Talk:Rofecoxib

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[edit] Style of reference to Lancet publication

I think the reader is better off with a clickable hyperlink right at the point where information is stated. Changing the Wikipedia article to the more conventional scientific format means that a reader who's interested in this article's summary of the meta-analysis, and wants to read the original, has to note the lead author's name and then find it in the "References" (perhaps after looking in vain in "External links", where such things would be in most Wikipedia articles). Nevertheless, I don't usually edit scientific articles, so I'm not going to take on a battle over whether we should follow the style guides that evolved before anyone had heard of a hyperlink.

One point has to be made clear, though. Jüni et al. did not make the criticism of the FDA. The Lancet published their study and also offered a "Comment" expressing an editorial opinion. That opinion must be separately cited so as not to be imputed to the named authors. I've restored an inline hyperlink to [1] (different from the Jüni et al. paper, which is at [2]). An editorial seems to me to be an even worse candidate for the conventional citation of a research paper. If it were to be transformed, though, I suppose it would be "(Horton, 2004)" in text, and a "References" listing of:

I'd oppose presenting it this way but, there, I've done the work if that's the format scientific editors insist on. (I've done my best, anyway. I don't know the rules for this format. Does a comma separate an author's surname from his or her initial? There's a comma at that point in Senator Grassley's listing but in no others.) JamesMLane 07:34, 10 Nov 2004 (UTC)

I was following the recommended APA citation style recommended on the Wikipedia cite sources page, mainly to make it flow a bit better. Of course there is no absolute style to follow, so I won't edit what you've done with the editorial comment for the time being. Some people in the scientific field can get really anal about citation styles; but I think it's really whatever style is consistent to what's already on the page and whatever flows (e.g. you wouldn't really want an entire article interspersed with external links - but neither would you really want (Foobar, 2004) every sentence either. Either way, it's still probably a good idea to have a formalised reference section at the bottom. With the editorial thing, it was my mistake changing that, since I wasn't able to access that editorial and I'd assumed that the link pointed to merely a print version of the online article. Thanks for changing it back to reflect what it was really meant to say. Techelf 07:54, 10 Nov 2004 (UTC)
For my part, I wouldn't mind at all having an entire article interspersed with hyperlinks. It would address the main criticism of Wikipedia -- that you can't trust the content. In fact, with the benefit of hindsight, I'd say that, beginning with the creation of Wikipedia, requiring the inclusion of a link or an offline reference for each assertion might've been a good idea. Anyway, as to the format, I'm in no position to criticize people who get anal about APA style. I've done the same on law-related articles with passages that don't follow proper legal citation style. JamesMLane 08:15, 10 Nov 2004 (UTC)

[edit] Litigation: cap on punitive damage

in the litigation chapter it is written 'but this will likely be cut to no more than USD$26.1 million due to the cap on punitive damages under Texan law'. I found a similar line in The New York Times. Kind of astonishing that the jury awards damages it knows is too high under Texan law. Can somebody explain the nature of this cap? Hppl 21:14, 20 August 2005 (UTC)

The reason this occurs is to "send a message" to the losers. In fact, the gross majority of damage claims that are above a few thousand dollars will be diminished to some degree after the initial verdict.

Caps on punitive damages are usually installed to prevent a "jackpot" victory, where the first person to win a lawsuit against a mass-tortfeasor would extract all they money from the tortfeasor. With these caps, in theory at least, multiple victims can seek reasonable compensation.

[edit] SMILES string?

Can anyone explain why we need a SMILES string here when there's already the molecular formula and structure? -Techelf 09:49, 23 September 2005 (UTC)

[edit] Drug Prohibition and Vioxx

Techelf, please think before you revert next time. I merely posted a widely held opinion which is commonly argued in anti-prohibition/Libertarian/Harm reduction/ chronic pain patient circles. I posted this in a paragraph where two other political opinions were already present, and clearly stated that this was just another opinion held by some people. ...and you come along to erase my work, claiming it was 'POV'. Brilliant, Techelf. The entire purpose of the paragraph was to document various political opinions regarding the vioxx scandal. I just added one more. Not to mention that it is an undeniable fact that millions of pain patients were given vioxx when they would have preferred opioid medication. Nevertheless, I'll be willing to accept your apology. Rearden Metal 23:08, 15 February 2006 (UTC)

Calm down, mate. Firstly, you should not be so presumptuous as to expect an apology from me or anyone else on Wikipedia. This is not your article – Wikipedia involves a collaboration of people including patient-advocates, such as yourself, and healthcare professionals such as me. Therefore, I hope you understand that I reverted your edits because I disagree with your implication that physicians should prescribe based on what patients "prefer". Neither should physicians prescribe based on fears in a litigation-friendly and prohibitionist political environment that may exist in the U.S. If this is, indeed, occurring then it would be useful if you could cite a reliable reference. I do admit that I was somewhat hasty in reverting your edits, without fully understanding your intended meaning. However, I'm more than happy to discuss this issue with you here in a professional manner, so let's just resolve our differences and work together. -Techelf 08:38, 16 February 2006 (UTC)

Hi again, mate. I'd say you handled that pretty well this time. I wasn't really expecting an apology ;). The vioxx scandal is just one way in which the War on Drugs has claimed thousands of innocent lives. Here's a piece by the Cato Institute:

http://www.cato.org/pub_display.php?pub_id=3778

More evidence:

http://www.cbsnews.com/stories/2005/10/25/opinion/main975946.shtml

http://www.house.gov/paul/tst/tst2004/tst051704.htm

http://www.aapsonline.org/press/hurwitz1002.htm

I agree that resolving our differences and working in a professional manner would be best. Rearden Metal 22:49, 16 February 2006 (UTC)

Claims that drug prohibition greatly amplified the vioxx damage may not be a focus of Hannity or Limbaugh- but this is indeed common knowledge in anti-prohibition/Libertarian/Harm reduction/ chronic pain patient circles.

http://www.drugwar.com/pjudyhall.shtm http://www.hempworld.com/MarijuanaStore/html/govt_is_our_enemy.html http://www.compassionatecoalition.org/phpBB2/viewtopic.php?p=8288&sid=1510d7515cb4c490d498486c9ab7e2f6 http://stopthedrugwar.org/chronicle/368/disinfo.shtml http://www.ccrmg.org/chrono.html http://www.november.org/stayinfo/breaking3/ScaryDrugs.html http://www.alternativesmagazine.com/33/bayer.html http://www.guerrillanews.com/articles/1500/The_Vice_Lords_of_the_Replacement_Economies http://nobodysbusiness.typepad.com/nobodys_business/2004/12/fear_your_docto.html http://www.newmediaexplorer.org/sepp/2005/06/07/medical_marijuana_us_supreme_court_upholds_federal_prohibition.htm http://www.cannabisnews.com/news/thread20073.shtml

It isn't some crazy theory I cooked up, and I could easily provide hundreds more articles explaining how the prohibition laws were a direct cause of many (if not most) of the vioxx deaths. This is a significant viewpoint, held by many, and clearly belongs in the Political impact of Vioxx litigation in America section. Rearden Metal 05:37, 23 February 2006 (UTC)

Aside from the fact that none of these sources are credible, the first two I checked said nothing about Vioxx litigation. Add a different section if you want to talk about this issue, but keep it out of Vioxx litigation.
By the way, I happen to agree that the government overregulates Oxycontin. But it has nothing to do with Vioxx litigation.

I seem to be the only Wikipedia contributor here to see the direct connection between drug prohibition, government oppression of those physicians who are 'too generous' with narcotic analgesic scripts, and the damage thereby caused by the vioxx commonly prescribed as an ineffective and often lethal substitute. I'm not going to keep trying to force such a widely unpopular addition into this article. I'm waving the white flag on this one. Rearden Metal 22:23, 23 February 2006 (UTC)

[edit] VIGOR, naproxen, and NEJM editorial

I have reverted 69.143.115.175's edits for the reasons discussed below.

69.143.115.175 writes (in italics):

Merck's scientists interpreted the finding as a protective effect of naproxen. Some commentators, however, have noted that this would make naproxen three times as effective as aspirin), and no evidence has since emerged for such a large cardioprotective effect of naproxen (Karha and Topol, 2004). Merck never argued that naproxen was three times as effective as aspirin, merely that a minor cardioprotective effect for naproxen would explain the statistical significance of the difference of the results, and would be consistent with a larger studies showing no additional cardiovascular events for rofecoxib usage. (Konstam et al., 2001.) Other studies have since shown that naproxen does have a cardioprotective effect. (E.g., Solomon et al., 2002.) Though Dr. Topol's 2004 paper criticized Merck's naproxen hypothesis, he himself co-authored a 2001 JAMA article stating "because of the evidence for an antiplatelet effect of naproxen, it is difficult to assess whether the difference in cardiovascular event rates in VIGOR was due to a benefit from naproxen or to a prothrombotic effect from rofecoxib." (Mukherjee, Nissen and Topol, 2001.)


Ragout 06:52, 9 March 2006 (UTC) replies:

First, this is incoherent ("statistical significance of the difference of the results" means what?). Second, Merck certainly has argued that naproxen was 3 times as effective as aspirin. Merck claimed that the cardioprotective properties of naproxen explained the 80% difference in MIs. Since aspirin reduces MIs by perhaps 25%, the 3 times claim follows. Third, the studies discussed in Konstam et al are not "larger." They are smaller. Fourth, this section is about VIGOR; I don't think other studies should be discussed here. Fifth, the Topol quote is misleading. In context, it is clear that Topol is making a concession for the sake of argument. In that paper, despite the concession that "it is difficult to assess" which drug caused the difference in MIs, Topol goes on to assess precisely this, and concludes that rofecoxib is to blame. Quoting Topol out of context like this is blatent bias.

If you don't know what "statistical significance of the difference of the results" mean, you have no basis to claim that the edit is incorrect. Merck never claimed that naproxen fully explained the 80% difference, merely that it explained the statistically significant part of the difference.
If, as you acknowledge is possibly the case, naproxen has the same (or even less of a) cardioprotective effect than aspirin, then the null hypothesis "VIGOR's difference in cardiovascular events between rofecoxib patients and naproxen patients can be explained by naproxen's cardioprotective effects" is consistent with the statistical significance of the results. Arguing that naproxen has to be "three times more cardioprotective" is only true if Merck sought to claim that the entirety of the difference, rather than the statistically significant portion of the difference, from VIGOR was due to naproxen. But Merck never made the former argument: it argued that naproxen explained some of the difference, and the rest was within normal statistical variation. And that argument is entirely consistent with the data; the only reason the FDA rejected the argument and required a warning-label change was because the FDA does not permit pharmas to claim a cardioprotective effect for naproxen in advertising. Topol's argument is a statistically-illiterate (or, more likely, simply disingenuous) strawman. If one is to include it, one must include the entirety of the context.
I don't know what "explain the statistical significance of the difference of the results" means because it is meaningless. You do Merck no favors by attributing such nonsensical statements to them. Your explanation above is even worse. The "statistically significant portion of the difference"? Statistical significance is a yes/no concept: there are no "portions." I am tempted to leave your statement alone, but that would not be fair to Merck. If you have some reference where Merck said anything vaguely like this, please post it. I do not believe that Merck ever made such a claim.
It does seem likely that Merck claimed a "minor cardioprotective effect" for naproxen, since this is a reasonable claim, but as far as I know they have never done so. I note that you provide no reference to such a statement by Merck. In any event, it is demonstrably false that Merck "never argued that naproxen was three times as effective as aspirin." They did so in Bombardier et al. Also, they told the FDA "the difference in myocardial infarctions between the two groups [in VIGOR] is primarily due to the antiplatelet effects of naproxen." See this FDA Memo, page 34. I am going to edit out "minor," etc., and write something about "primarily." Ragout 01:25, 10 March 2006 (UTC)
I've restored Topol's 2001 statement. If you wish to add additional language or delete it entirely, I'll accede to that decision. But it's untrue that Topol concludes that rofecoxib is to blame in 2001; rather, he identifies it as a possibility and calls for more study. Which is consistent with the quote I gave.

69.143.115.175 writes (in italics)

Months after the study was published in the New England Journal of Medicine, the journal editors learned that the authors had not reported certain data in the article; years later, in the midst of deliberations of the first federal Vioxx trial, the editors wrote an editorial accusing the authors of deliberately withholding the data (Curfman et al, 2006). The editors charged that "more than four months before the article was published, at least two of its authors were aware of critical data on an array of adverse cardiovascular events that were not included in the VIGOR article." The authors of the study, including the non-Merck authors, responded by claiming that the additional adverse events had occurred after the cutoff date for data collection and thus were not appropriately included, that the data did not change the conclusions of the study and were not statistically significant, and that the additional events were disclosed to the FDA and the public. (Bombardier et al., 2006). Many scientists have accused the NEJM editorial board of playing politics and making inappropriate accusations.

Ragout 06:52, 9 March 2006 (UTC) replies:

I do not believe that any scientists have accused the NEJM of "playing politics" (whatever that means). The provided link does not back up this claim.

The rest of this is simply Merck's spin, not NPOV. It suggests (following Merck's line) that the only issue was with 3 adverse events after the cutoff date. But in fact, the NEJM editors had other objections as well. The editors did not learn of the additional data "months later." They only learned of the 3 MIs at that time. Note that most of this paragraph discusses Merck's response & spin. It doesn't make clear the editor's objections to the exclusion of data on other adverse outcomes besides MIs.

WP:NPOV means both points of views. It doesn't mean that the author gets to choose which point of view he thinks is right. You may be right. But because it's disputed, both sides get their say.
Indeed both point of views should be in the article. The problem is that you have edited out one of the NEJM editor's two criticisms of Merck. They criticized Merck both for not reporting the 3 MIs and for not reporting a large amount of other data. That is the point of the "supplementary material" in the NEJM editorial. I am adding back this other criticism. Ragout 01:25, 10 March 2006 (UTC)
The editors did learn of the omitted data months later, because Merck disclosed the omitted data publicly. And they say as much in the editorial -- see Curfman et al., which complains only of CV events. It's also worth noting that the non-Merck authors of the study come to the same conclusion as the Merck authors of the study. This isn't just Merck spin, it's also the conclusion of several disinterested observers, including Lowe, who found the NEJM editorial was tremendously unfair, and argues that scientists will stay away from NEJM in the future.
You seem to be right that the omitted data was available a few months later. However, by omitting the NEJM editors explanation of why they did not act for several years, your text insinuates that they did something underhanded. I am adding their explanation Ragout 01:25, 10 March 2006 (UTC)
I think "playing politics" is a fair characterization given Lowe's harsh criticism (and those of his commenters), the timing and Curfman's subsequent cooperation with plaintiffs' attorneys, but I've changed the characterization to reflect your concerns. I've also added a reference to the reaffirmation of the editorial.
I've moved this discussion to the bottom of the talk page, pursuant to Wikipedia convention. Please read the FAQ. -- 69.143.115.175 14:22, 9 March 2006 (UTC)

[edit] March 17 edits

1) The AP/Forbes article cited explicitly says Curfman didn't testify in December.

The article says he didn't testify on a certain day in December, not that he never testified. You may well be right that his deposition testimony was never played to the jury, but it's important to clarify that he had been deposed long before the NEJM editorial. This undercuts any implication that he was trying to influence the trial by publishing the editorial. Ragout 05:26, 18 March 2006 (UTC)

2) The Yale cardiologist didn't just volunteer his dislike for VIGOR, he was paid to do so as a testifying expert. It makes a difference.

I can hardly deny that. Indeed, there's a lot of information that bears on the scientists' credibility that's relevant to this paragragh. It's just that you deleted the info contrary to Merck's position that I added (Lowe's pharmaceutical industry ties, Topol's awesome publication record). Anyway, instead of adding this and other relevant info, I'll just replace Krumholz with the editor of JAMA. It's not like there's a shortage of prominent scientists who support the NEJM editorial.

3) The Bloomberg story is wrong. Either Topol got it wrong, or the reporter got it wrong, but the actual Study 090 data does not show a six-fold increase. Looking at the numerators without looking at the denominators is an amateurish error.

I can't believe you'd even consider the idea that Topol, probably the world's best research cardiologist, would make a boneheaded error in his field of expertise. Of course Topol is right. He's simply citing figures that compare rofecoxib to all the controls (both on nabumetone and on placebo). You, on the other hand, are cherry-picking results you like. I think Topol's summary makes more sense, but I'm going to leave the results vs. placebo and add the 7-fold RR vs. nabumetone, and the statistically signficant increase in heart attacks + stroke.

4) Swan is Suzanne K. Swan. She's not Merck's Australian subsidiary.

My mistake. I thought you were putting back in the misleading (Swan 2004) reference to the Swan, Dohme, & Merck corporate press release that I had just corrected.


5) It's bizarre that you identify Patrono's views as "Merck's argument." Even if he occasionally consulted for Merck, Patrono is an academic, not a Merck employee. Further, his views clearly differ from Merck's. In Bombardier et al, Merck scientists claimed the VIGOR "results are consistent with the theory that naproxen has a coronary protective effect." In the memo you cite, Patrono is reported to have said in a private conversation that he "does not think that the CV effect [in VIGOR] can be attributed to naproxen." So Patrono does not speak for Merck, nor does he have the same views as Merck. It would be much more accurate to say that outside experts warned Merck that their naproxen claim was absurd, but Merck ignored them. In fact, let's change the article to say that. Ragout 05:26, 18 March 2006 (UTC)

[edit] removed to lawyer's page

Looks like a self-serving way to drum up business. Let the consensus decideDlohcierekim 01:52, 20 March 2006 (UTC)

PS the url is http://www.vioxx-lawyer-all-about.com/. anon insists I'm mistaken. I shan't rvrt 3rd timeDlohcierekim 02:08, 20 March 2006 (UTC)

[edit] Three elements

The Ragout listing of three elements needed to prove a Vioxx case was both over- and under-inclusive, and just not accurate. (For example: judges so far have only required plaintiffs to prove that Vioxx was a substantial contributing factor, not that Vioxx was the specific cause; if there's a failure-to-warn claim, they need to prove that the failure to warn was a substantial contributing factor.) There are also state-by-state variations that need noting, and the FDA argument that state failure-to-warn law is preempted by an FDA-compliant label needs to be noted if we're going to get into the legal issues. And just about every case has tacked on a consumer-fraud claim. Don't have time to rewrite it now, but I will eventually. -- 69.143.115.175 11:34, 14 April 2006 (UTC)

That's perfectly OK with me (although I might try to incorporate your points if I get a chance). Two comments. 1) To a layperson like me, the distinction between product liability and consumer fraud is uninteresting, since both require that basically the same thing be proved. So I don't think the article should do much more than mention consumer fraud (unless I'm wrong and there's more to the distinction than just the amount of damages that can be awarded). 2) To me, the most interesting legal/philosopical issue is how non-Vioxx risk factors affect specific causation, so I'll probably try to add something about that too.Ragout 14:26, 14 April 2006 (UTC)
NB that consumer fraud is substantially different than the product-liability claim--for example, the Cona jury found for him on the consumer-fraud claim, but not on the product-liability claim. There's also a $12 billion class action pending in New Jersey on the consumer fraud theory. This whole thing may merit breaking out into a separate "Vioxx litigation" article.
Fair enough. Now that you point it out, I certainly don't understand how the Cona jury could have ruled differently on product-liability and consumer fraud. I think my version of the legal issues is no more distorted than the newspaper version, but it sounds like that's not too impressive a claim. Ragout 14:01, 17 April 2006 (UTC)
One has to be impressed with the cleverness of the plaintiffs' bar: if the plaintiff has no risk factors, then they blame Vioxx; if the plaintiff has lots of risk factors, then Vioxx "pushed them off a cliff." But we know that it's not the case that 100% of heart attacks are caused by Vioxx. Interesting article.
I see the irony. Still, from my point of view, Merck should mostly win when there are no other risk factors and mostly lose when there are lots. So I suspect that Lanier won the first case (no risk factors) on good lawyerin, and that plaintiff's lawyers may have lost the next few (mostly many risk factors) because they followed Lanier's strategy too closely. Now justice may be starting to prevail, as plaintiff's lawyers figure out how to argue the "close to the cliff" case.Ragout 14:01, 17 April 2006 (UTC)
The other alternative is just linking to the various product liability articles that already exist in Wikipedia, rather than reproducing it from scratch. product liability; implied warranty, etc. Those articles need a lot of work, too, but cleaner to link to them than to create lots of parallel discussions of legal issues. Cheers. -- 69.143.115.175 02:38, 15 April 2006 (UTC)

[edit] Missing history

This article begins with the story of how the drug was withdrawn from the market. I came here to find out when it was approved for the market. Where is the history of the drug's development and introduction? --Blainster 19:09, 18 May 2006 (UTC)

[edit] Can this really be right?

In the discussion of the NEJM's authors' response, this was stated:

the additional events were disclosed to the FDA and the public on the Vioxx warning label

Now I have not seen the warning label in several years ;), but am wondering if it makes any sense at all to have specific events of one particular study included on the warning label of a bottle of pills. It would be one thing if it were the first time ever these types of events were seen, but these were merely additional events of an already observed type. Should this read something like

the results of the full analyses were disclosed to the FDA and reflected on the Vioxx warning label

? Baccyak4H 15:07, 30 August 2006 (UTC)

[edit] Kent

Could someone change Kent and Co. to Merck & Co? I can't seem to find the edit link for the introduction. —Preceding unsigned comment added by 91.86.17.251 (talk) 21:38, 29 February 2008 (UTC)