Research ethics need an overhaul: report

A report out this week calls for an overhaul of the way academic research is done in this country, and for an ombudsman to be appointed to oversee everything.

The report, the Montreal Gazette points out, was well underway before the question of academic integrity broke wide open in Canada last summer with a Toronto Star story about the use of ghostwriters by McGill University professor Barbara Sherwin in an academic article about hormone replacement therapy.

A university inquiry into Sherwin is still several months from completion, the schools says, and likely won't be finished until the new year. The school's provost office blames the long investigation on the huge repercussions for whatever it decides and the complexity and rarity of the case itself.

The new report, however, makes the point that academic misconducts are not all that rare -- though Canada is better than many. The drug sector is particularly bad.

Breeches of research integrity are a problem in some parts of the private sector, notably in the pharmaceutical industry. The existence of companies, including some in Canada, that “ghost write” papers for academic researchers is but one visible manifestation of research misconduct in the private sector. These companies craft research papers in support of a particular drug and seek out researchers willing to be listed as authors in exchange for money and other benefits.

The study, The State of Research Integrity and Misconduct Policies in Canada, prepared for the Canadian Research Integrity Committee by consulting firm Hickling Arthurs Low, says ghostwriting is only part of the problem.

The existence of companies, including some in Canada, that 'ghost- write' papers for academic researchers is but one visible manifestation of research misconduct in the private sector. These companies craft research papers in support of a particular drug and seek out researchers willing to be listed as authors in exchange for money and other benefits.

The report also looks at fabrication of data, falsification of data, plagiarism, conflicts of interest and abuse of power or retaliation towards colleagues and assistants. The 29 academic institutions surveyed, which represent about 60 per cent of the research done in Canada, reported investigating about 39 such incidents a year.

The report says that number is probably low.

This estimate should be treated with the appropriate caution given the challenges associated with collecting this information. In addition to research institutions having little incentive to share this information, there is a strong likelihood that misconduct cases go unreported by researchers due to an unwillingness to risk one’s own reputation or sour relationships with colleagues, or simply an unwillingness to engage a process that can lead to frustration and additional work stress. Under-reporting also comes about when allegations are reported but are then ‘swept under the carpet’ at some level of the institution. Anecdotes from interviews conducted for this study attest to all of these instances.

 

First Paxil trial goes to the jury

The first of some 600 civil trials to be held alleging that GlaxoSmithKline's anti-depressant causes birth defects was put in the hands of a Philadelphia jury this morning.

Testimony in the state-court trial, which began in September, wrapped up yesterday. Jury deliberations have begun and a verdict is expected sometime in the coming days or week, court watchers said.

The lawsuit involves allegations from Michelle David, who claims drug maker GlaxoSmithKline concealed negative study results linking Paxil to a life-threatening heart malformation in newborns of women who took the drug during pregnancy. The company marketed Paxil for treating pregnant women with anxiety, despite knowing about the apparent connection to birth defects, David contends.

David took Paxil while pregnant with her son, Lyam Kilker, who was born with life-threatening heart defects. The boy is now four and has fully recovered after being hospitalized as a newborn and undergoing multiple surgeries to repair his heart.

The trial is considered a test case for 600 such lawsuits expected to be heard the coming months in Philadelphia, where Glaxo's US headquarters are located. Lawyers for several of those upcoming cases have been in Philadelphia monitoring the David/Kilker case as they prepare their own arguments.

In his closing statement, David's lawyer Sean Tracey said Glaxo intentionally ignored the possibility that Paxil caused birth defects.

Glaxo researchers never followed up on studies showing Paxil posed a birth-defect risk for fear of harming sales, Sean Tracey, lawyer for a family suing over the drug, told jurors yesterday in state court in Philadelphia.

The London-based drugmaker “made a concerted effort” not to study Paxil’s links to birth defects, Tracey said. Glaxo executives sought to “avoid doing studies that would have revealed the truth about their drugs,” he said.

The drug, approved for use in the U.S. in 1992, generated about $942 million (US) in sales last year.

In her closing statement, Glaxo lawyer Chilton Varner urged jurors to “set sympathy aside and decide this case fairly,” adding that arguments that Glaxo “has acted improperly or unethically” in its testing and marketing of Paxil “don’t ring true.” 

She said the company isn't liable for Kilker's heart defects.

The company has set aside $2.8 billion to deal with legal and other non-tax disputes.

A second Paxil case, expected to begin next Tuesday, was settled out of court last weekend. The next is not scheduled to begin in mid-November.

 

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.”

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.

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.