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Threats to science-based medicine: Pharma ghostwriting (revisited)

Here and elsewhere in the blogosphere, over the last several years, what started out as a more general interest in skepticism and science with a natural focus on medicine and a side interest in combatting Holocaust denial became more focused on promoting science-based medicine. As the saying goes, “Science, it works, bitches,” and I make no apologies for promoting science-based medicine as the best medicine and applying skepticism and science to claims of purveyors of unscientific so-called “alternative” medicine advocates and anti-vaccine loons. However, I am not blind to the shortcomings of SBM, the claims otherwise of those who really, really don’t like me notwithstanding. I’ve even written about them right here on this very blog (and elsewhere). However, I continue to steal ruthlessly from Winston Churchill when he said, “Many forms of Government have been tried and will be tried in this world of sin and woe. No one pretends that democracy is perfect or all-wise. Indeed, it has been said that democracy is the worst form of government except all those other forms that have been tried from time to time.”

The same thing goes for SBM. It’s the worst form of medicine–except for all those other forms that have been tried before. (Look for some enterprising woo-meister to quote mine that passage.)

One of the most important aspects of SBM–actually all of science–is the peer-reviewed scientific literature. There, scientists report their findings, after they have been subjected to peer review, for other scientists to examine, replicate and expand on, and, quite often, attack ruthlessly. It is through a ruthless, Darwinian selection process that poor science is either overturned or forgotten and good science is confirmed and expanded upon to use as a basis to improve upon. This process is incredibly messy, particularly in medicine and particularly to lay people who are not used to the rather nasty testing to which scientists naturally subject each other’s work to, which is perhaps one reason why alt-med advocates often have a hard time handling scientific criticism that is actually not even particularly harsh. Be that as it may, SBM can be quite frustrating in that it may take much longer than one would expect to change in response to new evidence, but if there’s one thing that distinguishes SBM from woo is that it actually does change in response to evidence, casting aside therapies that do not work or do not work as well in favor of therapies that work better. The peer-reviewed scientific literature is how that new scientific information is distributed to physicians. If the peer-reviewed scientific literature is corrupted, then the information that physicians receive is corrupted.

Yesterday, I was depressed to see Steve Novella take on a Policy Forum article in PLoS Medicine by Adriane J. Fugh-Berma of the Department of Physiology and Biophysics at Georgetown University entitled The Haunting of Medical Journals: How Ghostwriting Sold “HRT”. Steve did his usual fantastic job of looking at the article and the practice of pharma ghostwriting, but I decided that I needed to comment on the article as well, mainly because of how related to my area of specialty it is. Hormone replacement therapy (HRT) is a textbook example of how medicine can at times embrace a therapy before its’ ready for prime time to the point that the therapy can even become the standard of care. It’s also a topic I have discussed before in the context of HRT. Basically, the first time around I expressed my outrage at a particularly egregious example of allowing pharma ghostwriting on the topic of HRT. In particular, I could not understand how Dr. Gloria Bachman, professor of obstetrics and gynecology at the Robert Wood Johnson Medical School in New Brunswick, NJ, in essence allowed a minion of Wyeth Pharmaceuticals working through a company contracted by the pharmaceutical company to write a 14 page review article that Bachman published almost unchanged in The Journal of Reproductive Medicine in 2005.

In his PLoS Medicine article, Fugh-Berman tells the tale of how a company hired by Wyeth called DesignWrite did far more than just publish one ghostwritten review article upon which it pasted just one academic physician’s name.In reality, Dr. Bachman’s betrayal of her academic position was but a small part of DesignWrite’s scheme. The scheme, which was designed as a way of getting around FDA regulations on advertising claims for pharmaceuticals:

It is illegal for pharmaceutical companies to promote a marketed drug for off-label use, i.e., for uses other than those approved by the U.S. Food and Drug Administration (FDA) or equivalent national agencies. Articles in medical journals, newsletters, and magazines, however, are not considered promotional. As an industry article states, “Peer-reviewed publications offer pharma companies shelter from often-stormy regulatory waters. FDA views published articles as protected commercial speech so doesn’t regulate their content” [29].

In the absence of data (or in the presence of data adverse to marketing goals), review articles in medical journals are crucial vehicles for encouraging off-label uses, promoting unproven benefits, and for downplaying harms. Narrative reviews summarize and analyze prevailing literature and often offer clinical recommendations [30]. Commentaries and other opinion pieces are also highly valued because they provide clinical direction, and are usually not peer-reviewed. Presentations at medical meetings are important for the same reason [30].

Of course, besides the First Amendment, one reason why speech in peer-reviewed journals is generally considered not to be on the same level of advertising is because it is peer-reviewed. The peer review is supposed to make sure that the factual information in articles is, well, factual. However, one thing peer review can’t necessarily do–or at least can’t do as well– is to comment on the conclusions authors of review articles draw from the evidence they present. After all, by their very nature, most review articles are in essence commentary. Most reviewers will therefore concentrate on the facts and only intervene if the conclusions being drawn from those facts are egregiously out of line with the facts presented or if well-known contradictory information and data are not acknowledged and discussed. Commentaries can get away with even more because they are often not peer reviewed. On the surface, none of this is necessarily wrong or deceptive. Rather, it’s just how scientists and physicians publicly debate the data and the clinical recommendations that flow from that data.

There are, however, three assumptions behind these reviews, editorials, and commentaries, and those assumption are (1) that the authors of these articles are honest brokers; (2) that the authors actually wrote the review articles; and (3) that what the authors write represents their opinion. Indeed, that is the same assumption that goes into the peer review of these articles as well. In other words, no matter how extreme or strongly argued the opinion, there is the assumption that it is an honest opinion presented by the academics holding it. Moreover, it is quite common for academics to argue for the off-label use of various drugs, and there is nothing wrong with that. Off-label use is not necessarily non-science-based, nor is it illegal or even against the standard of care.. Sometimes off-label use can be quite science-based in that it is simply ahead of its time, with some clinical trials having been done but not enough (yet) for an application to the FDA. However, the FDA quite correctly does not allow pharmaceutical companies to advertise their drugs for off-label indications for the simple reason that, if such advertising were allowed, then drug companies would have no incentive to do the clinical trials to get their drugs approved for additional indications. All they’d have to do is to get approval for one indication and then advertise for any other indication they want. In contrast, physicians are perfectly free to advocate for off-label uses.

To take advantage of this DesignWrite designed a comprehensive plan, which Fugh-Berman describes:

As Table 1 shows, DesignWrite helped to produce numerous ghostwritten reviews and commentaries, including articles designed to promote the off-label use of Prempro for preventing Alzheimer’s disease, Parkinson’s disease, age-related macular degeneration, and wrinkles. The scope of these articles is summarized in Box 1. The DesignWrite documents avoid discussing off-label marketing, but noted that reviews can “Disseminate messages that fill the gaps not addressed by current studies” [31]. Another document noted that the “Strategic Publications Team” should “Identify data gaps” and “Fill the gap with review papers” [32].

This even went so far as DesignWrite “managing” a stable of authors:

An important part of DesignWrite’s work for Wyeth was to manage “authors” and journals. There is evidence in unsealed DesignWrite documents that although some authors signed off on ghostwritten articles, others insisted on contributing to their articles. One co-author seemed puzzled by the concept that she was to author, but not write, an article [34]: “From what you have written, I would be more of an ‘editor’ rather than the major writer–that is, you guys would be writing the versions–with me ‘altering, editing, etc.? Is that correct?'” This query was in response to an e-mail from Karen Mittleman (a DesignWrite employee who supervised medical writers) that stated: “The beauty of this process is that we become your postdocs! … We provide you with an outline that you review and suggest changes to. We then develop a draft from the final outline. You have complete editorial control of the paper, but we provide you with the materials to review/critique” [34].

So what’s wrong with this? A lot. The biggest problem with this is that there are an uncredited co-authors (the ghostwriters from DesignWrite) who are employed by the pharmaceutical company making the drug that is the topic of the review article. In the case of HRT, these articles were designed to be marketing materials, not objective (or even not-so-objective) commentaries or review articles. The “authors” (who don’t deserve the appellation, given that they in essence just put their names on articles to which they contributed relatively little) could suggest changes, and DesignWrite would even incorporate them–as long as the changes didn’t compromise the marketing message.

There were many marketing messages, too. In the case of HRT, the marketing messages were many. They included promoting the cardiovascular benefits of HRT (which, as later studies showed), were vastly overblown and in fact nonexistent; sliming the competition (generics); and, most relevant to my specialty, trying to downplay the connection between HRT and increased risk of breast cancer, complete with a number of “talking points”:

  • Cast doubt on the link between HT and breast cancer
  • Questioned whether HT-induced changes in mammographic density were related to increased breast cancer risk
  • Implied that use of estrogen after breast cancer was safe
  • Promoted the concept that HT-associated breast cancers were less aggressive cancers

Regarding point number one, the Women’s Health Initiative (WHI) study, whose results were published in 2002, was the final nail in the coffin of claims by promoters of HRT for cardiovascular benefits. Even more alarming, the WHI found an increased risk of breast cancer. Indeed, since the WHI study was published and HRT use plummeted, the incidence of breast cancer has decreased. As for the other points, mammographic density is related to breast cancer risk; that is becoming more and more clear, not to mention an increasing area of research interest among investigators whom I know. In any case, the DesignWrite campaign, undertaken on behalf of Wyeth, has all the classic earmarks of a denialist campaign every bit as deceptive as that undertaken by tobacco companies.

And, as was the case with tobacco, academic physicians were complicit in the campaign.

I have to agree with Fugh-Berman when she asserts that “medicine, as a profession, must take responsibility for this situation,” and that “naïveté is no longer an excuse.” It’s true. Five or ten years ago it may have been possible for an academic physician to plead naïveté, but no more after this incident and other prominent examples of pharma ghostwriting. I do feel obligated to point out, though, that Fugh-Berman does have an agenda. She is an Associate Professor of Complementary and Alternative Medicine at Georgetown University, which earned my wrath years ago for requiring the teaching of non-science-based quackery “alternative medicine.” That she is correct to castigate the practice of pharma ghostwriting now does not mean I don’t keep in mind that she clearly has a bug up her behind about pharma that appears to be at least in part based on her belief in the glories of CAM. (I know through the grapevine that Fugh-Berman has a rather credulous attitude towards, for example, homeopathy.)

Be that as it may, like Steve Novella, I have never personally encountered an example of ghostwriting, but, also like Steve, I don’t think that necessarily means anything. For one thing, as much as I’d like to pretend otherwise, I am not a “thought leader” highly sought out by ghostwriters to spread their message, and the true thought leaders that I’ve worked with during my career are so well-published as to be virtually immune to the need for just one more publication. I don’t have any data to confirm this, but it appears to me that DesignWrite tended to target early mid-career academics who had made a name for themselves may have been up for promotion or tenure and could use every paper they could get. Those are the most vulnerable of academics, and, having recently been in a position where I really, really needed some papers, I can fully understand how it would be very tempting if a pharma minion from DesignWrite came up to me with a prewritten article that I could publish under my own name. However, I would resist, and we as academics have the duty to resist.

SBM works best in the light of day, where there is full disclosure, and I don’t view pharmaceutical companies as inherently evil, as some do. They are, however, profit-making companies with every right to market their legal products, but competing against that is medical profession’s need to know what is science, what is opinion, and what is advertising. The reason ghostwriting is so disturbing to me is not so much that a pharmaceutical company helped academics write their review articles but rather that not all the coauthors’ identities and affiliations were revealed. I rather suspect that, if they knew that multiple authors of an article were employees of a commercial company hired by a pharmaceutical company, editors would be less likely to publish the article and physicians would be less likely to read it or take its recommendations to heart. That’s why the light of day needs ot be shone on the entire process, so that the cockroaches will go scuttling back under their rocks. SBM demands it.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

33 replies on “Threats to science-based medicine: Pharma ghostwriting (revisited)”

I don’t see any way that the authors of record for ghostwritten articles have not committed scientific misconduct.

Using someone else’s work without attribution is plagiarism and fraud. It doesn’t matter if they say it is ok to do so. It is still scientific misconduct.

Those ghostwritten articles should be retracted, or at the very least corrected to show who the true authors are and what their conflicts of interest are.

The journals in question should sue the author of record and the ghostwriters and their employer for fraud, to recover the costs of the fraud on the journal and the cost of mitigating the fraud by publishing retractions and the details of how it happened (including the labor of the investigation). Maybe there isn’t a way to “reach though” the author of record to hit the ghostwriters and the pharmaceutical company behind them legally, in which case the author of record is liable for the whole cost. If you were able to invoke RICO as a conspiracy, then the pharmaceutical company could be hit for triple damages.

I don’t see any way that the authors of record for ghostwritten articles have not committed scientific misconduct.

As have the unattributed (real) authors of the paper. They are using deception to give the impression that someone besides them wrote the paper.

As I mentioned on Dr. Novella’s article about ghostwriting over at Science-Based Medicine, the law should be changed to allow FDA the ability to go after off-label marketing like this. They can already take action against companies, IIRC, for marketing at medical conferences under the guise of “educational seminars”.

If a company engages in ghostwriting journal articles in this manner, it is marketing, plain and simple. As such, it is in violation of FDA regulations and the company should face the same punishments as if they had placed an overt ad for the off-label use (or if for on-label, if it were in any way false or misleading, per the regulations), ranging from warning letters and fines to revocation of approval for the product.

Of course, thanks to Master Crosby, we all know that Orac would not have written this article if it had been Sanofi-Aventis that was found to have engaged in ghostwriting. Right?

Seconding (thirding?) what daedalus2u and Pablo said — it is scientific misconduct to do this, in my opinion, and it sullies the reputation of every researcher who lets their name be used in this way. It is nothing more than concealing a massive conflict of interest on the parts of the true authors — and intentionally, because the true authors do not consider that conflict of interest to be a problem, because they are quite clear as to where their loyalties lie.

The scientists who signed on to this should be ashamed. The journals who published this material should be ashamed as well, and I could see blacklisting the affected authors or at least being extremely wary of any new material submitted by them.

Callie, I agree with you that the authors and the researchers should be ashamed, but why the journals? They almost certainly believed that the named authors were the real authors and acted in good faith. I don’t see what the journals did to be ashamed of.

In professional rather than creative writing the signature means, “I stand by all the above.” This can be true even if someone else writes the first draft or polishes the final draft.

I personally don’t have a problem with uncredited, consensual co-authorship. Secretaries, junior staff, employees, friends, spouses, and professional writers all contribute substantially to various reports and speeches without being named.

However, the stealth marketing aspect of the Wyeth story is troubling, as it suggests a coordinated effort to create the *appearance* of independent opinion from divergent sources.

Every word in the ghostwritten articles might be true. The lie would be in having several voices echoing a particular truth when some might more naturally have their attention elsewhere.

Three connected people saying the same thing are not the same as three independent people saying the same thing.

I agree with Orac’s point about transparency being the solution to the problem. Transparency should alert us to covert marketing campaigns –what we NO WANTS in science. I merely disagree with the condemnation of ghostwriting in general as somehow unethical.

titmouse – but in scientific writing, every contributor is named and their contributions and COI’s made transparent. This serves to ensure that people get proper credit for their work, and that the process is transparent.

It is simply not acceptable to have ghostwriters on scientific papers.

Interesting note there about Fugh-Berman’s agenda and affiliations. Of course, it’s not at all unprecedented that advocates for a wrong-headed cause or who take the cause too far wind up uncovering legitimate wrong-doing. I’m thinking analogously here of some of the illegal treatment of animals that PETA has uncovered at some factory farms. I do not buy most of PETA’s agenda, but that does not minimize the seriousness of the wrongdoing they have at times highlighted.

However, Orac, as a licensed pharma shill, you clearly should be criticizing whatever Fugh-Bergman has to say, regardless of whether she is right or not. They’re liable to cut off your secret payments!

Pablo, it’s because the journals don’t seem to be pissed that I think they should be ashamed. They are in the best position, IMHO, to stop this sort of thing, by making it professional suicide to associate with a ghostwriter. I haven’t heard of these papers being withdrawn or anything like that; it’s as if the journals either don’t mind the practice or just refuse to take the problem seriously. Mind you, I’m an engineer; I don’t read enough journals to know if these papers get routinely withdrawn or if it ever does come back to haunt these straw authors.

Though I have only one academic paper to my name, I’ll echo Steve Novella’s reply to titmouse, and add my two cents on one clarifying point: I think it’s more or less okay on academic papers for a named author to have contributed very little to the actual paper itself, though they really ought to have made some kind of serious contribution to some stage of the paper (e.g. supervising the research, advising the project, etc.) Even then, slapping some extra authors’ names on a paper who really probably shouldn’t be there does not seem to be an uncommon practice, and in any case it’s a pretty minor ethical breach as far as it goes.

Leaving a significant contributor off of the list of authors on an academic paper is much more problematic, for any number of reasons. It’s not just the undisclosed COIs, though that is probably the most important issue. It can also interfere with intellectual property litigation, for example. In academic papers, there really ought never to be any form of ghostwriter.

The question of what constitutes a “significant” contribution is slippery. The ideal is that every author should be responsible for the entire content of a paper, but often publications involve people with non-overlapping expertise who contributed different aspects of the work, and who must accept one another’s contributions based upon trust and reputation.

It seems to me that everybody who provided data, writing, research mentorship, project planning, graphics, useful advice, or editing should be disclosed, but in some cases that may be an acknowledgment rather than authorship.

This is yet more evidence that Orac is a BigPharma shill(tm). Look at all the effort he puts in to ensuring tha BigPharma doesn’t do anything embarrassing. It’s obvious that he just wants to ensure that his employer keeps their reputation.

The controversy goes even further. Some of the journals are supported by the very (pharma) companies that arrange for the ghostwriting that tilts in favor of certain desired outcomes. What is supposed to be an incorruptible source of reliable information has been corrupted by parties seeking favorable influence.

Greed tends to find a way.

I’ve worked with people who were reasonably good thinkers but whose command of English was mediocre. *Someone* had to help them when they wrote papers or poster sessions.

Maybe it’s not ghostwriting if the heavy editing isn’t done by a pro.

Composer99 wins the thread for being the first to notice that Bopiballava won the thread.

since the WHI study was published and HRT use plummeted, the incidence of breast cancer has decreased.

Is there any estimate of the number of excess deaths caused by Wyeth’s promotion of HRT?

I don’t see that the FDA needs any new regulations to go after these ghostwriting pharma companies. If it would be illegal for the company to directly write the off-market piece and send it to physicians with the company name on it, it is just as illegal for the pharma company to write it in secret, lie about who wrote it, pay somebody to dupe the journal editors who then unwittingly print the illegal advertisement. Doing it in secret doesn’t make it “legal”, it just makes it more difficult to get caught.

What the journals should do is go after the pharma company for fraud and charge them full cost for ad space.

The FDA should really hammer these companies for illegally promoting off-market uses. Really hammer them, like triple damages, like fines that exceed the off-market revenues, not profits, revenues.

If the FDA doesn’t do their job, the US is going to end up with a regulatory system like China, where melamine is put into every kind of food.

The AMA could go after the ghostwriting pharma companies in a class-action law suit representing US physicians. Those physicians have clearly been defrauded by those ghostwriting companies. The pharma companies should be compelled to pay for the time the MDs spent reading the ad while thinking it was a legitimate article. 50 hours of wages times 100,000 physicians is enough to fund a real continuing education program in perpetuity.

This is not something to be timid about. Ghostwriting is clearly wrong on so many levels. There is no legitimate excuse for it. This is the kind of case that lawyers always tell their clients to settle because it is a complete no-win situation. What is the marketing manager going to say on the witness stand? I hired these ghostwriters to do in secret what I knew was illegal to do transparently?

Just to clarify: It IS possible for professional medical writers to contribute ethically to the development of academic publications. As another poster pointed out above, written communications might not be a strength of many researchers. At the same time, also stated above, transparency is the key.

The International Committee of Medical Journal Editors puts it very simply: “All persons designated as authors should qualify for authorship, and all those who qualify should be listed.” The American Medical Writers Association subscribes to this criterion, as stated in their Position Statement on the Contribution of Medical Writers to Scientific Publications. Also specified is that all financial relationships should be disclosed.

Following these guidelines can help give readers the information they need to evaluate publications.

For some reason, the combination of the post topic and daedalus2u’s comment on melamine reminds me of the Hungarian paprika scandal when manufacturers were found to be grinding up lead-based paint of an appropriate colour and adding it to their paprika.

Sorry for the off-topic diversion.

I’ve worked with people who were reasonably good thinkers but whose command of English was mediocre. *Someone* had to help them when they wrote papers or poster sessions.

Maybe it’s not ghostwriting if the heavy editing isn’t done by a pro.

I would probably agree that pure editing of prose does not necessarily require a person to be listed as one of the authors… but that’s the exact reverse of what’s happening here. DesignWrite was generating the content and then letting the “author” edit it.

I agree that if you have a colleague or family member or friend to fix your grammar and spelling, that person doesn’t have to be listed.

Orac, Lord Draconis has contacted me and he is most displeased with this post. To say he has his tentacles in knot is an understatement. He says this goes well beyond maintaining cover and is severely detrimental to our secret operations. As a result I have to ask you to return the Ford GT immediately. Also please vacuum out the damn dog hair this time before bringing the vehicle back to us. I will arrange for a *much* less extravagant replacement vehicle.

Axtro Zenicus, Glaxo Pharmbase Fleet Manager

Apologies to Lord Draconis. However, I thought that Lord Draconis understood that occasionally I have to do posts like this to maintain my credibility among the sheeple, so that they are more likely to believe me when I spread our masters’ propaganda. After all, the only reason I tolerate being under deep cover is to accomplish our masters’ bidding.

Apologies to Lord Draconis. However, I thought that Lord Draconis understood that occasionally I have to do posts like this to maintain my credibility among the sheeple, so that they are more likely to believe me when I spread our masters’ propaganda. After all, the only reason I tolerate being under deep cover is to accomplish our masters’ bidding.

Apparently you have not read the new policy requiring that all such credibility posts be sent to Cindy for to be vetted before release. We will allow you to keep the pony. How are it and Bailey getting along?

@ Glaxo Pharmbase Fleet Manager : Axti, please note that I’ve been working my well-manicured, long, delicate fingers to the bone( and I *do* mean that figuratively) acquiring properties, investments, and electronic trinkets for his Lordship, while always spreading the good word about our “little enterprise”, _however_, we are sorely in need of new recruits to do the overlords’ work – I can only provide 7 or 8 foreign exchange students a year ( they don’t grow on trees, you know- again, I don’t mean that literally).Thanks for the “goodies”. Sincerely, DW.

Wow, who knew how corrupt medical journals really were. Doesn’t this poison the well of all medical journal publications? How does one determine the real studies from the ghost-written ones?

I think the academics, the ghostwriters and the directors of Pfizer (Wyeth is a subsidiary) should go to jail over this.

The report in question is a stunning one – the complete assholes even talked about how to use the same strategies they used to cheat in college, to sell people cancer in medical journals.

This whole saga is just itching for a Hollywood retelling. The deep-seated covert ops in a publicly-trusted field just for the pursuit of profit makes this story the clinical equivalent of Jack Abramoff. Pharmaceutical companies are misunderstood capitalists– most of the public, who relies on medical assistance, never questions the motives of these organizations or ever sees them as a the big business that they clearly are.

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