'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.

Payments to doctors going online

Merck will soon become the largest drug company to post its payments to doctors online in the wake of costly lawsuits in which such payouts have become a big issue.

Richard Clark, chairman and chief executive of the second-largest US drugs group by sales, told the Financial Times that “the system needs to be totally transparent.” He also questioned whether there was a need for an annual ceiling on payments.

The group will begin publishing regular details in the fourth quarter.

His comments mark the latest escalation in efforts by drugs companies scrambling to seize the initiative on reforms to a system that has come under intense criticism for potential conflicts of interest, triggering growing legislative and regulatory pressure for change.

Critics claim tens of millions of dollars a year paid by drug companies in consultancy, speaking and writing fees as well as free drug samples given to influential doctors and medical academics are leading to prescriptions of medicines that are not justified by scientific evidence.

Merck isn't the first to do this Eli Lilly has alread set up its online registry, listing some $22 million (US) in payouts to 3.400 doctors and researchers in the first quarter. It was required to make the information publc after a $1.4-billion settlement in January over illegal promotion of its anti-psychotic drug Zy-prexa.

I took a quick look through the Lilly list. It's a bit overwelming. The doctors and researchers are listed alphabetically. The list is searchable, but it can be tough to find information unless you've got a good idea of what you're looking for.

The registry only includes US doctors, howsever, so there are no Canadians listed.

The Boston Globe, however, has used the list to find 60 Massachusetts doctors who received payments from Lilly.

At least 60 Massachusetts doctors collectively have earned more than a half-million dollars this year as speakers paid by pharmaceutical giant Eli Lilly & Co. - including two Boston Medical Center physicians whose participation is being reviewed for possible violation of a hospital policy against marketing activities by its doctors.

After learning of the doctors’ company-sponsored talks from the Globe, Boston Medical Center said it would investigate the matter and directed the physicians not to make any further presentations on behalf of Lilly in the meantime

A medical writer's perspective on ghostwriting

Montreal-based medical writer Kate Johnson has weighed in on her blog about the ongoing ghostwriting scandal, saying a distinction needs to be made between anonymous writers hired by drug companies, and those hired by the researchers themselves.

It's a fair point, and Johnson goes to lengths to explain how academic journal articles can have several authors, named and unnamed.

Obviously, if four names appear on a paper, it is unlikely that all four people sat down and typed individual sections. As a medical editor I strongly discourage this degree of “co-operation” because of the disjointed and chaotic results. But it is when an additional, unnamed person is responsible for the writing, that the notion of ghostwriting takes shape.

The ghostwriting scandal revealed in August by the New York Times hinges on this type of ghostwriting, but here a further distinction should be made regarding the definition of ghostwriting.

Although the JAMA study does not make this distinction, the Times focuses on ghostwriters who were hired by drug companies to spin the science in favor of their products. This is clearly a corruption of science and an indisputable attempt to mislead doctors and the public.

Few medical academics could see anything except extreme dishonesty in this practice.

The only point I might quibble with Johnson is on her use of the word "obviously" at the beginning of the excerpt. I am not sure this is obvious to most people, but I could be wrong.

She is right, though, that there is a difference between ghostwriters paid by a drug company and those paid by a researcher -- especially since the drug companies have made clear in their internal documents (made public in court cases) that paying ghostwriters is part of their drug marketing strategy. One would expect that ghostwriters hired by the researchers themsleves would be more attuned to the researchers' findings than to the marketing needs of Big Pharma.

Johnson has pointed out before that many top researchers, for all their brilliance and innovation, are not the best writers -- so turn to people like her for help. As a reporter who has had to sift through many scientific reports, I appreciate that contribution.

But I would also like to know that such a contribution has been made. From a reporter's point of view, there's no such thing as too much information when it comes to such things. It also erodes a researcher's credibility if, and when, it is revealed that a ghostwriter has been used and not acknowledged.

Perhaps researchers, when considering how much (if any) credit to give to ghostwriters should ask themselves one simple question: would I accept such behaviour from one of my students?

Wyeth ghostwriting documents now searchable

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. Here's a blurb on what the site is all about, how it got started, and how it is funded:

The Drug Industry Document Archive (DIDA) was created by the Center for Knowledge Management at the University of California San Francisco Library in collaboration with faculty members C. Seth Landefeld, MD and Michael Steinman, MD to house material pertaining to United States of America ex rel. David Franklin vs. Parke-Davis, Division of Warner-Lambert (now owned by Pfizer, Inc). Filed by former Parke-Davis employee David Franklin, the lawsuit alleged that the company violated federal regulations by engaging in systematic efforts to promote the drug gabapentin (Neurontin) for uses not approved by the U.S. Food and Drug Administration. Drs. Steinman and Landefeld were unpaid expert witnesses on behalf of the plaintiff and wrote an expert report for the court regarding marketing practices for gabapentin and its potential impact on physician prescribing.

Documents were obtained from public-access files of the United States District Court for Massachusetts and other sources including the plaintiff's law firm. These include materials written by Parke-Davis and companies with whom it worked which were entered as evidence, and legal documents outlining the progress of the litigation.

Documents from additional sources, including court cases and US government committee investigations, have been added to DIDA over the last few years. For a full listing of these sources, see The Documents.

The archive was founded with the support of a gift made by Thomas Greene to The Regents of the University of California in February 2005. Mr. Greene's law firm represented Mr. Franklin in the litigation from which many of the archived documents were obtained.

The Wyeth documents detail the use of ghostwritiers by Wyeth to promote its hormone replacement therapy drugs over the last decade. Last month, MecGill professor Barabara Sherwin was implicated in the case, when documents showed she used the services of a ghostwriting company on at least two occassions. Sherwin has denied any wrongdoing.

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.

Fighting Big Pharma a 'conflict' for journals

A study presented last week at the Sixth International Congress on Peer Review and Biomedical Publication found that academic journals can pay a heavy price if they crack down on industry-backed research.

The Journal of the American Medical Association saw a 21 percent drop in industry-financed research after it began requiring that data in company-sponsored medical trials be independently verified by university researchers, a study has concluded. 

The study, by a team of medical researchers in England and Florida, found that two of JAMA's competitors saw their proportions of industry-backed research grow after JAMA decided to impose the requirement in 2005 to deter companies from shading descriptions of medical-test results to favor their products. 

The findings suggest JAMA could face significant financial pressure to abandon the policy, given the reliance of medical journals on corporate dollars, said one of the study's authors, Benjamin Djulbegovic, a professor of medicine and oncology at the University of South Florida. 

"Major medical journals face an inherent conflict of interest" when trying to ensure the integrity of their published findings, Dr. Djulbegovic said in presenting the findings at the International Congress on Peer Review and Biomedical Publication here, a quadrennial conference of medical-journal publishers organized by JAMA with support from several of the other journals.

The conference also heard the depressing news that efforts to fight questionable research is having limited success.

Even some areas of improvement were shown to have their limits. About 300 journals have now joined a commitment by JAMA and other leading journals to publish only research in which the authors registered their intended outcomes in advance. 

The system, using either the federal registry or a recognized alternative, is designed to guard against researchers' using their studies to selectively identify data that support a drug or treatment rather than sticking to the criteria they initially promised to measure. 

But studies presented in Vancouver showed that the registry system isn't yet having a significant effect because too many researchers are making registry entries that are either vague or filled with too many measurement criteria. 

"Registration alone cannot improve research quality," Deborah A. Zarin, director of the federal registry, told the conference.  

JAMA also found its competitors still unwilling to join its commitment to publish industry-supported studies only if the data get an independent review.

The fingerprints of ghostwriting

At a conference of journal editors last week, the head of one publication said the electronic fingerprints left on documents as they pass from one use to the next can help weed out ghostwritten articles.

It's called metadata, a feature of Microsoft Word that identifies each person who uses and changes a document as it is transferred from one person to the next.

Frederic Curtiss, editor-in-chief of the Journal of Managed Care Pharmacy, told Reuters Health that data attached to documents by Word has allowed him to discover undisclosed contributors. In one case, for instance, a revised manuscript arrived at his office with four named authors, but when he examined the metadata, he discovered an additional author was making substantial contributions.  

When documents are saved in Word, the software attaches additional information, called metadata, which identifies the creator of the document. During the editing process, changes made by additional authors are also sometimes labeled with authors' names. Curtiss estimates that every third manuscript he receives has metadata that doesn't match listed authors, which can subsequently result in contributors being added to the acknowledgments, or, rarely, as additional authors.

That one-third is much higher than the 12 per cent figure released in a study released at the Sixth International Congress of Peer Review and Biomedical Publication in Vancouver where Curtiss was speaking. That study, however, relied on researchers admitting they used a ghostwriter. Other studies have pegged the rate of ghostwriting at more than half the articles in major journals.

As for the metadata, Curtiss said ghostwriters, and the researchers using them, are catching on.

Unfortunately, says Curtiss, he is losing the lead in the battle against ghostwriting. Sometimes, the metadata includes only the word "Author" or a number. "Now people are savvy about it," Curtiss says. "We are getting manuscripts where they have purposely removed data from the identification box."

In other words, this is no silver bullet.

Authors admit to ghostwriting

A study released this morning has found a high level of ghostwriting among the world's top medical journals, the New York Times is reporting.

Six of the top medical journals published a significant number of ghostwritten articles in 2008, according to the study by a researcher and editors at the Journal of the American Medical Association.

Among authors of 630 articles who responded to an online questionnaire designed by the researchers, 7.8 per cent acknowledged contributions to their articles by people whose work should have qualified them to be named as authors on the papers but who were not listed.

The prestigious New England Journal of Medicine had the highest rate, at 10.9 per cent. The Journal of the American Medical Association had a ghostwriting rate of 7.9 per cent, according to the study, released in Vancouver as journal editors gather to discuss ghostwriting.

Past studies have estimated much-higher ghostwriting rates, with some researchers saying their independent research foudn that more than half of the articles in some journals are ghostwritten. Today's study, however, relied on authors responding to an online survey, rather than a random sampling of researchers typically used in surveys, the Times points out.

Still, the researchers behind it said they hoped that the study will push journals to address the issue.

“These journals are the top of the medical field,” Joseph S. Wislar, the lead author of the study, said in a phone interview Tuesday.

He recommended that medical journals take more action to require that all contributors be listed in acknowledgments if they are not named as authors.

“Journals are really just starting to dig into that, and we’re hoping that’s going to help,” Mr. Wislar said. “We haven’t seen that help yet.”

Medical journal examines ghostwriting

Canada's top medical journal, the Canadian Medical Association Journal, takes a look today at the risks involved with ghostwriting, following up on the case of McGill researcher Barbara Sherwin.

The Toronto Star last month revealed that Sherwin was listed as the sole author on a 2000 article on hormone replacement therapy, without revealing that she had been helped by ghostwriting firm DesignWrite. The firm had been hired by drug company Wyeth to promote its HRT products. She also worked with the company three years later, though she denies she used any of its contribution in the 2003 article.

In its article today, the CMAJ says the revelations were the tip of the iceberg.

Somewhere between 50% and 100% of articles on drugs that appear in journals are ghostwritten,” says Dr. David Healy, a psychiatrist at the University of Cardiff in Wales, United Kingdom, and a critic of the drug industry's influence on physicians’ drug prescribing habits.

Healy says that ghostwriting “crept up on” the medical profession and became so common by the mid-90s that even senior researchers came to accept it as an ethical practice. Other critics of the practice agree, claiming that many researchers will put their name on a document as primary author even if they just edited it — or only read it and made no changes.

“If you have people like me who say they can’t do this, the pharmaceutical industry can easily go elsewhere and find a person who will,” says Healy.

Ghostwriting has been able to spread, the article says, because all three groups involved -- drug companies, academics and medical journals -- benefit.

Transparency advocates say ghostwriting has become commonplace because it provides substantial benefits to three parties: drug companies, researchers and medical journals. By managing the publication of articles about their products, it is easier for drug companies to spread positive results and bury negative results. This often provides a big boost to drug sales. Having the name of a “key opinion leader” on a study is even better, ghostwriting critics say, because it gives the study an air of independence and respectability.

Many academics show little reluctance in lending their names to articles someone else wrote because it pads their resumes, which tends to help them bring in more money on the lecture circuit, says Arthur Schafer, director of the Centre for Professional and Applied Ethics at the University of Manitoba in Winnipeg.

“They sold their credentials for false credit and money,” says Schafer.

As for medical journals, they benefit by gaining access to papers on the latest clinical trials for new drug products. Some even accuse medical journals of pandering to the pharmaceutical industry, including turning a blind eye to ghostwriting, so they can publish clinical trial results.

 The article quotes critics calling for more transparency in who writes journal articles and details of their contributions, but does not say what CMAJ will do. As the CMAJ notes, ghostwriting will be a major topic at a meeting of journal editors next weekend in Vancouver.
 

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.

Conflicts of interest can hurt business

The chief executive of medical device maker Medtronic Inc. was forced during the company's annual meeting yesterday to defend his company's million-dollar deals with university professors and other researchers hired as consultants.

Medtronic is at the centre of a growing scandal over the close ties between medical and pharmaceutical companies and the researchers who are supposed to be testing their products.

At the annual shareholder meeting of Medtronic Inc. Thursday, CEO Bill Hawkins defended the company's longstanding practice of collaborating with physicians, although he acknowledged these paid relationships could pose a conflict of interest.

Working with doctors to improve devices and commercialize inventions is crucial to advancing medical technology, Hawkins said before a crowd of about 400 people at the company's Fridley headquarters.

Yet these relationships have triggered inquiries by Congress and the Department of Justice, prompting a pointed question from one shareholder who said he was shocked at the amount of money paid to Medtronic's doctor consultants.

Recent reports have focused on the consulting relationship between Medtronic and Dr. David Polly, the head of spine surgery at the University of Minnesota. Between 2003 and 2007, Medtronic paid Polly $1.2 million for consulting, expenses and honoraria.

The shareholder, 77-year-old John Burbidge of Edina, Minnesota, said that while he understood the need for input from physician consultants, he was "taken aback" by the sums of money involved.

Is it really necessary to pay that kind of money to doctors in order to get good information?" he asked.

"Can you rely on information that you pay that much money for?" added Burbidge, who said he is a longtime Medtronic shareholder.

"Obviously, nobody is going to want to tell you anything you don't want to hear and jeopardize his relationship with the company."

The university of Minnesota is investigating Polly's links to Medtronic to see if they violate school policy.

Meanwhile, it would seem that quarterly profits at the company dropped almost 40 per cent do to leagal costs, and the price of its shares fell.