As most anyone who read a morning paper today now knows, the current issue of JAMA contains two articles and an editorial based on documents released as part of the Vioxx lawsuits against Merck, showing evidence of ghostwriting and data manipulation. Little of this will be new to readers of HOOKED or this blog. Perhaps the most newsworthy point was the tone of JAMA's editorial, which might be describe as, "We're mad as hell and we're not going to take it any more." Or, as the editorial itself stated, "[Profound influence of the pharmaceutical and device industries over medical practice, education, and research] has occurred because physicians have allowed it to happen, and it is time to stop."
In news accounts Merck tried to minimize the damage by objecting that the authors of both papers had conflicts of interest because they had been employed by plaintiffs' attorneys in the lawsuits. (Funny how drug companies think that financial conflicts of interest are so damaging to one's credibility, as soon as the shoe is on the other foot.) JAMA makes no bones about these conflicts, acknowledging that only those involved with the lawsuits would normally have access to these documents in the first place. Just to assure that everything is kosher, JAMA took the unusual step of demanding that all of the original documents on which the authors relied be posted in publicly accessible websites that are referenced in the articles.
Ross et al. dealt with the issue of ghost and guest authorship, comparing correspondence between Merck and several medical communications companies regarding manuscripts being prepared for publication, with the actual publications in medical journals. (This is the same strategy Healy and Cattell employed in the best earlier paper on this topic, which made use of documents released by the Zoloft litigation.) When various drafts of the same article could be compared, they generally showed virtually no changes, thus negating any suggestion by the putative academic authors that they had carefully read and edited the manuscripts supplied for them by the ghostwriters. The practice most noted here, but not much discussed previously, is guest authorship, in which Merck in-house scientists wrote the paper but then added the names of academic scientists, often listing the academic as first or second author. Apparently, what has changed in recent years is that journal policies make it harder and harder completely to concal company sponsorship; indeed most of these articles disclose Merck funding. So the Merck scientists are listed openly as co-authors, only farther down the list, and the putative academic authors (who acually add little or nothing to the paper) are slipped in at the top.
Another tidbit in this paper is what the putative academic authors are paid for the use of their names. Ross et al. found fees of $750 to $2500 documented. In writing HOOKED, I could not find documented evidence of any fees of this sort greater than $1000, though when I mentioned that figure to several people closer than I am to the journal "biz," I received eye-rolls suggesting that I was on the low side. So it's nice to know what the going rate is for selling your integrity as a scientist.
Psaty and Kronmal recalculated the mortality rates from heart disease in two studies in which Merck tried to show that Vioxx would be good for preventing or reversing Alzheimer's--which flopped because it either did nothing or worsened the disease. They show that in both the published papers and in data submitted to the FDA, Merck managed to under-report the actual risk of heart disease deaths. Now that we know what we know, some of the data reported in the papers should have set off warning bells among journal editors and reviewers-- such as: "There were no drug-related deaths during the study. Non-drug related deaths occurred in 11 patients (9 in the rofecoxib group and 2 in the placebo group) while taking the study treatment or within 14 days of the last dose." Let's see--there were no "drug related" deaths, and purely by coincidence, more than four times as many patients who were taking Vioxx died compared to those taking placebo? Uh huh.
The editorial by DeAngelis and Fontanarosa lists a number of proposed reform measures, many of which are rather self-serving because they claim that if only all medical journals had the same stringent editorial policies as JAMA does, this sort of thing would not happen. The last in the list might easily be missed: "Individual physicians must be free of financial influences of pharmaceutical and medical devicde companies including serving on speaker's bureaus or accepting gifts." In other words, JAMA has belatedly come out in favor of the No Free Lunch pledge, AMSA's Pharm-Free campaign, and the National Physician's Alliance Unbranded Doctor campaign.
Ross JS, Hill KP, Egilman DS, Krumholz HM. Guest authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigation. JAMA 299:1800-12, April 16, 2008.
Psaty BM, Kronmal RA. Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment: a case study based on documents from rofecoxib litigation. JAMA 299:1813-17, April 16, 2008.
DeAngelis CD, Fontanarosa PB. Impugning the integrity of medical science: the adverse effect of industry influence. JAMA 299:1833-35, April 16, 2008.
Healy D, Cattell D. Interface betweem authorship, industry and science in the domain of therapeutics. Br J Psychiatry 183:22-27, 2003.