Sunday, February 19, 2006

The involvement of journal editors in legal cases: Vioxx

Although the journal Science accepted Hwang's 2005 manuscript in a matter of weeks, without presenting objections (even though Hwang did not even have any data on patient specific cell lines), the saga of Merck's submission on Vioxx to the New England Journal of Medicine seems a bit more complicated. You have probably heard of the dangers of the -- track changes -- feature of Microsoft's Word wordprocessor (among other places discussed on IPBiz); the Vioxx case illustrates how dangerous this feature can be to the submitter of the digital version of a Word document. The Vioxx case also may foreshadow a new era in which editors of journals who publish problematic articles can expect to be hauled into court.

Merck prevailed in this particular federal jury trial. Is the journal editor ready to participate in future trials?

Forbes: On Feb. 17, 2006, a jury of five men and three women agreed that Vioxx did not cause the 2001 heart attack death of Richard "Dicky" Irvin, a 53-year-old manager of a St. Augustine, Fla.-based seafood distributor. The case was brought by his widow, Evelyn Irvin Plunkett. The case, which had previously ended in a hung jury in a Houston court, was heard by Judge Eldon Fallon in the U.S. District Court of the Easter District of Louisiana in New Orleans.

"This is a satisfying jury verdict for Merck," said Kenneth C. Frazier, senior vice president and general counsel of Merck in a prepared statement. "Juries in federal and state courts have now rejected unfounded theories about short-term use of Vioxx, and have decided the company acted responsibly in properly disclosing data to the FDA and the medical community."

Plaintiffs' lawyers said they would continue to press on with other cases. Beasley Allen's Andy Birchfield, who represented the Irvin family, said in a statement, "Unfortunately, the testimony by Dr. Gregory Curfman, editor of The New England Journal of Medicine, Dr. Eric Topol, and others was apparently not enough to convince the jury that Vioxx caused the death of Dicky Irvin." He added, "We are determined to go forward on behalf of other victims of Vioxx. Merck intends to fight each and every Vioxx lawsuit and so do we."

from AP on Feb. 10, 2006: The New England Journal of Medicine demanded changes before publishing results of the study that led Merck and Co. to pull the painkiller Vioxx from the market, and one of its top editors disputes the way the drugmaker is using it as a pillar of its legal defense in liability suits.

According to a court deposition of Executive Editor Gregory Curfman, the respected medical journal initially didn't accept the draft of the manuscript because it advanced the idea that Vioxx use was safe for up to 18 months. Curfman said he contested that claim.

Such editor-author discussions are commonplace, but this disagreement goes to the heart of Merck's defense: The company contends that a doubling of risks for heart attacks and strokes didn't show up until after 18 months among users of the pain medication, and that once those findings became known, the drug was immediately pulled from the market in September 2004.

from "in the pipeline" on Jan. 23, 2006:

Tuesday and Wednesday of this week are the days when Merck's attorneys are scheduled to question Dr. Gregory Curfman of the New England Journal of Medicine and another unnamed staffer. The journal's handling of the published Vioxx data (the VIGOR study) looks as if it could be a key part of the next trial, which will be in lawsuit-friendly Rio Grande City, Texas, with jury selection beginning this week. Note that the late plaintiff had taken Vioxx for all of seventeen days.

The Jan. 23 post references a Dec. 13 post:

Why did the New England Journal of Medicine come out with their "expression of concern" last Friday?

Then the first Federal case starts up, and the journal's editor is brought in to give a deposition. And now the editorial staff springs into action, rushing out an unprecedented comment on a paper from their own journal that manages to publish on a Friday afternoon. All of a sudden, somehow, things couldn't wait.

Could it be that the plaintiff's attorneys, while questioning Gregory Curfman, mentioned that there could be more targets for litigation than just Merck? You run a prestigious journal there. . .probably influenced a lot of physicians to prescribe Vioxx, eh? Didn't see anything odd in the cardiovascular data, you say? Why, that's nearly a tort right there. . . I don't like to think that this is what happened. But it's not impossible, either. The journal's actions look like those of an organization that fears the legal discovery process. And why would you fear that, unless you fear that you'll be sued?

from "in the pipeline" on Dec. 9, 2005:

You don't see many articles in the medical literature titled "Expression of Concern". But that's how yesterday's release from the New England Journal of Medicine starts out (PDF).

The editors are expressing their concern over the published VIGOR trial data from 2000. It turns out that some time ago, the journal's editors had found a disk which had been part of the submission of the paper, and it contained earlier versions of the manscript. These had a blank table for cardiovascular events, and in what looks like another example of the wonders of the "track editing changes" function, it appeared that the table had been deleted by Merck two days before the final version. The journal wasn't sure what to make of this, and kept quiet (for four years) until their editor, Dr. Gregory Curfman, went through a deposition during this latest trial. He then saw a complete version of the earlier manuscript, which seemed to show more adverse cardiovascular data than appears in the final published version. (Forbes is all over this story; check that link for the full details).

One comment-->
I think it is irresponsible for NEJM to come out with this. I would regard pre-press communications between journals and authors to be confidential, unless subpeoned. This SERIOUSLY undermines my faith in NEJM's ethics.

A different comment-->
There are any number of changes that a manuscript could go through prior to submission for any number of reasons. I've been known to put "fake" data into a manuscript in progress just as a placeholder to work out formatting, for example. Or to write in throw-away notes for sections I don't want to work on right away, such as "discuss BS paper by Smith et al. and why it's wrong". All of which could be greatly misconstrued by someone--especially someone with an agenda.

A different comment -->
I think it's perfectly legit to go delving into the documents you've been sent, particularly if questions of malfeasance are on the table. The Jan-Hendrik Schon scandal was definitively proven through such means. [IPBiz note: Huh?] I don't think the NEJM can be faulted for this. But...

[IPBiz note: Both the Schon and Hwang frauds were uncovered through the actions of INSIDERS contacting THIRD PARTIES.]

A different comment -->
In my view, the original NEJM article does everything possible to downplay the cardiovascular risk of Vioxx, short of lying. There's no table of cardiovascular risk data, only discussion in the text. Results are reported as reductions in MI due to Naproxen, not increases due to Vioxx. There's speculation that the results are due to the cardioprotective effects of Naproxen (unsupported at the time, and since debunked -- Naproxen may be somewhat cardioprotective, but not nearly enough to explain a 400% difference in MIs). Finally, there's the implication that the problem isn't Vioxx, it's that patients weren't taking aspirin. But aspirin isn't remotely protective enough to offset a 400% increase in risk. So, I'm not surprised that the NEJM editors feel like they've been misled.

[IPBiz post 1251]


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