Princess Health and The Reappearance of a Ghost of Seasons Past. Princessiccia

Princess Health and The Reappearance of a Ghost of Seasons Past. Princessiccia

Actonel conflicts of interest ghost writing manipulating clinical research Procter and Gamble suppression of medical research University of Sheffield whistle-blowers

Gusty 08:01 Add Comment

About a year after we started Health Care Renewal, in late 2005, we wrote multiple posts about the complex and unfortunate case of Dr Aubrey Blumsohn's attempts to keep a research project honest. The early posts were here, here, here, and here. In this post, we summarized the case thus:

• Dr Aubrey Blumsohn, a senior lecturer at Sheffield University, and Professor Richard Eastell performed a research project on the effects of the drug risedronate (Actonel, made by Procter & Gamble Pharmaceuticals [P&G]) under a contract between P&G and the University.
• Although the research contract designated Blumsohn and Eastell as "Investigators" under whose direction the project would be carried out, Blumsohn was not given access to the original data collected by the project.
• Despite numerous requests, (like this one), P&G refused access to this data repeatedly.
  Blumsohn was concerned that he and Eastell could be accused of scientific fraud if they continued to make presentations and write articles and abstracts without access to the data which they were supposedly writing about.
• Blumsohn became suspicious that some of the analyses done by P&G could be misleading, especially related to a graph shown to him that omitted 40% of patient data.
• Blumsohn objected to P&G arranging for papers and abstracts to be written by a professional writer, but with Blumsohn listed as first author. Blumsohn was concerned that such ghost-written documents were mainly meant to convey "key messages" in support of P&G's commercial interests.
• Eastell warned Blumsohn not to aggravate P&G, because the company was providing a grant to the University which "is a good source of income."
• After repeated failed attempt to get the data, Blumsohn complained to numerous officials at Sheffield University, including Eastell, medical school Dean Tony Weetman, University Vice-Chancellor Robert Boucher, and the Head of the University's Department of Human Resources, Ms R Valerio.
• Still unable to get the data, he spoke with news reporters about his case. At this point, Sheffield suspended him, but then offered him a severance agreement if he signed a contract binding him not to make any detrimental or derogatory statements about the University and its leaders.

So the case involved suppression and manipulation of research, ghost-writing, institutional conflicts of interest, and attempts to silence a whistle blower. It provides lessons about the downsides of letting commercial firms sponsor and hence control human research designed to evaluate the products or services they sell; and of academic medicine becoming dependent on research money from such firms for such research. Although Health Care Renewal, being US based, most often writes about such issues in the US, this case is a reminder that they are global. (Note that we posted more about this case in 2006, here, here and here, but since then it has not gotten much public attention.)

Last weekend the (UK) Guardian returned to it:

The Guardian has learned that one of Britain's leading bone specialists is facing disciplinary action over accusations that he was involved in 'ghost writing'.

The General Medical Council will call Professor Richard Eastell in front of a fitness to practice committee. Eastell, a bone expert at Sheffield University, has admitted he allowed his name to go forward as first author of a study on an osteoporosis drug even though he did not have access to all the data on which the study's conclusions were based. An employee of Proctor and Gamble, the US company making Actonel, was the only author who had all the figures.

Experts believe the practice is widespread in Britain.

In a letter published in the Journal of Bone and Mineral Research, which carried the original study, he stated: 'In the original paper one of the authors, a statistician working for P&G, Ian Barton, had full access to all the data.' The authors had full access to all the analyses of the data that they requested, he said � but those analyses were carried out by the company.

The letter, published in 2007, also acknowledged flaws in the study. A later independent analysis of the data 'identified some errors and poor practice', he wrote. The study was designed to show the strengths of Actonel which was in fierce competition with a rival bone-strengthening drug called Fosamax, made by Merck.

Eastell's paper concerned a study carried out on behalf of Proctor and Gamble, comparing the bone density of women prescribed Actonel with others who were not. Only the company knew which women were on the drug and which were taking something else.

Eastell's colleague, Dr Aubrey Blumsohn, wanted the codes which would say which of the patients who suffered fractures had been on the drug. The company refused. Blumsohn took his concerns to Eastell, but in a conversation which Blumsohn says he taped , Eastell said he was concerned that persistent requests might damage the relationship they had with the company. Eastell is said to have told him: 'The only thing that we have to watch all the time is our relationship with P&G. Because � we have the big Sheffield Centre Grant [from P&G] which is a good source of income, we have got to really watch it.' .

So, after four years, this case has generated an official hearing of sorts. The hearing is obviously late, and seemingly will only be devoted to only one aspect of this case (ghost writing). However, at least our friends in the UK are doing something. I cannot recall a single case that resulted in any serious consideration of imposing negative consequences on anyone who was accused of suppressing research, manipulating research, endorsing ghost-writing, or intimidating a whistle-blower. In fact, many of the more troubling cases have never resulted in any sort of public discussion either at the institutions at which they occurred, or at any organization with relevant regulatory, or even just moral authority. So the GMC hearing is at least a step forward. Two cheers for the British GMC, and none for US universities, academic medical centers, professional societies, and government regulators.

(If anyone can remind me of a case in which there was a public discussion at the relevant institution, or some public consideration of the case by a regulatory agency, professional society, or some group with moral authority, please remind me of it, and I would be happy to post about it.)

Princess Health and Wyeth, Ghostwriting, Dr. Joseph Camardo and a Big Liquor Store With a Little Grocery Department. Princessiccia

Princess Health and Wyeth, Ghostwriting, Dr. Joseph Camardo and a Big Liquor Store With a Little Grocery Department. Princessiccia

ghost writing health care ethics Wyeth

Gusty 06:32 Add Comment

Ghostwriting is a topic covered extensively at Healthcare Renewal, including at my post "Wyeth: Ghostwritten Papers Fake, But Accurate" here, Roy Poses' "Wyeth's Industrial Scale Ghost-Writing" here, and many others about Wyeth and other pharmas that can be viewed via this link: http://hcrenewal.blogspot.com/search/label/ghost writing.

A story in the Philadelphia Inquirer yesterday about Wyeth and ghostwriting brought to mind my medical school days at Boston University, in a metaphorical and rather negative way, regarding an oddity reflecting today's pharma industry.

In those years I lived next to Boston City Hospital on the top floor of a 29-story high rise at 35 Northampton Street, at that time one of the toughest and highest crime neighborhoods in the region if not the country (I was careful and lucky, and only got mugged at gunpoint once.) I had an excellent bird's-eye view of the urban decay in the area, reflective of ethical decay in the community.

35 Northampton St., next to Boston Medical Center (formerly Boston City Hospital)

Across the street from the high rise was an oddity - a very large liquor store named Blanchard's. Inside Blanchard's was a very small grocery department of all things. Have a snack with your booze! (I went in only twice; once to see what it was all about, and again during the Blizzard of '78 to get some needed food when all transit in the city was shut down and several feet of snow -- and neighborhood guns -- inhibited foot travel.)

The area has much improved in the past three decades, but according to Google street view the liquor store is still there:

In the 1970's "Liquor Land" was a large liquor store with a small grocery department named "Blanchard's." Click to enlarge.

Why does this odd store remind me of Wyeth, and more generally today's pharmaceutical industry?

Because that industry has turned from what used to be a biomedical research & development industry with decent ethics and a small marketing arm, to large marketing industry with poor ethics and a small R&D arm.

(Or, perhaps more accurately, a large marketing industry with poor ethics and a busywork section disguised to look like R&D. As a colleague noted in my post "Pfizer/Wyeth Merger And Sacrificing The Future: Laying Off Scientific Staff All Over The Place" here, a small fraction of prime scientist intellectual horsepower and time is actually spent on true R&D today, the rest wasted on feeding the bureaucratic corpulence that is the modern pharma research lab. He observed that "what we today call pharmaceutical R&D is in reality busywork disguised to look like R&D, in effect a well engineered, well managed, massively expensive failure.")

Here is what led to my "pharmas have become large marketing firms with a small R&D effort" metaphor. It was a story in the local newspaper on ghostwriting.

The glib quotes from Dr. Joseph Camardo, Wyeth's senior vice president of global medical affairs, on the practice of ghostwriting are simply stunning:

Philadelphia Inquirer

Ghosts in the medical machine

Was drug research infected by ghostwriters? With Paxil suit in court, a Chadds Ford firm says it was ethical.

Sun, Sep. 20, 2009

By Miriam Hill

Inquirer Staff Writer

When GlaxoSmithKline P.L.C. marketers looked for doctors to promote the antidepressant Paxil, they called the project CASPPER. The name was more than just an offbeat tribute to the friendly cartoon ghost. It was a wink and a nod to "ghostwriting," a questionable practice in which scientists put their names on research written by someone else, usually a writer paid by a drugmaker.

Ghostwriting critics say it disguises marketing material as scientific research.

Charges of ghostwriting have been lobbed against many companies in recent years, including Glaxo, Wyeth, AstraZeneca P.L.C., and Merck & Co. Inc., often arising in lawsuits from consumers claiming a drug hurt them.

... Documents released in connection with 8,000 lawsuits filed against Wyeth over Premarin and Prempro show that the company, which employs several thousand people in Collegeville, paid a medical-writing firm to produce articles from 1998 to 2005 that allegedly downplayed the risks of hormone treatment and emphasized benefits.

In 2002, researchers stopped a landmark federal study after finding that menopausal women who took certain hormones had an increased risk of breast cancer, heart disease, and stroke.

"Ghostwriting was used to sway physician opinions to favor hormone use as disease prevention long after that was a scientifically defensible position," Fugh-Berman [writer Adriane Fugh-Berman - ed.] said.

Joseph Camardo, Wyeth's senior vice president of global medical affairs, called Fugh-Berman's view "baseless." Medical opinion evolves, he said, and the papers in question reflected scientific understanding then. He also said the authors alone controlled the content and writing of the papers, though some did have outside help paid for by Wyeth.

"It's really being misrepresented as something we wrote and paid for that said what we thought it should say," Camardo said. "But the authors were not paid, and the authors had the final say."

... Studies on ghostwriting have suggested that anywhere from 8 percent to 75 percent of articles in medical journals may involve the practice.

Aside from the point I raised in my post "Has Ghostwriting Infected The Experts With Tainted Knowledge, Creating Vectors for Further Spread and Mutation of the Scientific Knowledge Base?" here regarding possible severe contamination of the literature and therefore of "expert knowledge" as it exists today, Camardo's response raises a cornucopia of questions.

Regarding "Medical opinion evolves, he said, and the papers in question reflected scientific understanding then":

• Whose scientific opinion do they reflect, exactly?
• Does Camardo believe these ghostwritten papers, usually written by party "A" but with authorship claimed by party "B" (usually prominent academic physicians often nurtured by the industry into the role of "key opinion leaders", KOL's) are objective?
• Does Camardo actually believe most of the content comes from party "B" rather than party "A" in these papers?
  
• Does Camardo understand that paying a MECC (Medical education & communications company) or other firm to write scientific papers puts the author(s) of those papers in a conflict of interest position relative to the paying sponsor, injurious to objectivity?
• Is Camardo that naive to believe a paid writer would "diss" the holder of his or her paycheck?

Regarding "the authors alone controlled the content and writing of the papers, though some did have outside help paid for by Wyeth":

• Which authors is he referring to?
  
• The ghostwriters?
• Wyeth scientists?
• Academics claiming authorship?
  
• Was the "outside help" from Wyeth "authors" to the ghosts, or from the ghosts to Wyeth "authors", or from Wyeth to the academics claiming authorship, or what?
• Can Camardo produce statistics on what % of article content on ghostwritten articles Wyeth sponsored were written by the ghost vs. written by Wyeth scientists and/or the claimed academic author? If not, why not? And if not, why should any intelligent person not assume the papers are, say, 99% the product of the hired guns?

Regarding "the authors were not paid, and the authors had the final say":

• Again, which author(s) is he referring to?
• In terms of the ghosts, I assume they were not working for the MECC's for free.
• In terms of the academics and KOL's claiming authorship, they (maybe!) were not paid in money, but instead in the valuable academic currency of a publication in a major biomedical journal.
  

To claim the KOL's were "not paid" is disingenuous. In fact, I find his entire argument disingenuous, a play on words, PR "spin" completely callous to the needs for scientific objectivity, the advancement of science, and ultimately to patient's lives.

This is marketing, with poor ethics, in the extreme.

Being somewhat familiar with authorship issues as former Director of Published Scientific Information Resources and The Merck Index (of Chemicals, Drugs & Biologicals), 13th ed. at Merck Research Labs, I further pointed out in my post "Wyeth: Ghostwritten Papers Fake, But Accurate" here, that:

... in addition to the violation of accepted practices of authorship, such as specified by NIH and the International Committee of Medical Journal Editors, among others, such lucky authors [i.e., those who claim authorship of ghostwritten papers] get to "count" such papers in their academic portfolios, presumably also in violation of their own institutional policies and guidelines for fair attribution and intellectual honesty, e.g., here [Harvard - ed.]

These industry practices and Camardo's position may be based on:

• Ignorance of accepted practices of authorship of the NIH, the International Committee of Medical Journal Editors, and most academic institutions, or perhaps:
  
• Cavalier dismissal of these practices for pecuniary reasons.

Is Camardo informed and upfront? Inept? Disingenuous and dishonest? That is up to the reader to decide.

In my aforementioned post "Wyeth: Fake but Accurate" I'd also noted Wyeth attorney Stephen Urbanczyk acknowledging that the ghostwritten articles were part of a marketing effort. But he said that they were also "fair, balanced, and scientific." More spin.

This raises the following observation. It is said that you can judge people by the company they keep. I also believe that:

You can judge companies by the people they keep.

This raises the following very serious questions:

• Is the presence of a senior vice president of global medical affairs and a lawyer with such views on ghostwriting representative of the senior executive leadership's views on dissemination of biomedical scientific information?
  
• Is their presence reflective of the views of Wyeth's Board of Directors?

If so, then the objectivity of any article about Wyeth drugs is called into question, and physicians and patients should utilize Wyeth drugs (and literature on them) with great caution.

-- SS

Addendum: this from the Medical Ethics blog:

Recently released court documents in a lawsuit against drug giant Wyeth, thanks to a court action by the New York Times and PLoS Medicine, are now searchable at a University of California, San Francisco web site.

The Wyeth documents are the latest made searchable at the Drug Industry Document Archive, or DIDA, which archives the documents from several high-profile cases.

... The documents were first made available last month on the PLoS web site, but were not searchable and difficult to sort through. The DIDA site now make it possible to search for documents by name, type or content.

Also see "Ghostwriting: Why they do it" at that blog.

-- SS

Princess Health and Medical Whistleblowers' Roundtable. Princessiccia

Princess Health and Medical Whistleblowers' Roundtable. Princessiccia

data manipulation ghost writing mission-hostile management whistle-blowers

Gusty 11:48 Add Comment

PLoS Medicine just published a summary of a round-table discussion by notable whistleblowers about pharmaceutical companies' research and marketing practices, with an accompanying editorial. (The on-line journal stepped in as a sponsor 10 days before the conference, after the unnamed journal that originally was going to sponsor the meeting pulled out on its lawyers' advice.)
The conference underlined some of the issues that have appeared on Health Care Renewal. Some notable quotes:

• Betrayal of Mission: According to David Graham (who raised concerns about the safety of Vioxx), The US Food and Drug Administration (FDA) is in a "collaborative relationship" with pharmaceutical companies. A senior FDA official told Graham, "industry is our client." The public may be excused for thinking that they are supposed to be the FDA's clients.
• Tactics to Increase Likelihood of Favorable Results: Several participants talked about specific tactics used by some pharmaceutical companies to increase the likelihood that research results will be favorable to their products. An anonymous industry scientist noted that it takes only two positive studies to get FDA approval. But if a study has bad results, "typically a company is not going to publish the study at all." Furthermore, he said "drug companies assiduously avoid acquiring information about side effects." Patients who have increased risks of side-effects "are excluded from studies deliberately, even though, when the drug is approved, these patients will be targeted for sales." He also charged that studies are deliberately designed to be too small, or be over too quickly to detect serious adverse effects.
• Conflicts of Interest: Several participants suggested how drug companies convey money to public officials to influnce state level decisions about drugs. One charged that officials who were responsible for writing state guidelines about psychiatric treatments could access a secret account financed by drug companies. He was told, "Look, drug companies write checks to politicians, they write checks to politicians on both sides of the aisle - back off." He was then advised, "quit being a salmon, swimming against a stream."
• Ghost-Writing: The anonymous industry scientist described the process of ghost-writing, "When studies are published, they are frequently written not by the trained research scientist, who might have designed and analyzed the study, but by a designated medical writer with little if any backgroun in research, but who is trained instead to craft the findings of the study in the best possible way for the company."

This is important additional evidence about how deep these problems run. Solving them will take a lot of salmon.

Princess Health and Medical Whistleblowers' Roundtable.Princessiccia

Princess Health and Medical Whistleblowers' Roundtable.Princessiccia

data manipulation ghost writing mission-hostile management whistle-blowers

Gusty 11:48 Add Comment

PLoS Medicine just published a summary of a round-table discussion by notable whistleblowers about pharmaceutical companies' research and marketing practices, with an accompanying editorial. (The on-line journal stepped in as a sponsor 10 days before the conference, after the unnamed journal that originally was going to sponsor the meeting pulled out on its lawyers' advice.)
The conference underlined some of the issues that have appeared on Health Care Renewal. Some notable quotes:

• Betrayal of Mission: According to David Graham (who raised concerns about the safety of Vioxx), The US Food and Drug Administration (FDA) is in a "collaborative relationship" with pharmaceutical companies. A senior FDA official told Graham, "industry is our client." The public may be excused for thinking that they are supposed to be the FDA's clients.
• Tactics to Increase Likelihood of Favorable Results: Several participants talked about specific tactics used by some pharmaceutical companies to increase the likelihood that research results will be favorable to their products. An anonymous industry scientist noted that it takes only two positive studies to get FDA approval. But if a study has bad results, "typically a company is not going to publish the study at all." Furthermore, he said "drug companies assiduously avoid acquiring information about side effects." Patients who have increased risks of side-effects "are excluded from studies deliberately, even though, when the drug is approved, these patients will be targeted for sales." He also charged that studies are deliberately designed to be too small, or be over too quickly to detect serious adverse effects.
• Conflicts of Interest: Several participants suggested how drug companies convey money to public officials to influnce state level decisions about drugs. One charged that officials who were responsible for writing state guidelines about psychiatric treatments could access a secret account financed by drug companies. He was told, "Look, drug companies write checks to politicians, they write checks to politicians on both sides of the aisle - back off." He was then advised, "quit being a salmon, swimming against a stream."
• Ghost-Writing: The anonymous industry scientist described the process of ghost-writing, "When studies are published, they are frequently written not by the trained research scientist, who might have designed and analyzed the study, but by a designated medical writer with little if any backgroun in research, but who is trained instead to craft the findings of the study in the best possible way for the company."

This is important additional evidence about how deep these problems run. Solving them will take a lot of salmon.

Princess Health and Media Reports on How Pharmaceutical Companies May Manipulate Information. Princessiccia

Princess Health and Media Reports on How Pharmaceutical Companies May Manipulate Information. Princessiccia

clinical trials direct to consumer advertising ghost writing pharmaceuticals

Gusty 14:15 Add Comment

Newspapers have become interested, again, in the issue of pharmaceutical companies manipulating information supplied to the public or health care professionals.

USA Today published several stories on the pharmaceutical industry. One was on various tactics the industry may used to mislead the public in television direct to consumer advertising, according to the US Food and Drug Administration (FDA). These included:

• Overstating the effectiveness of a drug. For example, a Novartis ad included graphics that implied, according to the FDA, Lamisil is completely effective in eradicating nail fungus. The FDA asserted, in contrast, that clinical trials only revealed a 38% cure rate.
• Advertising a drug for problems other than those for which its use was approved by the FDA. For example, Wyeth advertised Effexor as treatment of mild depressive symptoms, according to the FDA. The drug, however, was only approved by the FDA for major depressive disorder.
• Unsubstantiated claims. For example, Hoffman-La Roche advertised Xeloda, a cancer chemotherapy agent, using testimonials that the drug didn't make patients "too tired" or "too sick." However, the FDA noted "in stark contrast" the number of reports that Xeloda makes people feel sick and tired.

USA Today also ran a story on how pharmaceutical companies may ghost-write articles, and then try to get academics to pose as first authors. (Our last posting on ghost-writing is here, and a posting about how medical schools are willing to sign contracts with research sponsors that allow the sponsors to write up research results, is here.) It included an estimate by Dr. Martha Gerrity, Co-Editor of the Journal of General Internal Medicine, that two to four of the 70-80 manuscripts the journal receives each month may be ghost-written. Dr. Catherine DeAngelis, the Editor of the Journal of the American Medical Association said that before she became an editor, she got one phone call a month asking her to pose as the author of a ghost-written article. The article provides another bit of evidence that ghost-writing may be far more prevalent than most physicians and researchers realized. Yet, as Dr. DeAngelis said, ghost-writing is "manipulation by for-profits to alter what's in the (medical) literature so that they could sell their products."
Finally, the NY Times ran a story suggesting that pharmaceutical companies seem split about whether to submit information to online registries of controlled trials. These registries had been proposed as a way to prevent the companies from hiding unfavorable results of clinical trials.
Some companies, notably Eli Lilly, have apparently been quick to provide trial information to the registries. Dr. Alan Breier, the company's chief medical officer, said "fundamentally, what we're doing is in the interest of patients, and I think that this is the winning model, for academia, for industry, and the future."
On the other hand, some companies, e.g., Merck, Pfizer, and GlaxoSmithKline, have been stingy in the information they have provided to the NIH clinical trials registry, clinicaltrials.gov. Dr. Deborah Zarin, the director of the site, noted, for example, that Merck only said that one trial was a "one-year stury of an investigational drug in obese patients." Failing to provide crucial details, like the name of the drug, would make it impossible in the future to tell if Merck ever published a report of the trial's results.
The Times reported that "executives and press representatives at the companies said generally that disclosing too much information about early-state trials might reveal business or scientfic secrets." On the other hand, Dr. Breir of Lilly felt that it could supply information to the registry while still protecting its intellectual property.
In summary, physicians' efforts to make decisions for patients based on the best available research data are frustrated when companies hide or manipulate research results which put their products in a bad light. Manipulating or hiding research results betrays those patients who volunteered to participate in clinical trials intending to help advance science and improve patient care. Misleading advertising pushes patients to get treatments that are needlessly expensive, and sometimes needlessly hazardous. Too often, pharmaceutical companies seem to have forgotten their high-minded promises to help patients with better treatments in the pursuit of short-term profits.

Princess Health and Media Reports on How Pharmaceutical Companies May Manipulate Information.Princessiccia

Princess Health and Media Reports on How Pharmaceutical Companies May Manipulate Information.Princessiccia

clinical trials direct to consumer advertising ghost writing pharmaceuticals

Gusty 14:15 Add Comment

Newspapers have become interested, again, in the issue of pharmaceutical companies manipulating information supplied to the public or health care professionals.

USA Today published several stories on the pharmaceutical industry. One was on various tactics the industry may used to mislead the public in television direct to consumer advertising, according to the US Food and Drug Administration (FDA). These included:

• Overstating the effectiveness of a drug. For example, a Novartis ad included graphics that implied, according to the FDA, Lamisil is completely effective in eradicating nail fungus. The FDA asserted, in contrast, that clinical trials only revealed a 38% cure rate.
• Advertising a drug for problems other than those for which its use was approved by the FDA. For example, Wyeth advertised Effexor as treatment of mild depressive symptoms, according to the FDA. The drug, however, was only approved by the FDA for major depressive disorder.
• Unsubstantiated claims. For example, Hoffman-La Roche advertised Xeloda, a cancer chemotherapy agent, using testimonials that the drug didn't make patients "too tired" or "too sick." However, the FDA noted "in stark contrast" the number of reports that Xeloda makes people feel sick and tired.

USA Today also ran a story on how pharmaceutical companies may ghost-write articles, and then try to get academics to pose as first authors. (Our last posting on ghost-writing is here, and a posting about how medical schools are willing to sign contracts with research sponsors that allow the sponsors to write up research results, is here.) It included an estimate by Dr. Martha Gerrity, Co-Editor of the Journal of General Internal Medicine, that two to four of the 70-80 manuscripts the journal receives each month may be ghost-written. Dr. Catherine DeAngelis, the Editor of the Journal of the American Medical Association said that before she became an editor, she got one phone call a month asking her to pose as the author of a ghost-written article. The article provides another bit of evidence that ghost-writing may be far more prevalent than most physicians and researchers realized. Yet, as Dr. DeAngelis said, ghost-writing is "manipulation by for-profits to alter what's in the (medical) literature so that they could sell their products."
Finally, the NY Times ran a story suggesting that pharmaceutical companies seem split about whether to submit information to online registries of controlled trials. These registries had been proposed as a way to prevent the companies from hiding unfavorable results of clinical trials.
Some companies, notably Eli Lilly, have apparently been quick to provide trial information to the registries. Dr. Alan Breier, the company's chief medical officer, said "fundamentally, what we're doing is in the interest of patients, and I think that this is the winning model, for academia, for industry, and the future."
On the other hand, some companies, e.g., Merck, Pfizer, and GlaxoSmithKline, have been stingy in the information they have provided to the NIH clinical trials registry, clinicaltrials.gov. Dr. Deborah Zarin, the director of the site, noted, for example, that Merck only said that one trial was a "one-year stury of an investigational drug in obese patients." Failing to provide crucial details, like the name of the drug, would make it impossible in the future to tell if Merck ever published a report of the trial's results.
The Times reported that "executives and press representatives at the companies said generally that disclosing too much information about early-state trials might reveal business or scientfic secrets." On the other hand, Dr. Breir of Lilly felt that it could supply information to the registry while still protecting its intellectual property.
In summary, physicians' efforts to make decisions for patients based on the best available research data are frustrated when companies hide or manipulate research results which put their products in a bad light. Manipulating or hiding research results betrays those patients who volunteered to participate in clinical trials intending to help advance science and improve patient care. Misleading advertising pushes patients to get treatments that are needlessly expensive, and sometimes needlessly hazardous. Too often, pharmaceutical companies seem to have forgotten their high-minded promises to help patients with better treatments in the pursuit of short-term profits.

Princess Health and Ghosts of Days Long Past. Princessiccia

Princess Health and Ghosts of Days Long Past. Princessiccia

ghost writing

Gusty 13:06 Add Comment

I have managed to track back the ghost-writing story to at least 1993.
In 1993, an editorial appeared in Lancet entitled "Ghost With a Chance in Publishing Undergrowth." (Anonymous. Ghost with a chance in publishing undergrowth. Lancet 1993; 342: 1498-99.) It clearly describes the ghost-writing phenomenon, "a typical sequence of events beigns with a publisher agreeing to prepare a review article for a drug company to 'raise awareness/profile' of a certain subject that is broadly related to the company's product. " Then, "a staff writer prepares the review to the sponsor's satisfaction, whereuponthe publishing house contacts a doctor with a special interest in the relevant topic to inquire whether he or she would like to be the guest author, subject to approval of the content, for an honorarium." The editorial noted, "negotiations between publishing house and guest author tend to be conducted over the telephone or in person. The final version, when submitted to the journal, may contain no clues about its origin. " Sounds familiar?
In 1994, an editorial in JAMA warned, "there are ghosts lurking in the bylines - shadowy figures who, increasingly, are in fact the actual writers (the authors, some old-fashioned folk would say) of what we editors receive." (Rennie D, Flanigin A. Authorship! authorship! guests, ghosts, grafters and the two-sided coin. JAMA 1994; 271: 469-470.)
A letter in response to the JAMA article briefly described a case very similar to the one Dr. Fugh-Berman described recently in the Journal of General Internal Medicine. (Kasper CK. Authorship! authorship! JAMA 1994; 271: 1904.) In reply, Rennie and Flanigin stated, "it should be obvious that this is both deceptive and disgraceful. The academic whose name appears on the printed paper, and on whose brow no laborious sweat has appeared, must surely know that the exchange of money takes place solely because the deception is seen by some company to be commercially worthwhile."
However, despite these earlier warnings, the practice of ghost-writing seems to have continued, and now involves not only editorials and reviews, but also reports of original research. The practice remains deceptive and disgraceful, and not only the physicians and scientists who serve as "guest authors," but also the shadowy legions of ghost-writers and their even more shadowy sponsors should be ashamed of it.

Princess Health and Ghosts of Days Long Past.Princessiccia

Princess Health and Ghosts of Days Long Past.Princessiccia

ghost writing

Gusty 13:06 Add Comment

I have managed to track back the ghost-writing story to at least 1993.
In 1993, an editorial appeared in Lancet entitled "Ghost With a Chance in Publishing Undergrowth." (Anonymous. Ghost with a chance in publishing undergrowth. Lancet 1993; 342: 1498-99.) It clearly describes the ghost-writing phenomenon, "a typical sequence of events beigns with a publisher agreeing to prepare a review article for a drug company to 'raise awareness/profile' of a certain subject that is broadly related to the company's product. " Then, "a staff writer prepares the review to the sponsor's satisfaction, whereuponthe publishing house contacts a doctor with a special interest in the relevant topic to inquire whether he or she would like to be the guest author, subject to approval of the content, for an honorarium." The editorial noted, "negotiations between publishing house and guest author tend to be conducted over the telephone or in person. The final version, when submitted to the journal, may contain no clues about its origin. " Sounds familiar?
In 1994, an editorial in JAMA warned, "there are ghosts lurking in the bylines - shadowy figures who, increasingly, are in fact the actual writers (the authors, some old-fashioned folk would say) of what we editors receive." (Rennie D, Flanigin A. Authorship! authorship! guests, ghosts, grafters and the two-sided coin. JAMA 1994; 271: 469-470.)
A letter in response to the JAMA article briefly described a case very similar to the one Dr. Fugh-Berman described recently in the Journal of General Internal Medicine. (Kasper CK. Authorship! authorship! JAMA 1994; 271: 1904.) In reply, Rennie and Flanigin stated, "it should be obvious that this is both deceptive and disgraceful. The academic whose name appears on the printed paper, and on whose brow no laborious sweat has appeared, must surely know that the exchange of money takes place solely because the deception is seen by some company to be commercially worthwhile."
However, despite these earlier warnings, the practice of ghost-writing seems to have continued, and now involves not only editorials and reviews, but also reports of original research. The practice remains deceptive and disgraceful, and not only the physicians and scientists who serve as "guest authors," but also the shadowy legions of ghost-writers and their even more shadowy sponsors should be ashamed of it.

Princess Health and Another Ghost Writing Update. Princessiccia

Princess Health and Another Ghost Writing Update. Princessiccia

ghost writing

Gusty 13:55 Add Comment

Another update on ghost writing...

First, I have put below something by Ted Harding about how to find the report from the UK House of Commons committee that looked into ghost writing.

---------------------
To find the materials from the Health Select Committee, locate the relevant items here.
These are under "Reports":* 5 April 2005 Fourth Report- The Influence of the Pharmaceutical Industry
There are two parts to the Report:
HC 42-I The main Report
HC 42-II Appendices including transcripts of Oral evidence
This Report covers a lot more than the issue of "ghostwriting",which can be located in the section "Use of journals" on pages53(para 195)-55(para 201) of the main report HC 42-I, with references to evidence. It is clear that the Comittee deplores it, but apparently does not recommend specific regulatory action.
In the Introduction to Part II (HC 42-II), section "Promotion of Medicines to Professionals" (paras 4.14-4.22) there is reference to controls on what pharmaceutical companies may do in this area. Mostly this refers to sponsorship of meetings and people, andthe like, and does not explicitly refer to anything related to "ghostwriting". These controls come under Medicines (Advertising) Regulations1994 (regulation 21--inducements and hospitality), breach of which is a criminal offence. There is also reference to The MHRA Guidelines on Promotion and Advertising, which I have not consulted to see what they say about "ghostwriting."
Further evidence, some not printed in the Report, can be found here. Of these items, the "Supplementary memorandum by AstraZeneca(PI 33A)" (a follow-on to the PI 33 in the Report Pt II) has a section "Role of Professional Medical Writers" which sets out their asserted atttitude to "ghostwriting".
Under "Uncorrected Oral Evidence" see:
* 25 November 2004 The Influence of the Pharmaceutical Industry
* 2 December 2004 The Influence of the Pharmaceutical Industry
* 16 December 2004 The Influence of the Pharmaceutical Industry
* 13 January 2005 The Influence of the Pharmaceutical Industry
* 20 January 2005 The Influence of the Pharmaceutical Industry
* 7 February 2005 The Influence of the Pharmaceutical Industry
As can be seen from HC 42-I and HC 42-II, oral Evidence was infact taken from Thu 9 Sept 2004 onwards, but only the "raw" evidence from the 2004-5 session (7 Feb 2005 on) is available; there seems to be none on the 2003-4 website.
---------------------

Second, I found a 1997 report of an attempt to get a ghost written review article published, quite similar to that described by Dr. Fugh-Berman in the Journal of General Internal Medicine. The 1997 incident was documented in the journal Anesthesiology (Cullen DJ. Ghostwriting in scientific anesthesia journals. Anesthesiology 1997; 87: 195-196.) It can be found on the web by starting here.
In fact, the 1997 article includes earlier references (which I am trying to track down) which include yet another incident similar to the 1997 and current cases, but this time from 1993.

So, in summary, it seems that ghost writing is not a new problem, just one that has lurked below the radar for quite a while. This makes it all the more important to address it. Until we do, it will have a corrosive effect on our trust in the medical scientific literature.

Princess Health and Another Ghost Writing Update.Princessiccia

Princess Health and Another Ghost Writing Update.Princessiccia

ghost writing

Gusty 13:55 Add Comment

Another update on ghost writing...

First, I have put below something by Ted Harding about how to find the report from the UK House of Commons committee that looked into ghost writing.

---------------------
To find the materials from the Health Select Committee, locate the relevant items here.
These are under "Reports":* 5 April 2005 Fourth Report- The Influence of the Pharmaceutical Industry
There are two parts to the Report:
HC 42-I The main Report
HC 42-II Appendices including transcripts of Oral evidence
This Report covers a lot more than the issue of "ghostwriting",which can be located in the section "Use of journals" on pages53(para 195)-55(para 201) of the main report HC 42-I, with references to evidence. It is clear that the Comittee deplores it, but apparently does not recommend specific regulatory action.
In the Introduction to Part II (HC 42-II), section "Promotion of Medicines to Professionals" (paras 4.14-4.22) there is reference to controls on what pharmaceutical companies may do in this area. Mostly this refers to sponsorship of meetings and people, andthe like, and does not explicitly refer to anything related to "ghostwriting". These controls come under Medicines (Advertising) Regulations1994 (regulation 21--inducements and hospitality), breach of which is a criminal offence. There is also reference to The MHRA Guidelines on Promotion and Advertising, which I have not consulted to see what they say about "ghostwriting."
Further evidence, some not printed in the Report, can be found here. Of these items, the "Supplementary memorandum by AstraZeneca(PI 33A)" (a follow-on to the PI 33 in the Report Pt II) has a section "Role of Professional Medical Writers" which sets out their asserted atttitude to "ghostwriting".
Under "Uncorrected Oral Evidence" see:
* 25 November 2004 The Influence of the Pharmaceutical Industry
* 2 December 2004 The Influence of the Pharmaceutical Industry
* 16 December 2004 The Influence of the Pharmaceutical Industry
* 13 January 2005 The Influence of the Pharmaceutical Industry
* 20 January 2005 The Influence of the Pharmaceutical Industry
* 7 February 2005 The Influence of the Pharmaceutical Industry
As can be seen from HC 42-I and HC 42-II, oral Evidence was infact taken from Thu 9 Sept 2004 onwards, but only the "raw" evidence from the 2004-5 session (7 Feb 2005 on) is available; there seems to be none on the 2003-4 website.
---------------------

Second, I found a 1997 report of an attempt to get a ghost written review article published, quite similar to that described by Dr. Fugh-Berman in the Journal of General Internal Medicine. The 1997 incident was documented in the journal Anesthesiology (Cullen DJ. Ghostwriting in scientific anesthesia journals. Anesthesiology 1997; 87: 195-196.) It can be found on the web by starting here.
In fact, the 1997 article includes earlier references (which I am trying to track down) which include yet another incident similar to the 1997 and current cases, but this time from 1993.

So, in summary, it seems that ghost writing is not a new problem, just one that has lurked below the radar for quite a while. This makes it all the more important to address it. Until we do, it will have a corrosive effect on our trust in the medical scientific literature.

Princess Health and Ghosts Busted: Another Update. Princessiccia

Princess Health and Ghosts Busted: Another Update. Princessiccia

ghost writing

Gusty 18:19 Add Comment

New World Association of Medical Editors Policy
The World Association of Medical Editors issued a new policy statement on ghostwriting. Its introduction states "The integrity of the published record of scientific research depends not only on the validity of the science but also on honesty in authorship." Furthermore, "The scientific record is distorted if the primary purpose of an article is to persuade readers in favor of a special interest, rather than to inform and educate, and this purpose is concealed." Thus, "WAME considers ghost authorship dishonest and unacceptable."
The policy declares that "Submitting authors bear primary responsibility for naming all contributors to manuscripts and describing their contributions." However, "Other parties, including companies�such as marketing, communications, and medical education companies who are paid to assist pharmaceutical and medical device companies in disseminating favorable messages about their products�may initiate the sequence of events for which the author is the final and most easily identified participant. These other participants are also responsible for ghost written manuscripts and addressing their roles should be part of the solution."
The policy includes the following possible sanctions for violations:
"1. publish a notice that a manuscript has been ghost written, along with the names of the responsible companies and the submitting author;
2. alert the authors' academic institutions, identifying the commercial companies;
3. provide specific names if contacted by the popular media or government organizations; and
4. share their experiences on the WAME Listserve and within other forums."
It all makes sense to me, but I wonder if any of the proposed sanctions are likely to have a powerful effect on the large health care organizations that sponsor the ghostwriting, nor the "medical education companies" that actually produce it.
Annals of Internal Medicine Announcement
Meanwhile, the Annals of Internal Medicine just put an announcement on its web-site that the journal editors are investigating the report of the ADVANTAGE trial, and "The editors will try to verify the number of cardiac events reported in The New York Times article. We will print a correction if we confirm that Lisse and colleagues reported patient outcomes incorrectly. " Sounds like a good idea, but this doesn't directly address the issue that the Times alleged that this trial was ghostwritten, and alleged that the true authorship of the trial was concealed from the journal editors and their readers. Let's see if there is more to come on this.
The Canadian Broadcasting Corporation Report on Ghostwriting
I found a fairly scary report that the CBC put out in 2003, which I wish I had seen then. It included an interview with a ghostwriter, one of three, in Vancouver, Montreal and Ottawa, that the reporters found. The anonymous ghostwriter declared:

• "I'm given an outline about what to talk about, what studies to site. [sic] They want us to be talking about the stuff that makes the drug look good. There's no discussion of certain adverse events. That's just not brought up."
• "You're being told [by the drug company] what to do. And if you don't do it, you've lost the job."
• "I expect that all the drug companies are doing it with all the drugs."
• "As long as I do my job well, it's not up to me to decide how the drug is positioned. I'm just following the information I'm being given."
• "The way I look at it, if doctors that have their name on it, that's their responsibility, not mine."

Spooky. Read it --and weep if what their anonymous interviewee said was even an approximation of the truth.

Princess Health and Ghosts Busted: Another Update.Princessiccia

Princess Health and Ghosts Busted: Another Update.Princessiccia

ghost writing

Gusty 18:19 Add Comment

New World Association of Medical Editors Policy
The World Association of Medical Editors issued a new policy statement on ghostwriting. Its introduction states "The integrity of the published record of scientific research depends not only on the validity of the science but also on honesty in authorship." Furthermore, "The scientific record is distorted if the primary purpose of an article is to persuade readers in favor of a special interest, rather than to inform and educate, and this purpose is concealed." Thus, "WAME considers ghost authorship dishonest and unacceptable."
The policy declares that "Submitting authors bear primary responsibility for naming all contributors to manuscripts and describing their contributions." However, "Other parties, including companies�such as marketing, communications, and medical education companies who are paid to assist pharmaceutical and medical device companies in disseminating favorable messages about their products�may initiate the sequence of events for which the author is the final and most easily identified participant. These other participants are also responsible for ghost written manuscripts and addressing their roles should be part of the solution."
The policy includes the following possible sanctions for violations:
"1. publish a notice that a manuscript has been ghost written, along with the names of the responsible companies and the submitting author;
2. alert the authors' academic institutions, identifying the commercial companies;
3. provide specific names if contacted by the popular media or government organizations; and
4. share their experiences on the WAME Listserve and within other forums."
It all makes sense to me, but I wonder if any of the proposed sanctions are likely to have a powerful effect on the large health care organizations that sponsor the ghostwriting, nor the "medical education companies" that actually produce it.
Annals of Internal Medicine Announcement
Meanwhile, the Annals of Internal Medicine just put an announcement on its web-site that the journal editors are investigating the report of the ADVANTAGE trial, and "The editors will try to verify the number of cardiac events reported in The New York Times article. We will print a correction if we confirm that Lisse and colleagues reported patient outcomes incorrectly. " Sounds like a good idea, but this doesn't directly address the issue that the Times alleged that this trial was ghostwritten, and alleged that the true authorship of the trial was concealed from the journal editors and their readers. Let's see if there is more to come on this.
The Canadian Broadcasting Corporation Report on Ghostwriting
I found a fairly scary report that the CBC put out in 2003, which I wish I had seen then. It included an interview with a ghostwriter, one of three, in Vancouver, Montreal and Ottawa, that the reporters found. The anonymous ghostwriter declared:

• "I'm given an outline about what to talk about, what studies to site. [sic] They want us to be talking about the stuff that makes the drug look good. There's no discussion of certain adverse events. That's just not brought up."
• "You're being told [by the drug company] what to do. And if you don't do it, you've lost the job."
• "I expect that all the drug companies are doing it with all the drugs."
• "As long as I do my job well, it's not up to me to decide how the drug is positioned. I'm just following the information I'm being given."
• "The way I look at it, if doctors that have their name on it, that's their responsibility, not mine."

Spooky. Read it --and weep if what their anonymous interviewee said was even an approximation of the truth.

Princess Health and Ghosts Busted: Some Additional Sources. Princessiccia

Princess Health and Ghosts Busted: Some Additional Sources. Princessiccia

AstraZeneca ghost writing

Gusty 12:21 Add Comment

Here is some additional background on the Journal of General Internal Mediciine / RcComms
/AstraZeneca ghost writing story.
The World Association of Medical Editors (WAME) List Server Discussion
The story first appeared in cyberspace as an edited transcript of a WAME list server discussion
that took place in January, 2005. For those interested, it makes for worthwhile reading. And it turns out that none of the points I made on Health Care Renewal this week were very original.
The Pharma Watch Report
The WAME discussion was picked up on the Pharma Watch blog out of Australia, (in a post entitled "Bleeding Misleading") and here things got interesting. A single comment was posted to this blog. The comment pointed out that the story seemed to contradict testimony of Dr. John Patterson, the Executive Vice President for Product Strategy, Licensing, and Business Development for AstraZeneca [UK] given to the UK House of Commons denying that the company had ever had articles ghostwritten, and also included a somewhat rude remark about that Dr. Patterson.
Pharma Watch's blogger, Michael Lascelles, then received a message from an AstraZeneca official asking him to remove these "potentially defamatory" remarks made in the comment. Lescelles removed the potentially offensive parts of the comment, but later noted (in a post entitled "I'm Going to be Sued Over This, But What the Heck,") that the story as told in the JGIM article suggested that "Dr John Patterson's comments to the House of Commons committee [were] inaccurate, to say the least."
The Portland Tribune Article
Finally, there was a news article in the Portland Tribune about the case, including an interview
with Dr. Martha Gerrity, one of the two co-editors of JGIM. In it she stated "the intent was to
bias the medical literature in favor of a pharmaceutical company's product.... This isn't
telling the truthful story about warfarin."
The Tribune article also included details about Rx Communications' and AstraZeneca's responses to the allegations made about them. The Tribune article stated that Rx Communications said that "there were actually two papers on warfarin in development, and the paper submitted to JGIM was indeed the work of the named author. According to their explanation, portions of the article Fugh-Berman was later asked to review were mistakenly sent to her when she was solicited to write a different article." Furthermore, AstraZeneca's public relations director, Julia Walker, said "the named author provided significant contributions over many months to the content and focus of the article." But Dr. Fugh-Berman called these explanations "ridiculous," given that "the article she was asked to write came to her not as an outline but as a completed 2,850-word manuscript, including 65 references and a title page with her name already on it."
The best way to conclude would be to again quote the JGIM editorial by Dr. Gerrity and Dr. William Tierney, " ghostwriting as apparently occured in this case "injects bias and untruth into the scientific dialogue in order to enhance corporate profits."

Princess Health and Ghosts Busted: Some Additional Sources.Princessiccia

Princess Health and Ghosts Busted: Some Additional Sources.Princessiccia

AstraZeneca ghost writing

Gusty 12:21 Add Comment

Here is some additional background on the Journal of General Internal Mediciine / RcComms
/AstraZeneca ghost writing story.
The World Association of Medical Editors (WAME) List Server Discussion
The story first appeared in cyberspace as an edited transcript of a WAME list server discussion
that took place in January, 2005. For those interested, it makes for worthwhile reading. And it turns out that none of the points I made on Health Care Renewal this week were very original.
The Pharma Watch Report
The WAME discussion was picked up on the Pharma Watch blog out of Australia, (in a post entitled "Bleeding Misleading") and here things got interesting. A single comment was posted to this blog. The comment pointed out that the story seemed to contradict testimony of Dr. John Patterson, the Executive Vice President for Product Strategy, Licensing, and Business Development for AstraZeneca [UK] given to the UK House of Commons denying that the company had ever had articles ghostwritten, and also included a somewhat rude remark about that Dr. Patterson.
Pharma Watch's blogger, Michael Lascelles, then received a message from an AstraZeneca official asking him to remove these "potentially defamatory" remarks made in the comment. Lescelles removed the potentially offensive parts of the comment, but later noted (in a post entitled "I'm Going to be Sued Over This, But What the Heck,") that the story as told in the JGIM article suggested that "Dr John Patterson's comments to the House of Commons committee [were] inaccurate, to say the least."
The Portland Tribune Article
Finally, there was a news article in the Portland Tribune about the case, including an interview
with Dr. Martha Gerrity, one of the two co-editors of JGIM. In it she stated "the intent was to
bias the medical literature in favor of a pharmaceutical company's product.... This isn't
telling the truthful story about warfarin."
The Tribune article also included details about Rx Communications' and AstraZeneca's responses to the allegations made about them. The Tribune article stated that Rx Communications said that "there were actually two papers on warfarin in development, and the paper submitted to JGIM was indeed the work of the named author. According to their explanation, portions of the article Fugh-Berman was later asked to review were mistakenly sent to her when she was solicited to write a different article." Furthermore, AstraZeneca's public relations director, Julia Walker, said "the named author provided significant contributions over many months to the content and focus of the article." But Dr. Fugh-Berman called these explanations "ridiculous," given that "the article she was asked to write came to her not as an outline but as a completed 2,850-word manuscript, including 65 references and a title page with her name already on it."
The best way to conclude would be to again quote the JGIM editorial by Dr. Gerrity and Dr. William Tierney, " ghostwriting as apparently occured in this case "injects bias and untruth into the scientific dialogue in order to enhance corporate profits."

Princess Health and More evidence of ghostwriting. Princessiccia

Princess Health and More evidence of ghostwriting. Princessiccia

ghost writing Merck Vioxx

Gusty 06:58 Add Comment

Yet more on ghost writing of scientific papers as posted here and here:

Quoting a New York Times article, Evidence in Vioxx Suits Shows Intervention by Merck Officials, April 24, 2005:

The Advantage trial [of VIOXX] was completed in 2000, but its results were not published until 2003, when they appeared in the Annals of Internal Medicine, a well-regarded journal. Dr. Jeffrey R. Lisse, a rheumatologist at the University of Arizona who is listed as the study's first author, said in an interview that at least two other journals had rejected the study because its results were not novel.

In the published study, Dr. Lisse reported that five patients taking Vioxx had suffered heart attacks during the trial, compared with one taking naproxen, a difference that did not reach statistical significance. But the paper never mentioned the three additional cardiac deaths of patients taking Vioxx, including the 73-year-old woman.

Dr. Lisse said that while he was listed as the paper's first author, Merck actually wrote the report, an unusual practice. "Merck designed the trial, paid for the trial, ran the trial," Dr. Lisse said. "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."
Dr. Lisse said he had never heard of the case of the woman who died, until told of it by a reporter. "Basically, I went with the cardiovascular data that was presented to me," he said.

Just how "unusual" is this practice of ghost-writing in the pharmaceutical industry?

-- SS

Princess Health and More evidence of ghostwriting.Princessiccia

Princess Health and More evidence of ghostwriting.Princessiccia

ghost writing Merck Vioxx

Gusty 06:58 Add Comment

Yet more on ghost writing of scientific papers as posted here and here:

Quoting a New York Times article, Evidence in Vioxx Suits Shows Intervention by Merck Officials, April 24, 2005:

The Advantage trial [of VIOXX] was completed in 2000, but its results were not published until 2003, when they appeared in the Annals of Internal Medicine, a well-regarded journal. Dr. Jeffrey R. Lisse, a rheumatologist at the University of Arizona who is listed as the study's first author, said in an interview that at least two other journals had rejected the study because its results were not novel.

In the published study, Dr. Lisse reported that five patients taking Vioxx had suffered heart attacks during the trial, compared with one taking naproxen, a difference that did not reach statistical significance. But the paper never mentioned the three additional cardiac deaths of patients taking Vioxx, including the 73-year-old woman.

Dr. Lisse said that while he was listed as the paper's first author, Merck actually wrote the report, an unusual practice. "Merck designed the trial, paid for the trial, ran the trial," Dr. Lisse said. "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."
Dr. Lisse said he had never heard of the case of the woman who died, until told of it by a reporter. "Basically, I went with the cardiovascular data that was presented to me," he said.

Just how "unusual" is this practice of ghost-writing in the pharmaceutical industry?

-- SS

Princess Health and Additional ghostbusting thoughts. Princessiccia

Princess Health and Additional ghostbusting thoughts. Princessiccia

ghost writing

Gusty 08:18 Add Comment

The revelation about "ghost writing" and false accreditation in the Journal of General Internal Medicine , a practice apparently for such purposes as "paving the road" for new drugs, was quite concerning to me as a former pharma professional. It also raises several critical questions:

1) Who are the personnel responsible for a program of foisting prewritten papers on to clinicians/scientists for them to "edit" and then claim first-authorship, a tactic that I would view as academic fraud?

2) What were the roles of non-clinical MBA's and marketing execs in such programs and decision making? Creating and implementing projects like this would require a lot of planning and discussion within "business process-centric", hierarchical pharmaceutical companies in my experience. Do such people know the effects such activities could have on science and the public's trust in scientific research? Do they care?

3) What impact does this type of activity have on EBM (Evidence-Based Medicine)? Sue Pelletier of Capsules astutely observes that "... this whole situation really is unbelievable, isn't it? Or at least, it should be. It makes me question the value of evidence-based medicine, if the evidence it is based upon is based on "studies" like this one." I agree.

4) What is the true size of this scandal? How many other potentially misleading, inaccurate or faulty "ghost papers" misaccredited to primary authors are present in the recent medical literature as a result of such initiatives, and could pharmas and other corporate entities be made to reveal this, e.g., under the U.S. Racketeer Influenced and Corrupt Organizations (RICO) Act or other U.S. or non-U.S. laws and statutes?

On October 15, 1970, the Organized Crime Control Act of 1970 became law. Title IX of the Act is the Racketeer Influenced and Corrupt Organizations Statute (18 U.S.C. �� 1961-1968), commonly referred to as the "RICO" statute. The purpose of the RICO statute is "the elimination of the infiltration of organized crime and racketeering into legitimate organizations operating in interstate commerce." S.Rep. No. 617, 91st Cong., 1st Sess. 76 (1969). However, the statute is sufficiently broad to encompass illegal activities relating to any enterprise affecting interstate or foreign commerce.

In addition, as I wrote at "US senator says FDA needs independent safety office" , insights into process flaws, inadequate leadership skillsets, and perhaps even corruption in high-stakes industries can be gleaned by who they won't hire. Perhaps it's not a coincidence that after my layoff from pharma and more than year-long search for a new position (which is back in academic medical informatics), I could not even secure interviews with several "Medical Education Companies."

It's bad enough that the ghostwriting practice occurs, but it's even worse that the papers themselves may not even be of decent quality. I was also disappointed but not surprised to read in the Journal of General Internal Medicine editorial "Scientific Discourse, Corporate Ghostwriting, Journal Policy, and Public Trust" that the article in question on anticoagulants, according to Dr. Adriane Fugh-Berman, was of low quality:

[This manuscript] consists of collated case reports with little to no assessment of case report quality. It is transparently biased. Controlled trials assessing interactions are only mentioned spottily; the writers seem unaware of many more trials that exist. When trials are mentioned, it is dismissively, as if the case reports showcased were just as credible. The fish oil section is particularly egregious. There is only a single case report that I know of that reports a possible interaction. Two clinical studies specifically designed to test fish oil with warfarin show no interaction, and long-term studies of fish oil show no effect on bleeding parameters. PC-SPES didn't interact with warfarin. It was ADULTERATED with warfarin. I could go on with other errors and misleading statements .

As a medical informaticist and the former director of Merck's scientific research libraries where we prided ourselves on the proven ability to perform comprehensive searches of the world's scientific literature (even the very obscure) for our scientists, I likely would not have missed existing clinical trials in the literature. Exactly what kind of people, and with what credentials, are the MEC's hiring?

Finally, it didn't take a genius to find the name of the company and drug even though no names were used in the JGIM article. The following google searches based on phrases from the article are very revealing: A search on anticoagulant+orthopedic+surgery+france shows "Exanta" as the third hit and the linked article indicates A-Z as the maker; a search on exanta+fda+hepatotoxicity pretty much confirms this drug as the one mentioned in the articles.

Much like in recent politics, the "World Library Computer" formed by the Internet and its search engines makes concealing certain business activities much harder than in the past.

Addendum: In the Guardian article "Not in my name" it is written that AstraZenica said:

Most pharmaceutical companies, including AstraZeneca, use professional writers to assist in manuscript development, when the named authors lack the time or expertise to produce a well-written publication."

I thought having the expertise to produce well-written, primary-author publications was a major criteria for academic credibility, recognition and advancement. However, we seem to now be discovering that like many other corporate functions, it's simply viewed as a skillset to be outsourced to increase profit.

Incredible.

-- SS

Princess Health and Additional ghostbusting thoughts.Princessiccia

Princess Health and Additional ghostbusting thoughts.Princessiccia

ghost writing

Gusty 08:18 Add Comment

The revelation about "ghost writing" and false accreditation in the Journal of General Internal Medicine , a practice apparently for such purposes as "paving the road" for new drugs, was quite concerning to me as a former pharma professional. It also raises several critical questions:

1) Who are the personnel responsible for a program of foisting prewritten papers on to clinicians/scientists for them to "edit" and then claim first-authorship, a tactic that I would view as academic fraud?

2) What were the roles of non-clinical MBA's and marketing execs in such programs and decision making? Creating and implementing projects like this would require a lot of planning and discussion within "business process-centric", hierarchical pharmaceutical companies in my experience. Do such people know the effects such activities could have on science and the public's trust in scientific research? Do they care?

3) What impact does this type of activity have on EBM (Evidence-Based Medicine)? Sue Pelletier of Capsules astutely observes that "... this whole situation really is unbelievable, isn't it? Or at least, it should be. It makes me question the value of evidence-based medicine, if the evidence it is based upon is based on "studies" like this one." I agree.

4) What is the true size of this scandal? How many other potentially misleading, inaccurate or faulty "ghost papers" misaccredited to primary authors are present in the recent medical literature as a result of such initiatives, and could pharmas and other corporate entities be made to reveal this, e.g., under the U.S. Racketeer Influenced and Corrupt Organizations (RICO) Act or other U.S. or non-U.S. laws and statutes?

On October 15, 1970, the Organized Crime Control Act of 1970 became law. Title IX of the Act is the Racketeer Influenced and Corrupt Organizations Statute (18 U.S.C. �� 1961-1968), commonly referred to as the "RICO" statute. The purpose of the RICO statute is "the elimination of the infiltration of organized crime and racketeering into legitimate organizations operating in interstate commerce." S.Rep. No. 617, 91st Cong., 1st Sess. 76 (1969). However, the statute is sufficiently broad to encompass illegal activities relating to any enterprise affecting interstate or foreign commerce.

In addition, as I wrote at "US senator says FDA needs independent safety office" , insights into process flaws, inadequate leadership skillsets, and perhaps even corruption in high-stakes industries can be gleaned by who they won't hire. Perhaps it's not a coincidence that after my layoff from pharma and more than year-long search for a new position (which is back in academic medical informatics), I could not even secure interviews with several "Medical Education Companies."

It's bad enough that the ghostwriting practice occurs, but it's even worse that the papers themselves may not even be of decent quality. I was also disappointed but not surprised to read in the Journal of General Internal Medicine editorial "Scientific Discourse, Corporate Ghostwriting, Journal Policy, and Public Trust" that the article in question on anticoagulants, according to Dr. Adriane Fugh-Berman, was of low quality:

[This manuscript] consists of collated case reports with little to no assessment of case report quality. It is transparently biased. Controlled trials assessing interactions are only mentioned spottily; the writers seem unaware of many more trials that exist. When trials are mentioned, it is dismissively, as if the case reports showcased were just as credible. The fish oil section is particularly egregious. There is only a single case report that I know of that reports a possible interaction. Two clinical studies specifically designed to test fish oil with warfarin show no interaction, and long-term studies of fish oil show no effect on bleeding parameters. PC-SPES didn't interact with warfarin. It was ADULTERATED with warfarin. I could go on with other errors and misleading statements .

As a medical informaticist and the former director of Merck's scientific research libraries where we prided ourselves on the proven ability to perform comprehensive searches of the world's scientific literature (even the very obscure) for our scientists, I likely would not have missed existing clinical trials in the literature. Exactly what kind of people, and with what credentials, are the MEC's hiring?

Finally, it didn't take a genius to find the name of the company and drug even though no names were used in the JGIM article. The following google searches based on phrases from the article are very revealing: A search on anticoagulant+orthopedic+surgery+france shows "Exanta" as the third hit and the linked article indicates A-Z as the maker; a search on exanta+fda+hepatotoxicity pretty much confirms this drug as the one mentioned in the articles.

Much like in recent politics, the "World Library Computer" formed by the Internet and its search engines makes concealing certain business activities much harder than in the past.

Addendum: In the Guardian article "Not in my name" it is written that AstraZenica said:

Most pharmaceutical companies, including AstraZeneca, use professional writers to assist in manuscript development, when the named authors lack the time or expertise to produce a well-written publication."

I thought having the expertise to produce well-written, primary-author publications was a major criteria for academic credibility, recognition and advancement. However, we seem to now be discovering that like many other corporate functions, it's simply viewed as a skillset to be outsourced to increase profit.

Incredible.

-- SS

Princess Health and Ghosts Busted. Princessiccia

Princess Health and Ghosts Busted. Princessiccia

ghost writing

Gusty 08:43 Add Comment

The Journal of General Internal Medicine (JGIM) has released early a very important article about how pharmaceutical companies infiltrate the peer-reviewed medical literature and use it as a marketing tool.
The whistle-blowing article by Dr. Adriane Fugh-Berman recounts how the author was approached to serve as the front author on a manuscript already written by a "medical education company" on behalf of a pharmaceutical company. The manuscript purported to be a review of interactions between warfarin and herbal remedies. The manuscript was provided to Dr. Fugh-Berman in essentially complete form, with her name on the first page as first author. The pharmaceutical company that sponsored the writing of this manuscript had developed a new oral anti-coagulant, already approved for use in France, and with a New Drug Application pending before the US Food and Drug Administration (FDA). Presumably, the company expected that the new drug would compete with warfarin. Thus, the apparent goal of the manuscript was to disparage warfarin, the drug with which the pharmaceutical company's new product would compete.
Dr. Fugh-Berman rejected the offer from the medical education company. As luck would have it, however, the company recruited another front author, who submitted the manuscript to the Journal of General Internal Medicine, who in turn forwarded the article to Dr. Fugh-Berman as a peer-reviewer. When she recognized the manuscript for what it was, she notified the journal editors.
Prompted by this incident, Dr. Fugh-Berman began investigating the relationships among pharmaceutical and biotechnology companies and medical education companies. Based on this investigation, she made the following points:

• "Pharmaceutical companies routinely seed medical literature with revews or commentaries that advantageously frame a marketed drug, but some sponsored articles never mention the targeted drug."
• "Companies regularly fund articles and talks that never mention the targeted drug, but are meant to disadvantage the competition."
• "Articles are usually written by a medical education company (MEC) that receives funding from the pharmaceutical company."
• " Academic physicians are recruited to sign these articles. The division of labor for such acorporate-sponsored article is rarely equal: although the signed author is invited to make changes, the primary obligation of the academic coauthor is to claim authorship."
• "The primary author from the MEC remains anonymous, and any instructions given to the primary author regarding tone or emphasis are not shared with the named author."
• "True incidence of corporate ghost authorship is unknown: anecdotally, many of my colleagues who speak at national meetings have been approached with such offers."
• "The placement of articles in peer-reviewed journals is a valued marketing technique. For example, an industry conference, titled "Publication Planning 2003: Utilizing ScientificallyAccurate, Commercially Relevant Strategies for Optimal Drug Exposure" had a conference brochure that stated, "'For a manufacturer, having research published in a highly regarded peer review [sic] medical journal or presented at a leading conference is desirable.'" One workshop described changes in how pharmaceutical companies handle publishing so that "'These changes have seen publications shift from being an academic, data-driven pursuit to adopting a message-driven model that is part of a broader communication strategy and integral to pharmaceutical life-cycle management.'"

So, to summarize up to this point: Corporations, including but not necessarily only pharmaceutical corporations, may use the peer-reviewed medical literature as a marketing tool. To disguise their intent, they work through medical education companies, who ghost write articles in a "message-driven model," and then recruit academics to serve as front authors for them. The articles may be published without acknowledging who really wrote them, nor what their intent really was.
Dr. Fugh-Berman has done us the important service of describing a previously undisclosed kind of attack on the scientific basis of medical practice.
An accompanying editorial in JGIM called the events described by Dr. Fugh-Berman "an egregious case of unethical behavior by an author, a pharmaceutical manufacturer, and a medical education company." Furthermore, it charged "Publishing biased literature is not simply 'getting the message out' for the pharmaceutical client of the medical education company. It injects bias and untruth into the scientific dialogue in order to enhance corporate profits." "How much is sullying the medical literature worth in market share?"
The editorial noted that JGIM has changed its policy to require all real authors of articles to be acknowledged, and all financial arrangements among authors and other interested parties to be revealed. Apparently, the World Association of Medical Editors (WAME) will also be similarly changing their policy.
Dr. Fugh-Berman went further, suggesting developing a "publicly available, regularly updated database of conflicts of interest and ethical transgressions." "And we need a mechanism foracademicians to expose the more subtle strategies used by drug companies to affect prescribing."
In my humble opinion, the issues are even more global, and the strategies needed to combat thisegregious assault on the scientific basis of medical practice need to be broader as well.

• The scope of this practice, as Dr. Fugh-Berman noted, is unclear. We cannot assume that its use is restricted only to pharmaceutical companies. We have seen that mismanagement and unethical behavior occurs in a variety of health care organizations. It is therefore quite possible that organizations other than pharmaceutical companies use stealth techniques to inject marketing and propaganda into the scientific literature.
• Although revising journal policies is a worthwhile first step, it is doubtful that asking authors who have already agreed to front for ghost authors to tell the truth will have much effect.
• Dr. Fugh-Berman's call for a database of conflicts of interest and ethical transgressions and to facilitate whistle-blowing about them are excellent ideas. One could view Health Care Renewal as a crude first attempt to develop such a database and such a mechanism.
• We need to develop watch-dog organizations within health care to cope with what now seems an epidemic of mismanagement, conflicts of interests, dishonesty, unethical behavior, and outright crime and corruption. Main-line medical organizations have so far been reluctant to step into this fray, but maybe they can be persuaded. If not, we need to develop new organizations to fight external attacks on medical professsionalism.

Note: thanks to Revere for first publicizing the JGIM article on Effect Measure. His comments are here.
Addendum: Dr. Fugh-Berman today also published a commentary in the Manchester Guardian on this case. In it, she names names, which she did not do in her JGIM article. The medical education was the British RxComms. On its web-site is the statement that RxComms writes "everything from abstracts to full manuscripts; from clinical trial reports to sales aids and slide kits." The pharmaceutical company was AstraZeneca, and the drug they hoped would compete with warfarin was ximelagatran. Dr. Fugh-Berman noted that RxComms claimed that the manuscript sent to her was actually written by the person named as first author in the version sent to JGIM. AstraZeneca claimed that it follows strict guidelines that require authors to take responsbility of the content of the articles they write. Nonetheless, "Most pharmaceutical companies, including AstraZeneca, use professional writers to assist in manuscript development, when the named authors lack the time or expertise to produce a well-written publication."

Princess Health and Ghosts Busted.Princessiccia

Princess Health and Ghosts Busted.Princessiccia

ghost writing

Gusty 08:43 Add Comment

The Journal of General Internal Medicine (JGIM) has released early a very important article about how pharmaceutical companies infiltrate the peer-reviewed medical literature and use it as a marketing tool.
The whistle-blowing article by Dr. Adriane Fugh-Berman recounts how the author was approached to serve as the front author on a manuscript already written by a "medical education company" on behalf of a pharmaceutical company. The manuscript purported to be a review of interactions between warfarin and herbal remedies. The manuscript was provided to Dr. Fugh-Berman in essentially complete form, with her name on the first page as first author. The pharmaceutical company that sponsored the writing of this manuscript had developed a new oral anti-coagulant, already approved for use in France, and with a New Drug Application pending before the US Food and Drug Administration (FDA). Presumably, the company expected that the new drug would compete with warfarin. Thus, the apparent goal of the manuscript was to disparage warfarin, the drug with which the pharmaceutical company's new product would compete.
Dr. Fugh-Berman rejected the offer from the medical education company. As luck would have it, however, the company recruited another front author, who submitted the manuscript to the Journal of General Internal Medicine, who in turn forwarded the article to Dr. Fugh-Berman as a peer-reviewer. When she recognized the manuscript for what it was, she notified the journal editors.
Prompted by this incident, Dr. Fugh-Berman began investigating the relationships among pharmaceutical and biotechnology companies and medical education companies. Based on this investigation, she made the following points:

• "Pharmaceutical companies routinely seed medical literature with revews or commentaries that advantageously frame a marketed drug, but some sponsored articles never mention the targeted drug."
• "Companies regularly fund articles and talks that never mention the targeted drug, but are meant to disadvantage the competition."
• "Articles are usually written by a medical education company (MEC) that receives funding from the pharmaceutical company."
• " Academic physicians are recruited to sign these articles. The division of labor for such acorporate-sponsored article is rarely equal: although the signed author is invited to make changes, the primary obligation of the academic coauthor is to claim authorship."
• "The primary author from the MEC remains anonymous, and any instructions given to the primary author regarding tone or emphasis are not shared with the named author."
• "True incidence of corporate ghost authorship is unknown: anecdotally, many of my colleagues who speak at national meetings have been approached with such offers."
• "The placement of articles in peer-reviewed journals is a valued marketing technique. For example, an industry conference, titled "Publication Planning 2003: Utilizing ScientificallyAccurate, Commercially Relevant Strategies for Optimal Drug Exposure" had a conference brochure that stated, "'For a manufacturer, having research published in a highly regarded peer review [sic] medical journal or presented at a leading conference is desirable.'" One workshop described changes in how pharmaceutical companies handle publishing so that "'These changes have seen publications shift from being an academic, data-driven pursuit to adopting a message-driven model that is part of a broader communication strategy and integral to pharmaceutical life-cycle management.'"

So, to summarize up to this point: Corporations, including but not necessarily only pharmaceutical corporations, may use the peer-reviewed medical literature as a marketing tool. To disguise their intent, they work through medical education companies, who ghost write articles in a "message-driven model," and then recruit academics to serve as front authors for them. The articles may be published without acknowledging who really wrote them, nor what their intent really was.
Dr. Fugh-Berman has done us the important service of describing a previously undisclosed kind of attack on the scientific basis of medical practice.
An accompanying editorial in JGIM called the events described by Dr. Fugh-Berman "an egregious case of unethical behavior by an author, a pharmaceutical manufacturer, and a medical education company." Furthermore, it charged "Publishing biased literature is not simply 'getting the message out' for the pharmaceutical client of the medical education company. It injects bias and untruth into the scientific dialogue in order to enhance corporate profits." "How much is sullying the medical literature worth in market share?"
The editorial noted that JGIM has changed its policy to require all real authors of articles to be acknowledged, and all financial arrangements among authors and other interested parties to be revealed. Apparently, the World Association of Medical Editors (WAME) will also be similarly changing their policy.
Dr. Fugh-Berman went further, suggesting developing a "publicly available, regularly updated database of conflicts of interest and ethical transgressions." "And we need a mechanism foracademicians to expose the more subtle strategies used by drug companies to affect prescribing."
In my humble opinion, the issues are even more global, and the strategies needed to combat thisegregious assault on the scientific basis of medical practice need to be broader as well.

• The scope of this practice, as Dr. Fugh-Berman noted, is unclear. We cannot assume that its use is restricted only to pharmaceutical companies. We have seen that mismanagement and unethical behavior occurs in a variety of health care organizations. It is therefore quite possible that organizations other than pharmaceutical companies use stealth techniques to inject marketing and propaganda into the scientific literature.
• Although revising journal policies is a worthwhile first step, it is doubtful that asking authors who have already agreed to front for ghost authors to tell the truth will have much effect.
• Dr. Fugh-Berman's call for a database of conflicts of interest and ethical transgressions and to facilitate whistle-blowing about them are excellent ideas. One could view Health Care Renewal as a crude first attempt to develop such a database and such a mechanism.
• We need to develop watch-dog organizations within health care to cope with what now seems an epidemic of mismanagement, conflicts of interests, dishonesty, unethical behavior, and outright crime and corruption. Main-line medical organizations have so far been reluctant to step into this fray, but maybe they can be persuaded. If not, we need to develop new organizations to fight external attacks on medical professsionalism.

Note: thanks to Revere for first publicizing the JGIM article on Effect Measure. His comments are here.
Addendum: Dr. Fugh-Berman today also published a commentary in the Manchester Guardian on this case. In it, she names names, which she did not do in her JGIM article. The medical education was the British RxComms. On its web-site is the statement that RxComms writes "everything from abstracts to full manuscripts; from clinical trial reports to sales aids and slide kits." The pharmaceutical company was AstraZeneca, and the drug they hoped would compete with warfarin was ximelagatran. Dr. Fugh-Berman noted that RxComms claimed that the manuscript sent to her was actually written by the person named as first author in the version sent to JGIM. AstraZeneca claimed that it follows strict guidelines that require authors to take responsbility of the content of the articles they write. Nonetheless, "Most pharmaceutical companies, including AstraZeneca, use professional writers to assist in manuscript development, when the named authors lack the time or expertise to produce a well-written publication."