Questions raised about Avandia tests

Despite government investigations into the safety of diabetes drug Avandia, test subjects are still being recruited for studies into the controverial drug, according to a report.

That has some researchers scratching their heads, since regulators in Canada and the US are grappling with what to do about the drug.

"Exposing thousands of people to this drug for many years, just to see if existing studies are right, doesn't make a lot of sense," says Dr. David Juurlink, the scientist who was the lead investigator in the ICES study that compared Avandia and Actos.

"The idea that you would enroll tens of thousands of patients into a study and give them this drug for years just to see if it is really more dangerous, that to me that is something you might do to guinea pigs, not to patients," he says.

Prof. Jonathan Kimmelman, of the Biomedical Ethics Unit at McGill University in Montreal has reviewed the research so far and says he too is concerned.

"You are randomizing patients to a drug that has an unfavourable risk-benefit balance. That is not right," he said.

Three studies in as many years have raised concerns about the safety of the drug.

Avandia's potential to raise the risk of heart attacks in some patients was brought to light in a 2007 New England Medical Journal article that reported a 43 per cent higher risk of heart attacks among Avandia patients when compared with those taking other diabetes drugs, including Actos.

Then last June, scientists working on a large study called RECORD, concluded that Avandia did increase heart failure risk in some patients, but didn't increase the risk of cardiovascular death compared with standard diabetes drugs.

The pendulum swung again last August when a Canadian study published in the British Medical Journal concluded that Avandia carried a higher risk of heart failure and death than Actos.

Dr. Hertzel Gerstein of McMaster University in Hamilton and lead Canadian investigator of one study, defended the research. "The question we are asking on the trial is overall, are the benefits such that they outweigh the risks of the drug?" he said.

 

 

 

Peering over the edge into assisted suicide

In today's Toronto Star, I address the issue of assisted suicide -- and the argument that euthanasia is practiced so often in hospitals in all but name, that we should consider simply legalizing it.

Starving to death in a hospital bed is a horrible way to die, says an expert on the ethics of death, and it may be time to allow more overt ways of ending the lives of the terminally ill.

Wayne Sumner, a University of Toronto philosophy professor writing a book on assisted suicide, says while euthanasia is illegal in Canada, terminally ill patients or their families can refuse food, water and life-sustaining treatment.

"We tip-toe up to the barrier," says Wayne Sumner, who will speak about assisted suicide at UofT's Joint Centre for Bioethics on Wednesday afternoon.

"We peer over the edge, but seem reluctant to take that next step."

Sumner says there is no practical difference between letting someone starve to death, as is now done when feeding tubes are removed, and the more overt act of instructing a doctor to inject a lethal dose of medication to hasten death.

"If someone is refusing food and water, it's hard to see that the intention is anything but death," he says.

As such, he says, Canada should consider taking euthanasia out of the Criminal Code.

The peg for the story is a seminar to be given this afternoon by the University of Toronto's Joint Centre for Bioethics at their new home at 155 College St., Ste. 754, in Toronto. The centre often webcasts its seminars. Sumner will outline how he came to his conclusions, by addressing the agruments against allowing assisted suicide. Dr. Lawrence Librach of the Temmy Latner Centre for Palliative Care at Mount Sinai Hospital will provide commentary.

Moira McQueen, director of the Canadian Catholic Bioethics Institute, does not agree with Sumner that taking the next step to allow euthanasia would be the compassionate thing to do, as a way of alleviating suffering for both patients and family under the current system.

Every patient, she says,  has the right to refuse treatment or food, and let nature take its course.

"With euthanasia, you're not letting anything take its course," she says.

It is too big a leap to say that because people can refuse treatment or nourishment, they should actively take their own lives, she says.

"We all want to be compassionate, but we want to make sure we're doing the right thing, too."

A private member's bill by Bloc Quebecois MP Francine Lalonde to allow doctor-assisted suicide is currently before Parliament. Assisted suicide is allowed in three U.S. states – Oregon, Montana and Washington state – and in Belgium, Luxemburg, the Netherlands and Switzerland.

A Swiss clinic, Dignitas, has become a destination for people around the world seeking physician-assisted suicide, with more than 1,000 people travelling to Zurich since the clinic opened 12 years ago – including 10 from Canada. The Swiss government is now considering restricting suicides by foreigners, with Justice Minister Eveline Widmer-Schlumpf saying last October, "As a country, we aren't interested in attracting suicide tourism."

Sumner said the move could put political pressure on other governments to allow assisted suicide, since people will soon no longer have the option of flying out of the country for the procedure.

More on salami slicing -- Cymbalta ads ordered pulled

Today, I had a story in the Toronto Star about an issue I touched on in this blog last week: Salami slicing, or the re-use of clinical trial data in more than one journal study.

I spoke to Glen Spielmans, who wrote a study on the practice after looking into claims made in TV ads by Eli Lilly about its antidepressant Cymbalta.

As he went through every study he could find on Cymbalta – which is also known by its generic name, duloxetine – Spielmans began feeling as if he was reading the same study over and over again, sort of an academic déjà vu.

"There just aren't that many data to do all these secondary analyses on," Spielmans said in an interview. "That raised a flag for me."

I also spoke to a cancer researcher that while salami slicing does happen, it's worth remembering that trials are often designed so the data can be sliced up later.

"I would be careful of anything that's given a folksy name," says Dr. Ralph Meyer, director of the National Cancer Institute of Canada's Clinical Trials Group at Queen's University. ...

"Clinical trials are a lot of work. They're a lot of expense," he says.

Trials that Meyer has run, for instance, have looked at such standard questions as the safety and effectiveness of a new treatment but have also used the opportunity to examine the cost-effectiveness of the procedure or the treatment's impact on a patient's quality of life. 

Jocalyn Clark, a researcher at the University of Toronto and an editor at the journal PLoS Medicine, says top journals like hers require all authors to declare if any part of the underlying research has been – or soon will be – published elsewhere.

She said universities and hospitals need to tell their researchers that slami slicing is not acceptable, and that academics taking part in the practice risk ruining their reputations with the journals they count on to publish their studies. In a part of the stroy that had to be cut for length, she equated the practice to ghostwriting, in that academics slicing up their data are not being fully honest with readers.

Meanwhile, the Food and Drug Administration in the U.S. has sent a letter to Eli Lilly ordering to pull its "misleading" print ads for Cymbalta.

Promotional materials are misleading if they fail to reveal material facts in light of the representations made by the materials or with respect to consequences that may result from the use of the drug as recommended or suggested by the materials. The Print Ad is misleading because it presents various efficacy claims for Cymbalta, but fails to communicate any risk information in the main part of the ad.




 

Paxil costs Glaxo $1 billion or more: report

Settling lawsuits over its controversial anti-depressant Paxil has cost Glaxo SmithKline some $1-billion in court-ordered and out-of-court settlements, Bloomberg News reports.

“I don’t think this is within the boundaries of current assumptions for analysts.” Navid Malik, an analyst at Matrix Corporate Capital in London, is quoted as saying.

Another analyst, Savvas Neophytou, a Panmure Gordon analyst in London, says a $1.5 billion liability is possible.

The settlements result from suits in which people taking the drug caused them to contemplate suicide or birth defects in their children. In each of the cases, the plaintiffs allege that Glaxo knew of the dangers.

As part of the total, Glaxo, the U.K.’s largest drugmaker, so far has paid $200 million to settle Paxil addiction and birth-defect cases and $400 million to end antitrust, fraud and design claims, according to the people and court records.

The $1 billion “would be worse than many people are expecting,” said Navid Malik, an analyst at Matrix Corporate Capital in London. “I don’t think this is within the boundaries of current assumptions for analysts.”

The London-based company hasn’t disclosed the settlement total in company filings. It has made public some accords. Glaxo’s provision for legal and other non-tax disputes as of the end of 2008 was 1.9 billion pounds ($3.09 billion), according to its latest annual report. This included all legal matters, not just Paxil. The company said 112 million pounds of this sum would be “reimbursed by third-party issuers.”

The drugmaker has reduced its insurance coverage to contain costs, “accepting a greater degree of uninsured exposure,” the annual report states. “Recent insurance loss experience, including pharmaceutical product-liability exposures, has increased the cost of, and narrowed the coverage afforded by, insurance for pharmaceutical companies generally,” Glaxo said.

Glaxo declined to confirm the $1 billion figure. “Paxil has been on the market in the U.S. since 1993. Like many other pharmaceutical products, it has been the subject of different kinds of litigation over the years,” said Sarah Alspach, a spokeswoman for Glaxo, in an e-mailed statement. “It would be inappropriate and potentially misleading to aggregate payments in these various types of litigation.”

Chief Executive Officer Andrew Witty has moved to replace revenue lost to generic versions of drugs such as Paxil. Worldwide, Paxil generated about 514 million pounds in sales last year, or 2.1 percent of the total. Glaxo closed up 5 pence to 1,303 pence in London trading Dec. 11, down 8.8 percent from a year ago.

About 450 suicide-related Paxil cases were settled. Only about a dozen haven’t been, the people said. The $1 billion total doesn’t include more than 600 claims that Paxil caused birth defects.

A Philadelphia jury on Oct. 13 found the drugmaker should pay $2.5 million to the family of Lyam Kilker, a 3-year-old boy born with a heart defect after his mother took Paxil while pregnant. Based on that outcome, an analyst estimated the company may potentially face additional verdicts in birth-defect cases waiting to be tried in Pennsylvania.

“A liability totaling $1.5 billion is possible,” wrote Savvas Neophytou, a Panmure Gordon analyst in London, in a note to investors the day after the Kilker verdict. He still recommended buying Glaxo shares because a likely appeal may reduce the amount paid by the company.

 

Glaxo loses Paxil lawsuit, more details

I have blogged about this verdict already today, but new details are beginning to emerge.

The $2.5 million (US) award granted by a Philadelphia jury in a verdict handed down this morning against GlaxoSmithKline in a lawsuit over its anti-depressant Paxil is more than twice what the plaintiff was seeking.

Michelle David, suing on behalf of her son Lyam Kilker, who turns four next week, had sought $1.2 million to cover future medical costs and other damages. The settlement granted by the jury in a 10-2 vote matches that awarded five years ago when the drug giant agreed to pay the state of New York $2.5 million to resolve claims that it suppressed research showing that Paxil may increase suicide risk in young people.

David's lawyer, Sean Tracey, hailed the verdict afterward, saying it was the first to "get a jury saying the drug caused the injury."

Business analysts following the company, however, were not so sure.

“I don’t think the link is proven, so there will likely be collective settlements which will keep costs low,” Navid Malik, an analyst at Matrix Corporate Capital in London with a buy rating on the stock, said in an e-mail. “If this was a threat to GSK, the first verdict might have been 100 times greater.”

Glaxo American depositary receipts, each representing two ordinary shares, fell 5 cents to $39.73 at 1:07 p.m. in New York Stock Exchange composite trading, after dropping as much as 1.4 per cent when the verdict was announced. Glaxo fell 14 pence, or 1.1 per cent, to 1,246.5 pence in London.

I have yet to see the full decision by the jury, but Bloomberg is quoting it as saying that the jury found that Glaxo officials “negligently failed to warn” the doctor treating Lyam’s mother about Paxil’s risks and concluded the medicine was a “factual cause” of the child’s heart defects.

On the other hand, the jury also found that Glaxo’s handling of the drug wasn’t “outrageous,” meaning the family couldn’t seek punitive damages against the British drug company.

In a statement after the verdict came down the company said it disagreed with the decision and will appeal.

GlaxoSmithKline disagrees with the verdict and will appeal. While we sympathize with Lyam Kilker and his family, the scientific evidence does not establish that exposure to Paxil during pregnancy caused his condition. Very unfortunately, birth defects occur in three to five per cent of all live births, whether or not the mother was taking medication during pregnancy.

I have called Glaxo for more comment, but have not yet heard back.

Glaxo spokesman Kevin Colgan called and read me the statement quoted above.
 

 

 

'Serious danger' when doctors are paid by pharma

An editorial in the Boston Globe, which recently reported on 60 Massachusetts doctors who took $580,000 (US) in payments from drug companies over four years, calls for the practice to be banned outright.

The danger posed by this practice is serious: Research shows that getting money from the pharmaceutical industry can cloud doctors’ judgment when evaluating studies and side effects, as well as when they are prescribing medication. In addition, when reputed doctors rely on company material to promote a new drug to their colleagues, they also help broaden its use. Sometimes, the presentations end up encouraging the use of a drug for purposes beyond what it has been approved for by the Food and Drug Administration.

Massachusetts General Hospital, Brigham and Women’s Hospital, and McLean Hospital - all of which also employ doctors who have received money from Eli Lilly this year - will prohibit their doctors from receiving speakers’ fees from the pharmaceutical industry starting today. Other hospitals in Massachusetts and around the country should follow their lead immediately.

Efforts by Eli Lilly to set up an online registry of such payments are not enough, the editorial says. Merck plans to set up a similar registry in the coming months.

While transparency is a good first step that exposes doctors’ financial relationships to the broader medical community, it is unlikely to affect how patients view their doctors. More important, it will not address the subtle ways the payments influence and interfere with patient care.

Patients trust doctors as stewards of their health. They revere them as scientists who can exercise sound, independent judgment. Allowing doctors to promote drugs for pharmaceutical companies takes advantage of that trust and reverence. It also compromises doctors’ most important work: treating people who are ill.

The Lilly registry details $22 million (US) in payments to American doctors in just one fiscal quarter -- providing, it seems, a slice of just how big an issue this is.

Meanwhile, the University of Wisconsin, which has been rocked by revelations of the close ties of many of its researchers to medical device companies and ghostwriting, has backed off plans to ban its professors from collecting fees from the companies whose products they are supposed to be researching.

University of Wisconsin officials have watered down proposed conflict of interest rules, allowing orthopedic surgeons and other doctors who implant devices to earn large sums of money making presentations for medical device companies.

The new policy would keep in place a ban on UW doctors giving talks about medications for drug companies.

Not addressed in the policy is the university's own relationship with the drug industry, which has come under scrutiny in a series of stories this year by the Journal Sentinel.

The university receives several million dollars a year from drug-makers to sponsor doctor education activities, some of which have been criticized as promotional efforts to sell expensive brand name drugs.

But it is the exemption for the device-makers and the ban on drug-only talks that is riling up doctors at UW as part of a high stakes ethics battle simmering at medical schools across the country.

At issue is whether doctors should be free to hire themselves out as promotional speakers and consultants to drug and medical device makers and how much financial influence those firms should wield at academic medical centers.

"It's the subject of animated hallway conversations and nasty e-mails," said a UW doctor who asked not to be identified. "The fever pitch is high."

The university declined comment.

Ghostwriting: 'What's the harm?'

Ever since the Toronto Star broke the story of a McGill University professor's involvment with ghostwriters, there has been a growing debate across Canada about the practice.

In an unsigned editorial put online this morning, the Montreal Gazette asks, "What's the harm?" Afterall, it says, there's no evidence Sherwin intended to deceive anyone and the article in question was in line with the rest of her scholarship.

It's an important question. Across the country in Victoria, BC, the Time Colonist offers an answer:

Why is that important? First, DesignWrite is paid by pharmaceutical giant Wyeth to promote its drugs. But there was no mention of those co-authors in the article. That could mislead readers into believing the report was independent, when it was not.

Second, the article concluded that estrogen therapy helps prevent memory loss. But Wyeth is a producer of estrogen-based medications. In the research field, such an obvious conflict of interest could invalidate the findings, if it were known.

The danger, in other words, isn't just that bad science gets portrayed as good, but that good science gets dismissed as tainted. Both outcomes are dangerous to public health.

The Gazette seems to understand this, too, concluding its editorial with a discussion of the importance of the issue and a comparison to politicians -- who rarely write the speeches they give.

And this is different from writing speeches for politicians. The people who do that are usually partisans who share the views of their employer and who, in fact, might well be part of the team developing both policy and political strategy. In other words, both writer and reader share essentially the same goal.

That is very much not the case with a drug-company employee and a scientist. The aims they serve are quite different and often opposed. And maintaining that difference is often quite literally a matter of life and death. Sherwin's "error" suggests that at the very least, academics need to update and clarify the ethics that guide them.

McGill bioethicist Margaret Somerville joins in the debate, as well, in a column in the Gazzette. She questions whether we can judge researchers who used ghostwriters a decade (or less) ago based on the ethics of today, quoting British Lord Denning saying that "you can't look at 1956 events with 1964 glasses."

Just as the law evolves and science evolves, so too ethics evolves and something we now rightly regard as unethical might not have been so characterized in the past.

Much has changed in the last few years with respect to the ethics of academic publishing. Practices that were considered normal just a few years ago, such as placing on research articles the names of people who did not participate directly in the research (for instance, a principal investigator whose only connection with the research was that his research grant supported it) are now considered unethical.

She does not, however, make the case that using drug company paid ghostwriters was considered acceptable in 2000 when Sherwin's article appeared -- or in 1964, for that matter.

Meanwhile, the medical freelancers whose ranks make up the anonymous ghostwriters, have begun to speak up. One, Kate Johnson of Montreal, cautions in her blog about "throwing the baby out with the bathwater" by letting the ghostwriting scandal end the practice of researchers using editors to smooth out their prose.

As a medical editor, I help researchers with their writing - enabling them to communicate the results of their studies to the wider medical community.

This is not ghostwriting.

But in their haste to distance themselves from this ghostwriting exposé of the pharmaceutical industry, medical schools and academic journals may intimidate researchers from seeking the appropriate help of professional writers and editors.

In doing so they risk losing a great deal of valuable research done by brilliant investigators who can’t write.

No reporter would discount the role of a good editor. Any story that appears in a newspaper has been edited two or three or more times before it appears in print. Johnson is right, this is not ghostwriting.

Ghostwriting happens when an anonymous writer prepares an article that is edited by a respected researcher in the field. The editor's name then appears on the paper as author. 

No newspaper I know assigns bylines that way.

In a letter to the Boston Globe in response to an editorial about ghostwriting, medical freelancer Judith Pepin likewise sees nothing wrong with researchers getting help with their writing -- a skill she says many don't have.

I agree wholeheartedly that ghostwriting (undisclosed drafting of a manuscript) is a clear violation of ethics. However, acknowledged medical writing help is not ghostwriting.

In addition to assistance with writing, editing, and fact-finding, the medical writer lends valuable expertise to the lead author in the stylistic requirements of the many scientific journals to which manuscripts are submitted for publication.

This is a collaborative effort between the writer and the authors, and in no way, should be lumped in the category of “ghostwriting.’’

Also a good point. Editing is not the same as ghostwriting.

But it can still be wrong if the editor is getting money from the people whose products are being written about.

Collaboration is at the heart of good science. More people involved in the writing of a scientific article is can be a good thing, if it ensures that more facts and possiblities are brought to the table, discussed and presented to the reader. 

It only becomes an issue when some of those at the table have a possible conflict of interest, and it isn't diclosed.

Ghostwriting -- why they do it

A prominent hormone replacement therapy researcher exposed by the New York Times last December to have put his name on ghostwritten studies for estrogen drug company Wyeth Pharmaceuticals has broken his silence to say he's sorry.

Seattle blogger William Heisel, a former award-winning health reporter for the LA Times, managed to reach Australisn researcher John Eden by e-mail, where others had failed.

He was surprisingly forthcoming and said he regrets the decision.

"We academics are under some pressure to 'publish or perish,'" Eden wrote. "Performance evaluation of at least Australian academics includes the number and quality of publications per year. In retrospect, I was probably naïve and I wouldn't do it now."

His comments cut to the heart of what observers have said is at the heart of ghostwriting -- professors are under pressure to publish papers, and to publish often, or see their careers suffer. So when someone comes along to help them get more publishing credits to their name, they agree.

In a column by Peggy Curran, the Montreal Gazette wondered if the pressure to publish was behind the involvment with ghostwriters by McGill University professor Barbara Sherwin.

In a written statement last weekend, Sherwin said she “made an error in agreeing to have my name attributed to that article without making it clear that others contributed to it.” Sherwin said she was not paid for the article, and believes the article reflected “sound and thorough scholarship.”

So was Sherwin duped or simply sloppy, so desperately keen to publish she was willing to blur the lines of ethical conduct? If, as she says, the article went through a peer review, why didn’t she mention the other authors? How often do academics, under pressure to deliver on deadline, rely on a ghost for hire?

Jocalyn Clark, a University of Toronto assistant professor of medicine and a senior editor at PLoS, says universities have a responsiblity to get tough on ghostwriting. PLoS, along with the New York Times, managed to get 1,500 court documents on ghostwriting made public, and then put them online.

Canadian named in ghostwriting, part 2, and what can be done

In a story in this morning's Toronto Star, I explore the ties between McGill University professor Barbara Sherwin, alleged in court documents to have used a ghostwriter for an April 2000 study, and New Jersey ghostwriting firm on a second study published three years later.

Sherwin vehemently denies there was any ghostwriting involved in the 2003 article.

Here is her complete statement to the Star on the matter:

"Concerning the article in question, published in Endocrine Reviews in April 2003, I had refused to submit material offered by DesignWrite personnel. The article eventually published in Endocrine Reviews was entirely my own work. I cannot emmphasize that strongly enough."

"In my previous statement, I maintained that I had never - either prior to or following the publication of an article in the Journal of the American Geriatric Society in April 2000 - submitted work other than my own. I stand by that statement."

McGill continues to investigate. Here is the university's complete statement yesterday from provost Anthony C. Masi:

"As I said last week, McGill University takes academic integrity very seriously. We have policies and procedures in place that require us to investigate serious allegations of academic misconduct."

Jocalyn Clark, a Toronto-based senior editor for PLoS Medicine, which last month managed with the New York Times to get the court documents released to the public. says universities need take the lead in stamping out ghostwriting.

Academic institutions, she says, use a professor’s publishing record as the basis for promotions, grants and deciding who gets tenure – so have a responsibility to ensure those records are beyond reproach.

“Publications are the main currency in academic institutions,” Clark, an assistant professor at the Unviersity of Toronto medical school, said in an interview.

As such, the schools need to send a clear message that using ghostwriters will hurt an academic’s career, not help.

“Stamping out ghostwriting will only happen when academic institutions, their medical schools and their faculty declare that this is not acceptable,” she says.

PLoS, which in a recent editorial referred to ghostwriting as "the dirty little secret of medical publishing," has also called on medical journals to retract all ghostwritten articles, to notify the universities where the authors of the articles work and to ban those authors from publishing with that journal again.

Such measures, Clark says, could damage a researcher’s career. At that, she hopes, would be a powerful incentive for them to stay away from ghostwriters. 

PLoS has also made the court documents available online.
 

Ghostwriting documents a wealth of information

Court documents put online last week by PLoS Medicine give the public an unprecedented look into the world of academic publishing and the extent to which big drug companies used ghostwriters to market their products.

The 1,500 documents -- internal memos, meeting agendas and minutes, project tracking report, faxes, cover letters, draft manuscripts and more -- detail the efforts by Wyeth Pharmaceuticals to use top academic journals as marketing tools for its hormone replacement therapy drugs, and to enlist top researchers from around the world to be "authors" of the studies.

The documents were made public last month after PLoS and the New York Times convinced a US court ot unseal documents in a lawsuit to release them to the public. PLoS put them all online last Friday.

Toronto-based senior editor told me yesterday that the public needs access to these document so they can see for themselves what happened.

"The thing that strikes me about the documents is how the campaign is so co-ordinated, so deliberate," Jocalyn Clark says. "Which implies it is a normal course of business."

One document, a May 15, 1997 proposal by DesignWrite to produce ghostwritten articles for Wyeth, bluntly states three main goals for the partnership: boost physician awareness of HRT, “diminish the negative perceptions associated with estrogens and cancer” and lessen the competitive threat of another company’s similar drug.

The proposal, which won DesignWrite a seven-year contract to produce up to 30 articles at up to $25,000 per article, offers Wyeth (referred to as “the client”), full control over the content of the articles.

“After the client has reviewed and released the manuscript for submission, DesignWrite will see it through the necessary production stages – creating camera-ready figures and tables and the text according to journal guidelines and submit the package (manuscript, art cover letter, and any required forms and checklists) to the appropriate journal editor.”

Depositions by several DesignWrite and Wyeth executives are also among the doucments available.

In one such deposition, Karen Mittleman, senior medical writer at DesignWrite, explains the general process for ghostwriting: Wyeth sends data to DesignWrite to be used in a ghostwritten article. An outline is prepared by DesignWrite and sent to Wyeth for review. It then goes back to DesignWrite to prepare a first draft, which takes between four to eight weeks. The draft is sent to Wyeth for review and to a respected researcher in the field, who will also review it and attach his or her name as author.

In many of the documents, a distinction is drawn between “writers,” the anonymous people who pen the articles, and “authors,” the academics who lend their names and reputations to the finished product.

Beyond ghostwriting, the documents indicate, DesignWrite was also hired by Wyeth produced PowerPoint slides to be used by academics when making presentations at industry conferences. Wyeth paid $10,000 for this service.

Trudo Lemmens, a professor of law and medical ethics, has said such help with presentations is often the beginning of the slippery slope drawing academics into a pharmaceutical company’s sphere.

DesignWrite also wrote articles for academic journal supplements at $25,000 apiece, the court documents indicate. Wyeth could then by up multiple copies of the supplements for distribution to doctors’ offices and to give to its sales force to use as evidence of the effectiveness and safety of hormone replacement therapy.

The firm was also instrumental in putting together a patient information handout for doctors to give their patients if they had questions about HRT. The 2001 handout, written by DesignWrite writer Bernadette Janas and sent to Wyeth for approval, reassured women that “HRT does not increase breast cancer risk.”

No mention was made of the role DesgnWrite or Wyeth played in putting the handout together.