It's been a good while since I posted anything about exhorbitant gifts to docs or the incredible sums spent by drug firms on marketing, and you might have gotten the impression that things have changed. At least in Australia, apparently not.
The original source for this is
http://www.pharmainfocus.com.au/news.asp?newsid=2953, though you need a subscription to access, apparently. And this is a chance to say thanks to the Healthy Skepticism list serv for tipping me off to this news item.
Anyway, somebody apparently wondered what was the top Pharma event of the year so far Down Under, and the answer turns out to be--Wyeth's million-dollar weekend, dedicated to convincing docs to prescribe their new antidepressant, Pristiq (desvenlafaxine). The sum was reported to the oversight body, Medicines Australia, as tops on the list of all such events sponsored in that country between January and June 2009, with everything on the list sporting a total price tag of about $31M.
Now, you might wonder what it is about Pristiq that would make Wyeth want to spend $1M to promote it, and the answer seems pretty clear. Wyeth's old antidepressant is Effexor (venlafaxine). Effexor is going off patent and becoming available generically. If you remember your old organic chemistry class, you'll note that desvenlafaxine is probably the active stereoisomer of venlafaxine. In other words, all they did was tweak a tiny portion of the Effexor molecule and out came Pristiq--just as Prilosec became Nexium. The old evergreening trick once more, and a classic "me too" drug that has no advantage over older, and now cheaper drugs.
Sunday, September 27, 2009
UK Ahead of US in Disciplining Ghostwriting?
From Roy Poses' Health Care Renewal blog:
http://hcrenewal.blogspot.com/2009/09/reappearance-of-ghost-of-seasons-past.html
This post briefly reviews the case of Dr. Aubrey Blumsohn of Sheffield University, England, who was dismissed by his university some years ago after he went public with a dispute with a drug company (Procter & Gamble) sponsoring his bone research, demanding that he have the right to review all the relevant data. At the time his senior colleague at Sheffield, Dr. Richard Eastell, urged him to drop the matter and avoid offending such an important sponsor of University research.
Flash forward to today, and to reports in The Guardian that Dr. Eastell has been called before the UK's General Medical Council under charges of putting his name on ghostwritten papers. The specific allegation is--you guessed it--that he allowed his name to be put on papers for which he was unable to see all the relevant data.
Now, it would be nice to be able to report that justice was being done to Dr. Blumsohn, though it is a tad late for that. Still, I wanted to get a post up pronto on this topic because of a regular refrain in my previous posts on ghostwriting--when is a university ever going to take action against a star academic who's proven to have been involved in ghostwriting? OK, in this case it's the UK General Medical Council (sort of the equivalent of a state licensing board in the US) and not the University, but it does appear the Brits are out ahead of us in trying to do something about ghostwriting and the problem it poses for the integrity of the medical research literature.
http://hcrenewal.blogspot.com/2009/09/reappearance-of-ghost-of-seasons-past.html
This post briefly reviews the case of Dr. Aubrey Blumsohn of Sheffield University, England, who was dismissed by his university some years ago after he went public with a dispute with a drug company (Procter & Gamble) sponsoring his bone research, demanding that he have the right to review all the relevant data. At the time his senior colleague at Sheffield, Dr. Richard Eastell, urged him to drop the matter and avoid offending such an important sponsor of University research.
Flash forward to today, and to reports in The Guardian that Dr. Eastell has been called before the UK's General Medical Council under charges of putting his name on ghostwritten papers. The specific allegation is--you guessed it--that he allowed his name to be put on papers for which he was unable to see all the relevant data.
Now, it would be nice to be able to report that justice was being done to Dr. Blumsohn, though it is a tad late for that. Still, I wanted to get a post up pronto on this topic because of a regular refrain in my previous posts on ghostwriting--when is a university ever going to take action against a star academic who's proven to have been involved in ghostwriting? OK, in this case it's the UK General Medical Council (sort of the equivalent of a state licensing board in the US) and not the University, but it does appear the Brits are out ahead of us in trying to do something about ghostwriting and the problem it poses for the integrity of the medical research literature.
Wednesday, September 23, 2009
Unhealthy Skepticism about Flu Immunizations
Healthy Skepticism is a website that I have been proud to be a member of and that assisted me greatly in all of my research. I am a member of HS and also of a listserv that includes HS members and generally find it highly informative. So it pains me to have to dissociate myself from a recent thread on that listserv and website that I believe to be quite wrong. I am taking this public stance because I think the issue holds lessons for us Pharmascolds, in terms of how we can go too far in our opposition to the bad practices of the pharmaceutical industry.
My concern is with a piece posted on the HS site, "In the Face of Swine Flu, Common Sense and Science": http://www.healthyskepticism.org/news/2009/Oct09.php
The author is a Spanish GP who also holds a couple of academic posts. As a family physician I have been on the receiving end of attacks due to having dared to speak out on medical issues, when the relevant subspecialists thought that only they were entitled to express opinions. So I might have been expected to immediately identify with the author.
The basic thrust of the piece is that swine flu is an example of "disease mongering"; that the vaccine is unnecessary because the disease is very mild; the vaccine has been rushed into production and so cannot be known to be safe; and anyway, the seasonal flu vaccine has been overpromoted and is not really scientifically shown to be of benefit.
Let me separate my reactions into two parts--seasonal flu and swine flu.
I have followed the literature for many years on the health benefits of seasonal flu vaccines. (I personally always get my flu shot each fall, even though I am not now doing direct patient care.) I have been impressed with the nearly uniform showing in all studies that flu vaccines are highly beneficial and highly cost-effective. Indeed it is one of the most cost-effective preventive interventions available to us. So trying to cast doubt on the wisdom of a swine flu vaccine by attacking the benefits of the regular seasonal vaccine seems completely wrong-headed.
As to the swine flu, we charge the public health authorities with preparing a vaccine each year that will protect us from the dominant strain of flu that is going to appear in the fall. This year, the appearance of a novel strain of H1N1 flu (swine) created great concern because most Americans under age 60 have never been exposed to a similar flu virus, so natural immunity was thought to be very low. And indeed, at this time in the U.S., there are near-epidemic levels of flu, very unusual for this early in the fall, and more than 90 percent of it is H1N1 (though when they started making the vaccine, no one could have known this would necessarily happen). Every year the task of making the flu vaccine with the correct strains of antigen is a crap shoot and any year you could guess wrong. The swine flu is being manufactured using the same techniques as used for the seasonal flu, which has an excellent safety track record ever since 1976, the year of the last swine flu scare.
In short I see no reason whatever to interpret anything related to swine flu vaccination as a public health response, as somehow related to disease mongering by the pharmaceutical industry or its allies or shills.
Now, where the author of the HS piece questions the use of antivirals, I think he is on firmer ground. Antivirals for flu have in the past been significantly overpromoted.
The HS piece ends with this language:
"Note: The only purpose of the author is to transmit the best knowledge about the problem at present, and for that he has reviewed the world literature. This text is an informative one, not for clinical use. Sadly, the information you can obtain from others sources (public organizations, scientific societies, media) is very different; they will know why."
This appears to be a gratuitous ad hominem attack on anyone who disagrees with this author's conclusions, and seems utterly uncalled for.
I may add that I checked into a couple of the authors' citations, and was impressed that the conclusions reached by those articles did not square with the conclusions offered in the HS piece.
So why do I make a big deal of my personal disagreement with this particular piece of writing (one that HS was apparently proud enough of, to have translated into several languages for dissemination)? Again, I need to beware attributing motives to others. But we have to be very cautious that our distrust of the drug industry and its many devious and dishonest practices, and of our physician colleagues who eagerly do the industry's bidding, not spill over into areas where it does not belong. When we decide that any product manufactured by the drug industry is therefore unsafe or unneeded; or that any effort to raise public concern about a disease is therefore commercialized disease-mongering, then I think we have clearly crossed over that line.
My concern is with a piece posted on the HS site, "In the Face of Swine Flu, Common Sense and Science": http://www.healthyskepticism.org/news/2009/Oct09.php
The author is a Spanish GP who also holds a couple of academic posts. As a family physician I have been on the receiving end of attacks due to having dared to speak out on medical issues, when the relevant subspecialists thought that only they were entitled to express opinions. So I might have been expected to immediately identify with the author.
The basic thrust of the piece is that swine flu is an example of "disease mongering"; that the vaccine is unnecessary because the disease is very mild; the vaccine has been rushed into production and so cannot be known to be safe; and anyway, the seasonal flu vaccine has been overpromoted and is not really scientifically shown to be of benefit.
Let me separate my reactions into two parts--seasonal flu and swine flu.
I have followed the literature for many years on the health benefits of seasonal flu vaccines. (I personally always get my flu shot each fall, even though I am not now doing direct patient care.) I have been impressed with the nearly uniform showing in all studies that flu vaccines are highly beneficial and highly cost-effective. Indeed it is one of the most cost-effective preventive interventions available to us. So trying to cast doubt on the wisdom of a swine flu vaccine by attacking the benefits of the regular seasonal vaccine seems completely wrong-headed.
As to the swine flu, we charge the public health authorities with preparing a vaccine each year that will protect us from the dominant strain of flu that is going to appear in the fall. This year, the appearance of a novel strain of H1N1 flu (swine) created great concern because most Americans under age 60 have never been exposed to a similar flu virus, so natural immunity was thought to be very low. And indeed, at this time in the U.S., there are near-epidemic levels of flu, very unusual for this early in the fall, and more than 90 percent of it is H1N1 (though when they started making the vaccine, no one could have known this would necessarily happen). Every year the task of making the flu vaccine with the correct strains of antigen is a crap shoot and any year you could guess wrong. The swine flu is being manufactured using the same techniques as used for the seasonal flu, which has an excellent safety track record ever since 1976, the year of the last swine flu scare.
In short I see no reason whatever to interpret anything related to swine flu vaccination as a public health response, as somehow related to disease mongering by the pharmaceutical industry or its allies or shills.
Now, where the author of the HS piece questions the use of antivirals, I think he is on firmer ground. Antivirals for flu have in the past been significantly overpromoted.
The HS piece ends with this language:
"Note: The only purpose of the author is to transmit the best knowledge about the problem at present, and for that he has reviewed the world literature. This text is an informative one, not for clinical use. Sadly, the information you can obtain from others sources (public organizations, scientific societies, media) is very different; they will know why."
This appears to be a gratuitous ad hominem attack on anyone who disagrees with this author's conclusions, and seems utterly uncalled for.
I may add that I checked into a couple of the authors' citations, and was impressed that the conclusions reached by those articles did not square with the conclusions offered in the HS piece.
So why do I make a big deal of my personal disagreement with this particular piece of writing (one that HS was apparently proud enough of, to have translated into several languages for dissemination)? Again, I need to beware attributing motives to others. But we have to be very cautious that our distrust of the drug industry and its many devious and dishonest practices, and of our physician colleagues who eagerly do the industry's bidding, not spill over into areas where it does not belong. When we decide that any product manufactured by the drug industry is therefore unsafe or unneeded; or that any effort to raise public concern about a disease is therefore commercialized disease-mongering, then I think we have clearly crossed over that line.
Sunday, September 20, 2009
Nature on Grassley and Sunshine; How High Up the Food Chain?
A news article and an editorial in the British journal Nature offer a number of comment-worthy points. The editorial is open access:
http://www.nature.com/nature/journal/v461/n7262/full/461315a.html
The editorial speaks in praise of the Grassley-Kohl Physician Payment Sunshine Act and notes that it now stands a good chance of passing as part of any health reform bill that moves through Congress this year. (It was incorporated into the Baucus markup for the Senate Finance Committee last week.)
The news analysis by Meredith Wadman is primarily a profile of Paul Thacker, Grassley's principal staff investigator who's behind many of the most significant coups that the Iowa Republican has pulled off in the last few years, expopsing major academic physicians for serious underreporting of funding received from industry either to the NIH, to their home universities, or both.
The article spends a fair amount of time discussing the downfall of Emory University former Chair of Psychiatry, Charles Nemeroff, whose many escapades we have followed closely in this blog. Dr. Nemeroff apparently gave Wadman his first statement to the press after being disciplined by Emory: "I made mistakes in the area of conflict of interest for which I am sorry and remorseful. However, the mistakes I made were honest mistakes... in my view at the time, in keeping with my understanding of the current Emory policies.... I also plan to use my recent experience to help others avoid problems with conflict of interest from the lessons I have so painfully learned."
There are a couple of undercurrents in the Wadman article and also in the editorial that require some critical comment. Wadman quotes Joseph Cubells, a neurogeneticist at Emory, in defense of Nemeroff. Cubells objects that the case against Nemeroff is hardly as black and white as the media have made it out; and he also praises Nemeroff for "intellectual honesty," especially for including a psychotherapy-only comparison group in a major NIH study of depression that was temporarily halted because of the COI issues.
I concur with Cubells that comparing antidepressants to psychotherapy only is generally not a move designed to win friends among the drug industry, as long as the trial sets up a truly level playing field. However, his portrayal of Nemeroff as basically an honest guy who got tangled up in a complex set of morally confusing circumstances is not the impression that I get from some of my psychiatrist colleagues, who are quick to point to Nemeroff's national reputation within their field. The fact that he was commonly referred to by the nickname "boss of bosses" suggests that traits besides intellectual honesty were prominent in his character. If today he is truly repentent I give the man full credit.
The other important undercurrent in both the Wadman article and the editorial is the reminder that people like Nemeroff were (at least till recently) avidly recruited by academia because they promised to do just what their own bosses wanted--drive the gravy train of lucrative industry-funded research contracts straight through the university's front gate. If Emory treated their problem child with kid gloves for many years, it was clearly due to the ease with which he could have picked up his whole operation and moved to another university that would have been all too glad to welcome him and his Pharma bucks. As Wadman notes, at times, research grants from NIH and its daughter, the National Institute of Mental Health, specified that recipients should link up with industry to be sure that new discoveries were quickly brought to market to help patients faster.
That comment does, to my mind, offer something of a defense for at least a number of the academic docs now being pilloried for their COIs. The basic question is always the same--when there is bad behavior within an organization, how high up the food chain do you assign responsibility? Were the faculty who took all the industry cash the bad guys, or are they in effect taking the fall for their higher-up administrators who encouraged and abetted them?
Let's be blunt. Today, academic medical centers have got religion and are falling over each other to implement tough new COI policies. All of these COI policies are aimed at individual faculty. Supposedly if the faculty member brings in mucho Pharma research grants, he's golden. But if that same faculty member starts to line his own pockets with speaker's fees, consulting fees, and stock options, that spells trouble.
Now let's turn this around from the Big Pharma perspective. Two "key opinion leaders" from academic medical centers approach you for research funding. One of them says, "By the way, just so there's no confusion later on, I am very happy to perform legitimate scientific research for your firm. But I have strong views on individual COI and would prefer not to take any money for any other activities, such as your speakers' bureau and for consulting." The other doc is clearly ready to jump into bed with them for as high stakes as he can play.
With whom will the company rather do business with-- Goody Two Shoes? Or the doc who's made it clear that he's for sale? So who's most likely to land the really big research grant? And later on, who's more likely to be hobnobbing with the upper echelons of the drug firm, to be sure that he gets first dibs on the next big grant, and the next?
In short, by asking their top faculty to be squeaky clean on individual COI, but to be sure to keep the big Pharma money flowing onto campus, academic medical centers are sending their faculty a decidedly mixed message.
All of which is why, as I wrote in HOOKED, the really important COI policies are for institutional and not individual COI.
Wadman M. The senator's sleuth. Nature 461:330-34, 12 Sept. 2009.
http://www.nature.com/nature/journal/v461/n7262/full/461315a.html
The editorial speaks in praise of the Grassley-Kohl Physician Payment Sunshine Act and notes that it now stands a good chance of passing as part of any health reform bill that moves through Congress this year. (It was incorporated into the Baucus markup for the Senate Finance Committee last week.)
The news analysis by Meredith Wadman is primarily a profile of Paul Thacker, Grassley's principal staff investigator who's behind many of the most significant coups that the Iowa Republican has pulled off in the last few years, expopsing major academic physicians for serious underreporting of funding received from industry either to the NIH, to their home universities, or both.
The article spends a fair amount of time discussing the downfall of Emory University former Chair of Psychiatry, Charles Nemeroff, whose many escapades we have followed closely in this blog. Dr. Nemeroff apparently gave Wadman his first statement to the press after being disciplined by Emory: "I made mistakes in the area of conflict of interest for which I am sorry and remorseful. However, the mistakes I made were honest mistakes... in my view at the time, in keeping with my understanding of the current Emory policies.... I also plan to use my recent experience to help others avoid problems with conflict of interest from the lessons I have so painfully learned."
There are a couple of undercurrents in the Wadman article and also in the editorial that require some critical comment. Wadman quotes Joseph Cubells, a neurogeneticist at Emory, in defense of Nemeroff. Cubells objects that the case against Nemeroff is hardly as black and white as the media have made it out; and he also praises Nemeroff for "intellectual honesty," especially for including a psychotherapy-only comparison group in a major NIH study of depression that was temporarily halted because of the COI issues.
I concur with Cubells that comparing antidepressants to psychotherapy only is generally not a move designed to win friends among the drug industry, as long as the trial sets up a truly level playing field. However, his portrayal of Nemeroff as basically an honest guy who got tangled up in a complex set of morally confusing circumstances is not the impression that I get from some of my psychiatrist colleagues, who are quick to point to Nemeroff's national reputation within their field. The fact that he was commonly referred to by the nickname "boss of bosses" suggests that traits besides intellectual honesty were prominent in his character. If today he is truly repentent I give the man full credit.
The other important undercurrent in both the Wadman article and the editorial is the reminder that people like Nemeroff were (at least till recently) avidly recruited by academia because they promised to do just what their own bosses wanted--drive the gravy train of lucrative industry-funded research contracts straight through the university's front gate. If Emory treated their problem child with kid gloves for many years, it was clearly due to the ease with which he could have picked up his whole operation and moved to another university that would have been all too glad to welcome him and his Pharma bucks. As Wadman notes, at times, research grants from NIH and its daughter, the National Institute of Mental Health, specified that recipients should link up with industry to be sure that new discoveries were quickly brought to market to help patients faster.
That comment does, to my mind, offer something of a defense for at least a number of the academic docs now being pilloried for their COIs. The basic question is always the same--when there is bad behavior within an organization, how high up the food chain do you assign responsibility? Were the faculty who took all the industry cash the bad guys, or are they in effect taking the fall for their higher-up administrators who encouraged and abetted them?
Let's be blunt. Today, academic medical centers have got religion and are falling over each other to implement tough new COI policies. All of these COI policies are aimed at individual faculty. Supposedly if the faculty member brings in mucho Pharma research grants, he's golden. But if that same faculty member starts to line his own pockets with speaker's fees, consulting fees, and stock options, that spells trouble.
Now let's turn this around from the Big Pharma perspective. Two "key opinion leaders" from academic medical centers approach you for research funding. One of them says, "By the way, just so there's no confusion later on, I am very happy to perform legitimate scientific research for your firm. But I have strong views on individual COI and would prefer not to take any money for any other activities, such as your speakers' bureau and for consulting." The other doc is clearly ready to jump into bed with them for as high stakes as he can play.
With whom will the company rather do business with-- Goody Two Shoes? Or the doc who's made it clear that he's for sale? So who's most likely to land the really big research grant? And later on, who's more likely to be hobnobbing with the upper echelons of the drug firm, to be sure that he gets first dibs on the next big grant, and the next?
In short, by asking their top faculty to be squeaky clean on individual COI, but to be sure to keep the big Pharma money flowing onto campus, academic medical centers are sending their faculty a decidedly mixed message.
All of which is why, as I wrote in HOOKED, the really important COI policies are for institutional and not individual COI.
Wadman M. The senator's sleuth. Nature 461:330-34, 12 Sept. 2009.
Friday, September 18, 2009
Enter the Ghostbusters
While I have been out to lunch recently (actually, out of town for part of the time) and not blogging, the Pharma/medicine news has kept rolling in. Fortunately my fellow bloggers have been on the job. One big story is a paper written by some of the editorial staff of JAMA, as yet not peer reviewed or published in a journal, but presented at a conference, and covered by the New York Times:
http://www.nytimes.com/2009/09/11/business/11ghost.html?_r=2&ref=health
http://www.nytimes.com/2009/09/18/business/18ghost.html?adxnnl=1&adxnnlx=1253297183-lE6NkNPm04y/UvAkfSXwJg
The study, by Joseph Wislar and colleagues, asked authors listed for 630 articles in 6 top medical journals to respond to an anonymous on line questionnaire. The results suggested that 7.8 percent of these articles had been ghostwritten. The New England Journal actually topped out the other journals at 10.9 percent, leading its editors to throw the most skeptical barbs at their rival journal's study. However, most believe that the problem in any study such as this is underreporting rather than over-, hence suggesting that the true rate is probably even higher.
In response to my earlier question about whether journal editors are taking this seriously enough and doing all they can to police themselves, the second Times article highlighted a nice editorial in Blood. (That's not a Halloween publication but rather the official journal of the American Society of Hematology.) There, editors Cynthia E. Dunbar and Martin S. Tallman reported back in January that one reviewer became suspicious of an unsolicited review manuscript submitted by "a prominent clinical investigator." The academic acknowledged the assistance of another peron, without specifying what role that other person played. The reviewer happened to know that the other person worked for a pharmaceutical company, whose product was prominently featured in the review article. (The pharmaceutical connection was also not disclosed.) Following more investigation, the editors decided this was actually a ghostwritten article and rejected it. The editors added, "Once we began to systematically seek clarification of the degree to which a pharmaceutical company had been involved in any aspect of writing, editing, or researching review articles, within 2 weeks we had rejected 2 additional unsolicited manuscripts. "
This bit of anecdotal testimony perhaps helps answer the question--just how common is ghostwriting--and tends to confirm previous reports that it is all too common. The poohbahs for the drug industry interviewed by the Times naturally insisted that the industry was doing all it could to implement new guidelines (expected in October) to bring industry practices in line with the international medical journal editors' proposed rules. To which the obvious reply is--why so late? Given that these rules were promulgated years ago, and the ghostwriting issue has also received publicity for many years, why is the industry only now taking action? For that they expect a pat on the back? (The industry also objected strenuously to proposals that any academic author caught signing a ghostwritten article be banned from further publishing in that journal for some period--it would "chill" research, they feared.)
The Blood editors also very kindly summarized for us an incident I wrote about in HOOKED which reminds us as to why all this is important:
"If our appeal to better instincts is insufficient, read the New York Times account of the Annals of Internal Medicine paper on a Vioxx clinical trial that failed to include the deaths of several patients. The paper's first author admitted that "Merck designed the trial, paid for the trial, ran the trial ... Merck came to me after the study was completed and said, ‘We want your help to work on the paper.’ The initial paper was written at Merck and then it was sent to me for editing." Documents made public in court indicated that Merck's marketing department initiated and managed this trial solely as a mechanism for exposing a wide swath of primary care physicians to the drug, instead of pursuing real research questions." [citations omitted]
Dunbar CE, Tallman MS. "Ghostbusting" at Blood. Blood 113:502-3, 2009.
http://www.nytimes.com/2009/09/11/business/11ghost.html?_r=2&ref=health
http://www.nytimes.com/2009/09/18/business/18ghost.html?adxnnl=1&adxnnlx=1253297183-lE6NkNPm04y/UvAkfSXwJg
The study, by Joseph Wislar and colleagues, asked authors listed for 630 articles in 6 top medical journals to respond to an anonymous on line questionnaire. The results suggested that 7.8 percent of these articles had been ghostwritten. The New England Journal actually topped out the other journals at 10.9 percent, leading its editors to throw the most skeptical barbs at their rival journal's study. However, most believe that the problem in any study such as this is underreporting rather than over-, hence suggesting that the true rate is probably even higher.
In response to my earlier question about whether journal editors are taking this seriously enough and doing all they can to police themselves, the second Times article highlighted a nice editorial in Blood. (That's not a Halloween publication but rather the official journal of the American Society of Hematology.) There, editors Cynthia E. Dunbar and Martin S. Tallman reported back in January that one reviewer became suspicious of an unsolicited review manuscript submitted by "a prominent clinical investigator." The academic acknowledged the assistance of another peron, without specifying what role that other person played. The reviewer happened to know that the other person worked for a pharmaceutical company, whose product was prominently featured in the review article. (The pharmaceutical connection was also not disclosed.) Following more investigation, the editors decided this was actually a ghostwritten article and rejected it. The editors added, "Once we began to systematically seek clarification of the degree to which a pharmaceutical company had been involved in any aspect of writing, editing, or researching review articles, within 2 weeks we had rejected 2 additional unsolicited manuscripts. "
This bit of anecdotal testimony perhaps helps answer the question--just how common is ghostwriting--and tends to confirm previous reports that it is all too common. The poohbahs for the drug industry interviewed by the Times naturally insisted that the industry was doing all it could to implement new guidelines (expected in October) to bring industry practices in line with the international medical journal editors' proposed rules. To which the obvious reply is--why so late? Given that these rules were promulgated years ago, and the ghostwriting issue has also received publicity for many years, why is the industry only now taking action? For that they expect a pat on the back? (The industry also objected strenuously to proposals that any academic author caught signing a ghostwritten article be banned from further publishing in that journal for some period--it would "chill" research, they feared.)
The Blood editors also very kindly summarized for us an incident I wrote about in HOOKED which reminds us as to why all this is important:
"If our appeal to better instincts is insufficient, read the New York Times account of the Annals of Internal Medicine paper on a Vioxx clinical trial that failed to include the deaths of several patients. The paper's first author admitted that "Merck designed the trial, paid for the trial, ran the trial ... Merck came to me after the study was completed and said, ‘We want your help to work on the paper.’ The initial paper was written at Merck and then it was sent to me for editing." Documents made public in court indicated that Merck's marketing department initiated and managed this trial solely as a mechanism for exposing a wide swath of primary care physicians to the drug, instead of pursuing real research questions." [citations omitted]
Dunbar CE, Tallman MS. "Ghostbusting" at Blood. Blood 113:502-3, 2009.
Wednesday, September 9, 2009
Who's Insulting Whom?
Our friend Danny Carlat has devoted his recent blog posting:
http://carlatpsychiatry.blogspot.com/2009/09/schering-plough-to-saphris-drug-whores.html
...to the mailing he received from Schering-Plough regarding their new psychiatric medication. Seems they did not quite get it when Dr. Carlat famously came out of the closet in the national media spotlight as a former paid drug company speaker who had seen the light and vowed to sin no more. They offered him lucrative deals if he'd agree to join the speakers' bureau for the new drug, with a chance to earn up to $170,000 annually. (If you want to see the hourly rates check the blog posting.)
As you can see by the URL above, Dr. Carlat initially had the bad manners to refer to his colleagues who did sign up for the speakers' bureau as "drug whores." That led to a couple of interesting comments on his blog. One commentator objected to the derogatory word "whores" as a form of discrimination against female sex workers who, virtually universally, would be very happy not to be paid sex workers, if only they had a realistic option. Dr. Carlat agreed and so his post is now titled, "Schering-Plough to SAPHRIS Hired Guns: Come and Get It!"
That put me in mind of one of my favorite newspaper letters to the editor. Many years ago, during the infamous OJ trial, a common remark made in the media was that the antics of the defense attorneys were "turning the courtroom into a circus." That led to a letter from a circus ringmaster, who explained in some detail exactly how carefully planned and structured were all the events that went on in all three rings of his circus at any given time. He expressed his sense of insult that anyone would compare his very neatly orchestrated circus with the godawful mess that was the courtroom in question.
So now we have it, my fellow physicians. Female sex workers don't have any real choice as to how to earn a buck. We physicians do. So we ought not call the physicians who become paid speakers for the drug industry "whores," lest we insult the sex workers by the comparison.
http://carlatpsychiatry.blogspot.com/2009/09/schering-plough-to-saphris-drug-whores.html
...to the mailing he received from Schering-Plough regarding their new psychiatric medication. Seems they did not quite get it when Dr. Carlat famously came out of the closet in the national media spotlight as a former paid drug company speaker who had seen the light and vowed to sin no more. They offered him lucrative deals if he'd agree to join the speakers' bureau for the new drug, with a chance to earn up to $170,000 annually. (If you want to see the hourly rates check the blog posting.)
As you can see by the URL above, Dr. Carlat initially had the bad manners to refer to his colleagues who did sign up for the speakers' bureau as "drug whores." That led to a couple of interesting comments on his blog. One commentator objected to the derogatory word "whores" as a form of discrimination against female sex workers who, virtually universally, would be very happy not to be paid sex workers, if only they had a realistic option. Dr. Carlat agreed and so his post is now titled, "Schering-Plough to SAPHRIS Hired Guns: Come and Get It!"
That put me in mind of one of my favorite newspaper letters to the editor. Many years ago, during the infamous OJ trial, a common remark made in the media was that the antics of the defense attorneys were "turning the courtroom into a circus." That led to a letter from a circus ringmaster, who explained in some detail exactly how carefully planned and structured were all the events that went on in all three rings of his circus at any given time. He expressed his sense of insult that anyone would compare his very neatly orchestrated circus with the godawful mess that was the courtroom in question.
So now we have it, my fellow physicians. Female sex workers don't have any real choice as to how to earn a buck. We physicians do. So we ought not call the physicians who become paid speakers for the drug industry "whores," lest we insult the sex workers by the comparison.
Sunday, September 6, 2009
Registering Clinical Trials--Less than Meets the Eye?
The current JAMA features an article (subscription needed to access) by an international team of authors headed by Dr. Sylvain Mathieu of Paris. The authors decided to study what has happened as a result of the requirements from leading medical journals (initiated in 2005) that all clinical trials should be properly registered--in theory allowing anyone to compare the final, published results of the trial with the original design.
They found 323 trials that were published in 2008 in high-impact medical journals, either general or in one of 3 specialties (cardiology, rheumatology, gastroenterology). They discovered that only 45% of these were adequately registered. Others were not registered until the trial had been completed (14%), and with no or an unclear description of the primary outcome (12%). More than a quarter were not registered at all.
In about half the cases, there were insufficient data to determine what sort of bias would have been introduced by a change in the primary outcome from that originally identified in the study methods to the one featured in the published report. In the other half, in 19 of 23 studies, an outcome for which the results were statistically insignificant was replaced by an outcome whose results were significant.
Naturally a person like me would wonder--and what association did commercial sponsorship have with whether the authors ended up playing fast and loose with the study design? About 56% of the trials in this review were commercially sponsored (and sponsorship was not reported in another 9%). That would seemingly have allowed some comparisons to be made. But these authors reported no data based on associations with commercial sponsorship.
The most worrisome finding was that the authors found evidence of selective outcome reporting in 28% of studies that were properly registered. This suggests that neither the editors nor the reviewers took the time and trouble to use data available in open trial registries to see whether the outcomes reported in the final publication were indeed the outcomes listed in the pre-trial study design. In short, in these instances, the whole reason for trial registration was subverted by the failure of journals to take advantage of the data.
So let's leave aside the question that we wish had been answered, but was not--whether commercially sponsored studies were more likely to be registered incorrectly or incompletely, or to have partial or biased reporting of endpoints. We have long asked--why do articles get published in major medical journals that are ghostwritten or that suppress key data in the interests of marketing drugs? The usual reply from the journal editors is that they are not detectives. If the authors flat-out lie to them about who wrote the article, or what the endpoints were, how is the journal going to smell a rat? In a previous post (http://brodyhooked.blogspot.com/2009/08/read-em-and-weep-wyeth-ghostwriting.html) I noted the criticism that even if journal editors lack the detective facilities to identify ghostwritten articles, that hardly explains why no article has as yet been officially retracted by a journal once ghostwriting was proven by another route. Now, in light of the Mathieu study, journal editors need to explain why they cannot be bothered to cross-check trial reports against registered data that are available in plain sight.
It appears that it's not simply the case that journal editors make rotten detectives. Journal editors don't seem to run a very tight ship even when other people do the detective work for them and hand them the results neatly giftwrapped.
Clinical trial registries were supposed to solve this problem. Do we have here yet another example of Epstein's Law--"If you think the problem is bad now, just wait till you've solved it"?
Mathieu S, Boutron I, Moher D, Altman DG, Ravaud P. Comparison of registered and published primary outcomes in randomized controlled trials. JAMA 302:977-84, Sept. 2, 2009.
They found 323 trials that were published in 2008 in high-impact medical journals, either general or in one of 3 specialties (cardiology, rheumatology, gastroenterology). They discovered that only 45% of these were adequately registered. Others were not registered until the trial had been completed (14%), and with no or an unclear description of the primary outcome (12%). More than a quarter were not registered at all.
In about half the cases, there were insufficient data to determine what sort of bias would have been introduced by a change in the primary outcome from that originally identified in the study methods to the one featured in the published report. In the other half, in 19 of 23 studies, an outcome for which the results were statistically insignificant was replaced by an outcome whose results were significant.
Naturally a person like me would wonder--and what association did commercial sponsorship have with whether the authors ended up playing fast and loose with the study design? About 56% of the trials in this review were commercially sponsored (and sponsorship was not reported in another 9%). That would seemingly have allowed some comparisons to be made. But these authors reported no data based on associations with commercial sponsorship.
The most worrisome finding was that the authors found evidence of selective outcome reporting in 28% of studies that were properly registered. This suggests that neither the editors nor the reviewers took the time and trouble to use data available in open trial registries to see whether the outcomes reported in the final publication were indeed the outcomes listed in the pre-trial study design. In short, in these instances, the whole reason for trial registration was subverted by the failure of journals to take advantage of the data.
So let's leave aside the question that we wish had been answered, but was not--whether commercially sponsored studies were more likely to be registered incorrectly or incompletely, or to have partial or biased reporting of endpoints. We have long asked--why do articles get published in major medical journals that are ghostwritten or that suppress key data in the interests of marketing drugs? The usual reply from the journal editors is that they are not detectives. If the authors flat-out lie to them about who wrote the article, or what the endpoints were, how is the journal going to smell a rat? In a previous post (http://brodyhooked.blogspot.com/2009/08/read-em-and-weep-wyeth-ghostwriting.html) I noted the criticism that even if journal editors lack the detective facilities to identify ghostwritten articles, that hardly explains why no article has as yet been officially retracted by a journal once ghostwriting was proven by another route. Now, in light of the Mathieu study, journal editors need to explain why they cannot be bothered to cross-check trial reports against registered data that are available in plain sight.
It appears that it's not simply the case that journal editors make rotten detectives. Journal editors don't seem to run a very tight ship even when other people do the detective work for them and hand them the results neatly giftwrapped.
Clinical trial registries were supposed to solve this problem. Do we have here yet another example of Epstein's Law--"If you think the problem is bad now, just wait till you've solved it"?
Mathieu S, Boutron I, Moher D, Altman DG, Ravaud P. Comparison of registered and published primary outcomes in randomized controlled trials. JAMA 302:977-84, Sept. 2, 2009.
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