslaughter.
(And no I don't work for Merck, nor am I affiliated with them by any means.)
I looked up the real numbers on the relative risks of vioxx and aspirin and other old-fashioned NSAIDS. The risk of death from gastric bleeds for people using old-fashioned NSAIDS (including aspirin) is about 1.5 x 10-4 per year. (Lanas et al, Am J Gastroenterol. 2005 Aug;100(8):1685-93) Vioxx cut that risk by two-thirds.
Unfortunately, it doubled heart attack rates (meta-analysis by Juni et al, Lancet November 5 2004), which increased heart attacks by about 5 x 10-3 per year, about 30-40% of which are expected to be fatal. So, on the one hand it reduced one kind of risk by about 1.0 x 10-4 per year while increasing another kind of risk by about 1.5 x 10-3.
Fifteen times and what do you get?
With those risk numbers, it is hard to imagine any subpopulation that would have a net benefit from Vioxx. Old people are more prone to bleeds, but they're also more prone to heart attacks.
And yes, there is a candidate mechanism.
The VIGOR study showed that vioxx caused a four-fold increase in heart attack risk over naproxen. There is no evidence of any cardioprotective effect in naproxen: it would have to drop heart attack risk by 75% to explain the results, much more than aspirin does. Meta-analysis suggests a slight protective effect (RR of 0.86), but zero effect s obviously in the confidence interval.
The people at the New England Journal of Medicine and the Lancet are mighty pissed: and they know what they're talking about.
We've haven't gotten into the part about Merck knowing the gist of this for four years, having their drug reps lie about cardio risks, threatening researchers and suing journals that talked about the emerging cardio risks.
Few physicians were aware of these risks, even though a close reading of the journals would have suggested it - because hardly any physicians read the journals.
The most illuminating discussion of the pros & cons of Vioxx and cv problems that I've yet read. Thanks Lyin', ziel, Russell, gcochran, and glaivester for the back-and-forth. Anonymous, too, whatever your screen name might be.
Mr. Cochran,
Yes, you do have a point and I'm not arguing that Merck did everything perfectly. However, the actual number of people who represent the 4x increase in CV problems is 2 to 8 people out of 1,000 or 1,500. I think it was out of 1,500 in the Vigor. It was not exactly a bloodbath.
There was no causation determined. So, the question of what happened is still unknown. Merck shouldn't be considered guilty until proven innocent. Not only that, they put the strongest warning label possible on Vioxx.
In addition, the FDA is never mentioned in the discussion over Vioxx. As a lawyer, I understand that compliance with a regulation does not mean that you are not negligent. However, as a citizen who has a good chance of being killed by an FDA reg when I'm older, I have to ask, "isn't FDA approval worth something?"
We have one of the most rigorous drug approval processes in the world here. It takes about 7 years to get a drug through the FDA. Dying of cancer and want to sign a waiver to get a new experimental drug? The bureaucrats at the FDA tell you to go to hell. Not to take the conversation into a totally new area, but I just want to point out that it's not as if Merck scientists cooked up Vioxx in a lab on Monday and put it on the shelves on Friday. Vioxx underwent pretty rigorous testing. And the net of all this is that we still don't know what the hell caused the increased CV events in the Vigor trial.
Lastly, naproxyn does have a cardio protective effect. Sure, perhaps not enough to account for the variation between VIGOR and the earlier studies, but the effect is there.
Best,
Anonymous (a.k.a. "M")
Mr. Anonymous - "M". You are mistaken. The VIGOR trial ran for one year: the group of 4000 taking VIOXX had 46 heart attacks, those taking the other drug had twenty. In addition, there were three more heart attacks that occured shortly after the end of the year, all in the VIOXX group: they weren't menioned in the published article, although at least some of the authors were aware of them.
The risk was particularly increased for peope with a history of heart problems: for them, a factor of five increase.
The difference is statistically significant, and has been confirmed: every study since that time had shown similar results.
The idea that the difference might be explained by a cardioprotective effect of naproxen is bullshit. If naproxen had been a strong-enough inhibitor of heart attacks to explain the observed difference, it would have been the most valuable drug on the market.
There is statistically strong-enough evidence that VIOXX increases heart atatck riskm but there is no strong evidence that naproxen hsa any protective effect. One cannot logically use weak statistical evdence to wash away strong statistical evidence.
So don't try.
There is a suspected mechanism: turns that aspirin inhibits platelet clotting (the only known protective effect) - and in inhibiting both COX-1 and COX-2, it inhibits a prothrombotic and an anti-thrombotic enzyme, thus not disturbing the balance. Selective COX-2 inhibitors inhibit only the antithrombotic enzyme. We would have to kill a whole of people with VIOXX to elucidate this mechanism beyond a shadow of a doubnt: I'm for it, as long as I get to pick the subjcts. I have a little list.
Next, a comment or on numbers. Let us assume that the added risk is 26 heart attacks per 4000 per year (from the 1-year VIGOR study): if 35% of those heart attacks are fatal, then the added risk of death is a bit over 2 x 10-3 per year (and there is reason to think that risk goes up with time -worst risk is after 18 months of use. )
Over the year 2003, something like 20,000,000 people - that's twenty million - were taking VIOXX. With that added risk, we're talking 45,500 extra deaths.
That would be bad.
By the way, Merck did _not_ put the strongest possible warning label on Vioxx: the strongest label would have banned high dosages. That did not happen. The label they actually put had no effect at all on dosages used: about 17% of patients used the high dosages before and after the label change. A hint to the libertarians: most physicians aren't up to judging drug safety, let alone John Q. Public.
You evidently misunderstand the notion of giving the benefit of the doubt. We don't need to know the exact mechanism by which Vioxx increased patient risk: we need know only that there was clear evidence of such risk and that merck did not act properly on that evidence. Drugs don't get the benefit of the doubt - people do.
By your argument, we would have had to let Lucretia Boregia loose because we didn't yet understand the biochemical basis of digitalis toxicity.
I'm afraid you are mistaken on almost every point: on points of fact, on your understanding of what a risk level means when applied to million of peoplle, and indeed of the law.
If all you say is true, how is Merck winning these cases in pro-plaintiff counties with pro-plaintiff judges, may I ask?
Mistaken about the law, Mr. Cochran? Are you suggesting Plaintiffs don't need to prove their case? In every products liability case the Defendant has the burden of proof?
However, VIGOR did not result in significant increase in mortality. Those who had CV issues were already high-risk patients for heart trouble. These high-risk patients don't represent 20,000,000 (that's twenty million) users of Vioxx.
Obviously, I am suggesting that a new drug must be shown to be safe, and does not get 'the benefit of the doubt'. I've heard people argue otherwise, but then I've heard a lawyer argue that a ban on pitbulls was unconstitutional breedal discrimination.
There has to be known risk before there can be criminal negligence, but the workings of that risk need not be completely understood. It was silly of you to suggest otherwise.
Merck will get the benefit of the doubt, but it probably won't save them: there's not much doubt. They knew there was a big safety problem, and they [some of them] actively hid it for four years.
As for the three cases thus far, all have been relatively weak: all involved people who hadn't taken VIOXX for more than a couple of months.
But there are plenty of better cases, and I figure Merck is likely to lose them on the merits. Thousands of cases in New Jersey alone.
Are you arguing that the results of a jury trial should be a guide to the truth in a complex technical question? Because that would be funny, as well as silly.
By the way, I freely admit that Greg Cochran knows a heck of a lot more about this than I do.
David Rosenber is a professor at Harvard Law School and probably one of four or five honest and competent legal scholars in all of academia. (He made the news a few years ago for running afoul of the feminists and the "race-doesn't-exist-but-we-need-affirmative-action" crowd.) He has written about these issues of mass torts, probabilistic harm, and so on for the last twenty years. And before that he was the represented the plaintiff in the one of the first cases of this kind (DES). If you have access to Lexis or Westlaw, you might want to check out his scholarship.
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