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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

« Everything's Under Control, Right? | Main | No More Merck For A Couple of Days »

August 19, 2005

Judgement Day

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Posted by Derek

A during-the-working day update, and I don't think I've ever done that for good news. Merck has been found liable in the first Vioxx trial. The jury has awarded 24 million dollars in outright damages, and $229 million in punitive damages. (If you'd like a strictly utilitarian, economic response to that award, start by pricing out what $253 million dollars of life insurance will cost - that is, if you can get anyone to not hang up the phone on you.) Merck, of course, is going to appeal.

It shouldn't be any surprise to find out that I think that this is terrible news. While I think Merck really pushed Vioxx too hard, as have the other companies with COX-2 inhibitors, I don't see a way to justify that large an award. This might open the door to a number of such awards, and Merck could end up spending its money fighting for its life rather than trying to bring new drugs to market. Enough of these losses, followed by losses on appeal, could sink the company completely.

I know, I know. They should have thought about that before flogging Vioxx to everyone that could bend their finger joints, right, right. But if every new drug we take to market is going to have a reasonable chance of ruining the company, why bother? And I know the answer to that one, too: "just make sure they're safe." What tiny words "sure" and "safe" are. You wouldn't think that they could cause the trouble that they do.

Comments (18) + TrackBacks (0) | Category: Current Events


COMMENTS

1. Linkmeister on August 19, 2005 4:18 PM writes...

But the usual pattern is that the huge (Page A1) awards get knocked down by the judge, and that's buried on page A31. I'd expect that to happen this time, even if the appeal fails.

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2. John O'Donnell on August 19, 2005 4:29 PM writes...

This makes it pointless to invest in any drug company or healthcare in general. No science can provide the kind of guarantees the system seems to demand within the patent window. I have about 15MM in healthcare.... until Monday. CYA.... it's like the jury thinks they were MO or something.... completely stupid

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3. Jim on August 19, 2005 6:33 PM writes...

In Texas (where the trial was held), punitive dmgs are capped at twice the economic damage. So with the economic dmg, mental anguish, and the capped punitive, the award amt will not exceed $26.1 million for this case.

Still, a $229 mil. punitive dmg award is completely insane...

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4. Patrick on August 20, 2005 2:50 AM writes...

This is insane. I begin to agree with Pfizer CEO Hank McKinnell's suggestion in his new book that a specialized court system like military tribunal being set up for healthcare suits like malpractice and this one. There's just too much professional knowledge and circumstances involved that it's too difficult for the average jurors to comprehend the things in such a short time period. Maybe it's just too difficult to let average citizens understand the scientific uncertainty related to every drug product. We have very few other products with characteristics of drugs on this planet.

Unlike other industries, there is a FDA hanging upon on all pharma companies. The Vioxx thing should be shared responsibilities. While the society needs lawyers in general, however, when they smell blood they are playing zero sum game to the society. It’s too bad.

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5. Tom Womack on August 20, 2005 10:21 AM writes...

$250 million is clearly a crazy amount to give as punitive damages from a single case, if it is to be considered precedent for all other such cases.

I'd tend to argue that the large capital loss from having developed production equipment and paid for copious marketting for a drug that turns out sometimes to be harmful, and therefore will sell very poorly, is probably enough (indeed, possibly more than enough) punishment to a company for the simple fact of having missed a rare side-effect in clinical testing. It may be Merck is liable to the tune of some few billions of dollars for the cost of treating the side-effect, but that's actual rather than punitive damage.

On the other hand, Merck does seem to have concealed information about observed dangers of the drug; that's corporate malpractice, and hundreds of millions of dollars appears (see Eliot Spitzer passim) to be the sort of level of fine that large-scale corporate malpractice involves.

So I'd say the situation was pretty much reasonable, provided that the legal outcome is that, having paid the punitive damage in this case, Merck is adequately punished and will not have punitive damages levied against it in any other case. The way I gather the US legal system works, this is not the outcome that will occur.

I'd prefer the punitive damage to have been paid to the government rather than to the plaintiff's lawyer, but that's just my inner socialist speaking; besides, whilst in the UK it's obvious that the punitive damage would be owed to the NHS, it's not at all clear which bit of which level of the government should get the money.

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6. WBurke on August 20, 2005 11:50 AM writes...

Wow!!! Hey listen Derek, I know the verdict has to have hurt, and I'm sure Merck didn't mean for anything bad to happen to anyone as they are only interested in helping people (yeah RIGHT!!!).


What a start to what is sure to be a painful if not terminal litigious season for Merck. I like the thought of safe and effective therapies, that is why I choose the best preventive measures possible (effective nutritional supplementation and a healthy diet - note that is a non-ADA, AHA diet) and when seeking help in the realm of cancer (an area you discuss in a newer posting) I agree with you that there should be a broader base of application sought for in therapies, hey maybe now you can get behind the cure for cancer Dr. Rath developed and help bring it to a broader market by raising awareness in the medical community, I'm sure since they are searhcing for a cure they would be happy to lend a hand financially and vocally, right?

I mean they do want to find a cure, right?

And if there were one out there they would promote it right?

I mean don't tell me the whole "Run for a cure!" "Race for a Cure!", "Drive for a cure!" Susan G. Komen/American Cancer Society efforts to find a cure are phony and illegitimate pleas to simply separate people from more of their money are they?

Hey look at the whole Vioxx Trial things like this - 1 down, 150,000 to go!!! :-)))

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7. tgibbs on August 20, 2005 5:08 PM writes...

I'm not convinced that Merck did anything improper. I suppose that red flags might have gone up a bit earlier--Merck's initial presumption that the excess of cardiovascular events in the trial against naproxyn was due to a protective effect of naproxyn seems like wishful thinking, particularly in the light of more recent data suggesting that naproxyn itself may carry a cardiovascular risk. But hindsight is easy. Some of the articles I've seen that indict Merck based on reanalysis of old data seem to be to be committing the sin of after-the-fact statistics: it is a lot easier to find significance when you already know the answer.

Did Merck overpromote Vioxx? Maybe, but NSAIDs in general carry a significant risk from bleeding, so Merck perhaps can be excused for imagining that COX-2 inhibitors such as Vioxx would be safer overall. Indeed, it is still not clear to me how Vioxx shapes up when the risks of the alternatives are fully factored in. If ibuprofen carries a little less cardiovascular risk and a little more bleeding risk the Vioxx, is it really safer overall?

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8. Derek Lowe on August 20, 2005 6:45 PM writes...

Mr. Burke, you act as if no one who does cancer research ever gets cancer or has any friends or relatives that do. I can tell you from personal - very, very personal - experience that you are incorrect. Your suggestions are beneath contempt. Keep making them, and I will ban you from this site, at long last.

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9. WBurke on August 20, 2005 10:15 PM writes...

Go ahead and ban me Derek, if you can't handle the truth resort to shutting off the voices of it. That is the route you scum usually resort to.

An idea goes through 3 stages - first it is ridiculed - you've been doing that one for I don't know how long but it exceeds the time I've known you I'm sure.

Secondly it is ignored. You've revealed you can do that and will resort to shutting up the only voice of reason in your world of strawmen and yes men.

But when cancer hits your body you will be forced to recognize the very real fact that you've chosen the wrong side of the issue and the 3rd stage will smack you in the face which is that it becomes self-evident.

So whatever you do Derek I really couldn't care less - I'm done here anyway.


Go ahead breathe your sigh of relief.

Permalink to Comment

10. Richard on August 21, 2005 6:59 AM writes...

Low dose aspirin (a COX-1 and COX-2 inhibitor) is well known to reduce heart attacks by interfering with clotting (via platelet activation).
The unfortunate side-effect is bleeding!


Vioxx by being a specific inhibitor of COX-2 stops the bleeding risk, but by not interfering with the platelets means clots (that may block an important coronary artery) aren't dispatched as they would be.


I can't see any obvious reason mechanistically why Cox-2 inihibitors would increase cardiovascular risk by themselves other than these patients aren't getting the cardio-protection of COX-1 inhibition


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11. PsychicChemist on August 21, 2005 10:38 AM writes...

I should try to dif up E.J. Corey's paper from a recent issue of Tet Letters as to why Vioxx is toxic but the other Cox-2 inhibitors are not. I think they also mention in the acknowledgements that EJ consults for Pfizer. The fact that he would publish this in Tet Letters (the editor Bruce Ganem is his nephew)tells me what his theory is worth. Despite that the paper made it to C&E news.

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12. Kay on August 21, 2005 12:11 PM writes...

Perfect example of how payola in pharma marketing comes back to roost. Payola has certainly helped decrease the stature of physicians and pharma.

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13. Matt on August 21, 2005 2:52 PM writes...

"But if every new drug we take to market is going to have a reasonable chance of ruining the company, why bother? And I know the answer to that one, too: "just make sure they're safe." What tiny words "sure" and "safe" are. You wouldn't think that they could cause the trouble that they do."

I don't think "safe" was what was argued. I believe the problem wasn't whether it was "safe" or not, it was whether Merck fully disclosed the risk.

Permalink to Comment

14. tgibbs on August 21, 2005 3:21 PM writes...

I can't see any obvious reason mechanistically why Cox-2 inihibitors would increase cardiovascular risk by themselves other than these patients aren't getting the cardio-protection of COX-1 inhibition

This was clearly what Merck thought. The problem with this sort of neat hypothesis is that after a while, it can become a kind of mechanistic "just so story," and it is easy to forget just how complicated biology can be. The apparent protective effect of naproxyn in Merck's study was higher than expected, but they hadn't seen cardiovascular problems with Vioxx in other, short term, studies, and you know: different patient populations, statistical variation.... What the later data suggest, however, is that there is probably a cardiovascular protective effect of COX-2. With nonselective NSAIDS, the detrimental effect of blocking COX-2 is likely masked to some extent by the protective effect of COX-1 inhibition.

There is a 1999 report that selective COX-2 inhibitors as well as nonselective COX inhibitors decrease urinary excretion of a metabolite of prostacyclin, which is a vasodilator and platelet aggregation inhibitor, although the importance of this effect was unclear at the time. This makes prostacyclin a plausible candidate for a protective substance produced by COX-2, but I don't know if there is any additional data to confirm this speculation.

Of course, this is Monday-morning quarterbacking. Merck didn't really believe that the data demonstrated a risk for Vioxx, but just to be sure, they decided to examine its cardiovascular risk in study of a potential anticancer effect of Vioxx, which had a proper control, and it was the early results of this study that led Merck to yank Vioxx. In hindsight, they probably made the wrong call by waiting, but keep in mind that a drug like Vioxx could have been saving lives by reducing the risk of bleeding, so they could kill people by being too quick on the trigger, too. I don't know if anybody has done any study looking at all outcomes that would really tell us if Vioxx was doing more harm than good.

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15. steve on August 21, 2005 8:54 PM writes...

It really bothers me that everyone shrugs at the lack of accounting for reduced bleeding deaths, and that no one compares the equivocal information available about "safe" drugs at the same stage as the "dangerous" ones.

This is reminiscent of those "strike suits" (before the law restricting them) where every time a stock went down after a new product flopped, company archives would be ransacked in discovery to find some pre-launch warning memos that the product might not be a good idea. I once asked an expert witness for the defense whether anyone ever bothered to look at successful products and show that the same kinds of memos were floating around there, too. He replied in the negative.

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16. Reuben on August 22, 2005 10:19 AM writes...

Hi Derek,

Don't you think Merck would appeal, even if the jury awarded 'just' say about $ 10 mil.? Merck has no other options than to fight this case as if its life depends upon it(it does!). The real issue here is not Merck and other pharma's being money sucking maggots, by promoting poorly tested drugs on joe schmo!, but testing requirements and results that are difficult to interpret and replicate. An answer may be found in involving a much more sophistcated mathematical modeling framework and algorithm design in clinical trials.

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17. Tom Bartlett on August 22, 2005 11:59 AM writes...

"In hindsight, they probably made the wrong call by waiting, but keep in mind that a drug like Vioxx could have been saving lives by reducing the risk of bleeding, so they could kill people by being too quick on the trigger, too."

Vioxx helped a lot of RA/OA patients walk without pain. It is irresponsible to "pull" what is clearly a pretty safe drug without carefully looking deeply at the data.

I hope on appeal, Merck wins this case outright. Woe to Pharma if this kind of know-nothing attack is allowed to stand.

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18. simon on August 22, 2005 9:03 PM writes...

The decision is a very sad one ... it shows a poor understanding of science and risk ... and more seriously potentially undermines our economy ... no treatment is perfect and without risk ... the problem that we are confronted with is a legal definition that does not reflect the probabilistic world we live in ... The laws must be changed to reflect probabilistic reasoning which humanity has developed since Pascal ... judges and law makers must be trained in probability ... I would place this as the MOST important action for our millennium ... it is probably the hardest

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