Latest Issue of Bioethics Journal Spotlights Ghostwriting

The current issue of the journal Bioethics focuses on the problem of ghostwriting in the medical literature and is well worth a read. At this point, the main three articles on the topic appear to be free (at least I was able to gain full text access today, and I have no subscription to the journal.)

The first article, by Tobenna D. Anekwe at Harvard School of Public Health, argues that ghostwriting is in fact a form of plagiarism. While ghostwriting is sometimes called "honorary authorship" in order to make it seem acceptable, Anekwe makes the following interesting point:

"Yet honorary authorship is a form of plagiarism
because it entails claiming authorship for work that
was done by others. The twist is that, here, the corporation
(the willing ‘victim’ of plagiarism) actually wants the
scientist to ‘steal’ its work and publish it as his or her
own. But surely this one difference makes industry ghostwriting
no more acceptable. Honorary authorship should
be frowned upon by the research community in the same
way that other types of plagiarism are frowned upon. Yet
it remains unclear from their policies whether universities
view this practice as being as serious as other forms of
plagiarism."

The second article, by Sismondo and Doucet at Queens University in Ontario, describes the insidious process known as "ghost management:"

"In this article, we present evidence that pharmaceutical companies engage in the ghost management of the scientific literature, by controlling or shaping several crucial steps in the research, writing, and publication of scientific articles. Ghost management allows the pharmaceutical industry to shape the literature in ways that serve its interests."

This fascinating trifecta is rounded out by a commentary penned by Carl Elliot and Amy Snow Landa at the University of Minnesota. The authors conclude that both ghostwriting and ghost management are unethical practices and will be difficult to regulate until the medical education companies and physicians who collude with the process feel the sting of litigation:

"Given the amount of litigation against the pharmaceutical industry in recent years, some of which has resulted in record-breaking penalties, it is surprising that no litigation has been directed towards medical writers, medical communications agencies, or the physicians who sign their names to ghosted articles. Maybe this is because these players are seen as mere instruments in a much larger marketing enterprise, or maybe it is simply that their pockets are not as deep. But if a few high-profile lawsuits were successfully aimed in their direction, it is a good bet that the practice of ghostwriting would come to a sudden halt."

Well said.

Thoughts on Ghostwriting

There has been a lively and thoughtful discussion about ghostwriting in the comments section of my post on BlueSpark’s invitation to a doctor to write a review article on bupropion and depression. Here are some of the issues that have come up.

1. What’s in a name?

Michael Altus has been tenacious in his efforts to educate us in the still evolving vocabulary of this business.

“Ghostwriter”= A person who writes or otherwise assists in presenting the author's work without being acknowledged.

“Ghost author” = Identical to a ghostwriter.

“Guest author” = A person who is listed as an author without having made substantial contributions. This is what has also been called “identified author,” or “named author.”

Beyond this, there are acknowledged medical writers, usually listed at the end of an article, and typically described as providing “editorial assistance,” “assistance with data analysis,” etc…. These are not really ghostwriters, because they are visible. However, they are often spectral writers, or semi-ghost writers, because in some cases they have essentially done all the work, including the conception (in conjunction with the company’s marketing team), the outlining, the writing of the first draft, and the final editing. Anybody who does all that, or even part of that, should be listed as an official author. But it doesn’t look very legitimate to have a medical writer without an MD recorded as an author, and what the drug companies are looking for is legitimacy, whether genuine or fabricated.

2. So who should be listed as an “author”?

According to the web site of the International Committee of Medical Journal Editors (ICJME), in order to get your name up in lights as an author of a scientific paper, there are three specific criteria. To quote from their recommendations:

“Authorship credit should be based on 1) substantial contribution to conception and design, acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published.”

As you can see, there’s quite a bit of wiggle room here. For example, what should count as “substantial contribution to conception”? If an academic has a brief phone conversation or an email exchange with a pharma-funded medical writing firm in which the topic of the article is discussed, the firm might later argue that this counted as a “substantial contribution to conception.” In fact these criteria do not require that an author do any actual writing—as long as they do some “revising.” As an editor myself, I know that “revising” is an expandable term, and can include everything from reading a draft of an article and saying “that looks great, I have no changes for you,” all the way to performing major surgery on the very organization of a paper.

3. Isn’t ghostwriting acceptable in some circumstances?

This is really the crux of the controversy about ghostwriting. Many commenters have pointed out that making science understandable is difficult, specialized work. It is unrealistic to think that scientists have the time or expertise to do the wordsmithing needed.

I agree, which is why I draw a bright line between industry-funded medical writing and academia-funded medical writing. Both ghostwriting and acknowledged editorial assistance are perfectly acceptable when the assistance is not arranged by a company that has a stake in the topic of the article. Most academic departments hire research assistants and editors whose jobs are to help write the many articles that get churned out by the more productive members of the departments. There is no incentive for such editors to bias the articles in any way.

But when an editor is paid, either directly or indirectly, by a drug company to work on an article, readers should be concerned, because now there is a powerful incentive for the editor to manipulate the content of the article to promote the sponsor’s product. If the final published article is not promotional enough, the writer won’t get a future assignment from the funding company. It’s as simple as that.

4. What’s the solution?

I have two recommendations:

--Journals should not publish articles that are clearly written in order to promote the funder’s product. Generally speaking, this would exclude any articles involving medical writing companies, even when their involvement is acknowledged. After the many recent example of corrupted scientific literature by drug company/medical writing firm partnerships, we can no longer have any trust that such teamwork is anything other than marketing.

--Journals should continue to publish research funded by industry, as long as the researchers sign disclosure statements assuring editors that they had complete control and involvement in every aspect of the paper. This means essentially no contact with the drug company after having accepted the money. Obviously, such research can still be highly tainted by bias, but the degree of bias is likely to be less extreme. Furthermore, as the medical literature gate-keepers, editors will scrutinize such research with extra care in order to make sure they are not unwittingly publishing advertisements in guise of science.

Subject: Invitation to Author a Review Article

Here is an email sent to one of my psychiatrist colleagues by BlueSpark, a medical communications company working under contract for the drug company sanofi-aventis. Read it, and decide whether you think this is a solicitation to become a ghost author.

Subject: Invitation to Author a Review Article
Date: Dec 2009

Dear Dr. XXXXXXX,

I hope this note finds you well. My name is Jonathan Wert, MD, and I am a medical director at BlueSpark Healthcare Communications, a medical communications company located in northern New Jersey. I was given your contact information by Dr. YYYYYYY , who spoke very highly of you.

I am writing to you on behalf of sanofi-aventis, which has authorized us to facilitate publication of an MDD/Bupropion-focused review article. We feel that your input on a multitude of topics including the following would be extremely valuable:

* Your views on MDD, including the variability in response to treatment.
* How MDD is currently being treated and how successful these treatments are at inducing remission and preventing relapse.
* What are the other benefits of available therapies?
* What are the unmet needs/drawbacks of these medications?
* What attributes novel antidepressants should have.

sanofi-aventis and BlueSpark would be pleased to have you serve as the author of this article, and we will work closely with you in its development. Initially we will help develop a draft outline. Once you have reviewed and approved this outline, we will proceed to development of a draft paper. We will then revise the manuscript according to your direction and assure that it is styled appropriately for submission to your proposed journal.

As I am sure you are very busy, our team would like to arrange a brief conference call to discuss the content to be included in the manuscript/outline. I look forward to hearing from you at your earliest convenience.

Best regards,
Jon

Jonathan M. Wert, MD, MAAP

Here’s the way I interpreted the letter.

Sanofi-aventis just introduced a “new” antidepressant called Aplenzin. Aplenzin is not really new at all, being simply a reformulated version of bupropion extended release. Its advantage is that it offers once a day dosing in all three of the usual doses prescribed (150 mg, 300 mg, and 450 mg), whereas generic bupropion ER offers once daily dosing for 150 mg and 300 mg only. The unusual patient who needs 450 mg dose has to combine 150 mg with 300 mg. So from a clinical standpoint, Aplenzin represents an “advance” in the most minutely incremental sense.

The disadvantage of Aplenzin is not so subtle. It is a health care budget-buster, costing 20 times more than generic bupropion ER. Where do I get this figure? Vermont’s Pharmaceutical Marketer Price Disclosure Law requires that drug companies disclose their drug’s wholesale price along with the prices of drugs in the same class. It turns out that the starting dose of Aplenzin costs $5.58, while the same dose of generic Bupropion ER costs only 28 cents. I’m sure Obama would be pleased to hear about this!

Obviously, selling Aplenzin is going to be an uphill battle, so along with the usual journal ads and drug rep visits, sanofi-aventis has added a publication plan to their marketing strategy. Here’s where Dr. Wert and BlueSpark come in. BlueSpark is looking for doctors to write, as they put it, an “MDD/Bupropion-focused review article.”

Although the letter is artfully crafted to make it appear that they are simply seeking the good doctor’s “input” on some issues, the flavor of input they are after is clear if you read between their lines. I’ve taken the liberty of deciphering the coded language used by BlueSpark, in order to further clarify the nature of their solicitation.

* “Your views on MDD, including the variability in response to treatment.”
[You should say that lots of patients don’t respond to SSRIs or to the usual doses of bupropion, in order to set up the conclusion that Aplenzin is useful.]

* “How MDD is currently being treated and how successful these treatments are at inducing remission and preventing relapse.”
[Here, your focus will be on how SSRIs are often not successful at achieving remission, so you better try Aplenzin.]

* “What are the other benefits of available therapies?”
[Similar to the point above, namely, say that available therapies suck, so hurray for Aplenzin].

* “What are the unmet needs/drawbacks of these medications?”
[The main drawback: nobody is prescribing Aplenzin yet]

* “What attributes novel antidepressants should have.”
[Best attribute: be a once a day version of bupropion like Aplenzin].

Playing fair, I emailed Dr. Wert, telling him that this looked to me like a solicitation for a ghost author, which is contrary to the policies of the International Committee of Medical Journal Editors, and asking him if he wanted to comment.

I got a response from Michael Weems, BlueSpark’s COO, who disagreed with my assessment, saying that I had “misunderstood” his invitation: To quote from his response: “Any development of a draft manuscript would take place only after the author has developed a formal outline that would include tables, figures, and references. Following this, the author would review the draft manuscript and have total control of the content (ie., change, add, remove, or edit as he or she sees fit to meet the manuscript objectives). Our role would be to facilitate the development of the article by helping the author publish the article in a timely fashion. Additionally, our support is always acknowledged and can also lead to co-authorship if it meets the guidelines defined by the ICJME.”

As I read Mr. Weems’ letter, my built-in BS detector went as wild as a Geiger counter in Iran. Because let’s face it. No psychiatrist is going to wake up in the morning and say, “I think today is the day I’ll work on a review article on bupropion and depression and how awful it is that the tiny number of patients who require the maximum dose have to take two pills in the morning instead of one. Yes—this will be a significant contribution to the medical literature.”

This would never happen, because there’s nothing new or interesting in this topic. We know that bupropion works well for depression, and we’ve known it even since it was approved by the FDA in 1985.

No, the only reason a psychiatrist would get motivated to write such an article is if a cold-call email solicitation from BlueSpark gets past the spam filter. I’m guessing that BlueSpark hopes that eventually they will find an uncreative, mid-level academic who is treading water professionally, and who will jump at the chance to pocket a little extra money while simultaneously padding the resume with a publication that will require essentially no work to produce. (Dr. Wert’s line at the end of his solicitation, “As I am sure you are very busy…” seems a nudge-nudge wink-wink assurance that the company will take care of everything.)

Whether or not this meets the formal definition of ghost-writing, it is clearly a manipulation of the medical literature, a kind of plastic surgery of science. The articles may look impressive, and they may look real, but in fact they will be phony.

The most telling part of BlueSpark’s response to me came at the end of the COO's letter:

“Based on your misunderstanding of our invitation, we are requesting that you do not post this letter on your blog. If you have any additional questions or would like to discuss this topic further, please e-mail me or call me directly at the number below.”

Does this mean that if I had understood the invitation, they would have been happy to see it posted? I doubt that. Or was this simply BlueSpark’s effort to bully me into keeping this embarrassing letter out of the public eye? If so, I guess it didn't work.

Abe Lincoln put it well: “You can fool some of the people all of the time, and all of the people some of the time, but you cannot fool all of the people all the time.” For all of our sake, let’s hope this holds as true in the 21st century as it did in the 19^th.

Ghostwriting Stays in the Spotlight

With Natasha Singer's article on ghostwriting appearing in the Health section of today's New York Times, this underhanded method of drug promotion is in the public spotlight as never before. Medical ghostwriting leaches out the confidence we have in the authenticity of medical research, because the articles are conceived and written by drug company marketers and their surrogates. But when they are published in the top journals, they look like serious reports of medical science, complete with the names of prestigious doctors who are dubbed "authors."

After you read the New York Times article, I suggest you read this very clever article by William Heisel, a two time Pulitzer finalist, who blogs on Reporting on Health, a project of the Annenberg School for Communication at USC. Heisel's focus is on the self-deluded ways doctors are rationalizing their partipation in medical ghostwriting. For example, Dr. Leon Speroff, a former professor of obstetrics and gynecology at Oregon Health Sciences University who allowed DesignWrite to put his name on a paper he didn't write, defended his bad behavior by saying that it was then "standard practice" to not disclose a drug company's involvement.

Comments Heisel:

Why is it when these researchers are caught with a drug company's hand playing them like a puppet, they pull the "standard practice" line? Standard for whom? Certainly not for the patients taking the pills and presumably not for the journal editors accepting the articles for publication. Perhaps this is something Sen. Charles Grassley, R-Iowa, should ask in a hearing. Speroff told the Journal Sentinel he had nothing to apologize for:

"There is nothing dishonest about it."

Speroff was quoted in this excellent investigative report on medical ghostwriting at University of Wisconsin written by--who else?--the incomparable John Fauber and Meg Kissinger of the Milwaukee Journal Sentinel, both of whom should be on the short list at the next awards meeting of the Pulitzer committee.

Ghostwriting for Premarin: Steroids on Steroids

Today's New York Times reveals the not particularly astonishing fact that Wyeth Pharmaceuticals engaged a medical writing company to produce 26 articles pushing Premarin as Hormone Replacement Therapy (HRT) in women from 1998-2005. The articles were outlined and written by writers employed by Design Write, and then were sent to top academics in the Ob/Gyn field, who reviewed them, rubber stamped them with occasionally minor edits, and submitted them to journals under their names. In no case was Wyeth's involvement in funding the articles disclosed.

We've heard this sordid tale before. Last year, an article in JAMA revealed that Merck commissioned ghostwriters to produce dozens of articles pushing Vioxx (see the NY Times coverage here--you'd need a subscription to JAMA to read the original paper by Joseph Ross); Eli Lilly paid ghostwriters to push Zyprexa; and Pfizer-funded ghostwriters generated the majority of articles about Zoloft in the late 1990s, according to the British Journal of Psychiatry.

What to make of all this? The best analysis I've heard yet was provided by Dr. Joseph Ross of Mt. Sinai Hospital in New York, who was quoted in today's paper:

“It’s almost like steroids and baseball,” said Dr. Joseph S. Ross, an assistant professor of geriatrics at Mount Sinai School of Medicine in New York, who has conducted research on ghostwriting. “You don’t know who was using and who wasn’t; you don’t know which articles are tainted and which aren’t.”

In this case, since Premarin is a steroid, Wyeth put its own steroids on steroids. As with baseball players on steroids, when companies pour marketing money into ghostwriting campaigns, they change the rules of the academic game. The playing field is no longer level; the drug company's version of the truth gains the upper hand. Sometimes, their truth really is the truth, but sometimes it's a carefully crafted lie. Sorting it out is difficult even for physicians who specialize in the area being written about. It's essentially impossible for the average generalist physician, to say nothing of patients who did not have the advantage of attending medical school.

As the New York Times article says, some journals now require that all authors detail precisely who wrote what and who was paid by whom before considering manuscripts. It is time for all journals to institute this policy. In addition, several academic medical centers now forbid their faculty from engaging in ghostwriting, a trend that will continue.
As I've said before, it would be nice if those who are caught with their hands in the cookie jar would have the courage to apologize. But nobody involved in this latest scandal is willing to so. Design Write, the company that did Wyeth's dirty work, said that:

[the company ] “has not, and will not, participate in the publication of any material in which it does not have complete confidence in the scientific validity of the content, based upon the best available data.”

Dr. Gloria Bachmann, a professor of Ob/Gyn who rubber stamped an article pushing Premarin for hot flashes and other symptoms, said:

“There was a need for a review article and I said ‘Yes, I will review the draft and make sure it is accurate,’ ” Dr. Bachmann said in an interview Tuesday. “This is my work, this is what I believe, this is reflective of my view.”

And Wyeth's spokesman said that "the articles on hormone therapy were scientifically sound and subjected to rigorous review by outside experts on behalf of the medical journals that published them."

Actually, the proper collective response from all of these participants should have been: "We sincerely apologize for having deceived the medical community by engaging in ghostwriting without disclosure. We have contributed to the erosion of the public's trust in medicine, and we regret it."