Medical Journal May Have Flouted Own Ethics 8 Times

The renowned New England Journal of Medicine--the world’s top-ranked medical journal and a leading voice in biomedical ethics--has apparently violated its own ethics policy numerous times in the last three years, publishing articles by researchers with drug company ties and not disclosing the potential conflicts of interest.

In an analysis of 36 “Drug Therapy” review articles since 1997, The Times has identified eight articles by researchers with undisclosed financial links to drug companies that marketed treatments evaluated in the articles.

The interim editor in chief, Dr. Marcia Angell, said in an interview Wednesday that the journal’s practices were at odds with its guidelines on financial conflicts of interest. “We’re going to try to do the right thing and bring our practice into conformity with our policy.

“There was a problem with the [‘Drug Therapy’] series. There was a misinterpretation of exactly what our policy was.” She said the journal had not yet had time to check all the articles identified by The Times.

The Times’ finding feeds into a larger social debate over the promotion of company-sponsored research done at academic medical centers, where the goals of seeking knowledge and earning profits may clash. And it highlights the expanding role that drug company funding and perquisites can play in some researchers’ careers, raising questions about impartiality that lie at the heart of scientific inquiry.

Also, because physicians rely on journals for unbiased information, arcane matters of financial conflict of interest may touch the lives of many patients. This is especially the case with the New England Journal: It ranks as the world’s most influential medical journal, according to the Institute for Scientific Information, which gauges a publication’s impact based on how often other publications cite it.

Among the articles questioned in the “Drug Therapy” series was a 1997 review of multiple sclerosis treatments. The lead author, Dr. Richard A. Rudick of the Cleveland Clinic Foundation, received research funds, speaking fees and travel expenses from three drug companies whose treatments were discussed in the article, he said.

In another instance, the sole author of a 1998 review of breast cancer treatments, Dr. Gabriel N. Hortobagyi of the University of Texas M.D. Anderson Cancer Center, said he had received consulting fees, research funds and speaking fees from multiple companies that make drugs assessed in his article.

Publication of those articles and several others goes against the journal’s famously restrictive conflict of interest policy: It “prohibits editorialists and authors of review articles from having any financial connection with a company that benefits from a drug or device discussed in the editorial or review article.”

Among the barred commercial ties are equity interest, consultancies and major research support, the journal’s guidelines say.

The Times conducted the analysis after reporting last month that the journal ran a review of hair-loss treatments by a researcher with undisclosed financial ties to the companies that market the popular drugs Rogaine and Propecia. Dr. Vera H. Price, a UC San Francisco dermatology professor, had served as a consultant to Pharmacia & Upjohn and Merck & Co. just before writing the review, and her research has been funded by the companies.

In a letter to be published in the journal next month, Angell and the editor who handles the “Drug Therapy” reviews, Dr. J.J. Wood, accept responsibility for the flap surrounding Price’s article and apologize for “any difficulty it has caused her.”

The letter, which Angell made available to The Times after questions about the “Drug Therapy” series, says the journal is “looking into the possibility that authors of other published articles in this series may have had financial associations with pharmaceutical companies that were incompatible with our stated policy.” Angell said their letter and one by Price may be posted as soon as today on the journal’s Web site (www.nejm.org).

The 187-year-old weekly has positioned itself as the leader on this ethics issue, with the top editors even daring others to adopt their high moral stance: “We hope that we will soon be joined in our policy by our sister journals,” they wrote in an October 1996 editorial.

Like other publications, the New England Journal allows researchers with company ties to present original new data derived from company-sponsored work; such articles disclose to readers the authors’ ties. But the journal supposedly disqualifies researchers associated with a company from writing editorials and reviews about its products because “the essence of reviews and editorials is selection and interpretation of the literature.”

Although that policy may be novel, The Times’ observation that about 22% of recent “Drug Therapy” articles were by researchers with undisclosed company ties is problematic, experts said.

“It’s highly misleading of journal editors to say on the one hand that they have a strict policy to avoid conflict of interest and then turn around and violate that policy,” said Mildred Cho, a scholar at the Stanford University Center for Biomedical Ethics who has studied journal practices and policies.

Some medical researchers question the wisdom of the journal’s restrictive policy, given that the leading authorities on drug treatments often are clinicians whom drug companies seek out to investigate new products.

For the analysis, The Times researched the authors of the 36 “Drug Therapy” reviews since 1997. Sources included government documents, academic and industrial Web sites, company news releases, medical journals, conference proceedings, news reports and interviews.

The other instances of undisclosed drug company support to the authors are as follows:

* The coauthor of a January 1997 review of hepatitis treatments, Dr. Adrian M. Di Bisceglie of the St. Louis University School of Medicine, listed relationships with four drug companies--including research support, consulting fees and speaking fees--at a medical meeting the next year. Some of those companies make drugs covered in his review.

* A January 1997 review of vaccines for viral hepatitis was coauthored by Dr. Stanley M. Lemon of the University of Texas Medical Branch at Galveston. His academic Web site says he received vaccine-research funding from SmithKline Beecham Pharmaceuticals from the beginning of 1996 to the end of 1998. In addition, he had received research support from Merck & Co., he said in an interview.

* The lead author of a 1999 review of a particular type of asthma medication, Dr. Jeffrey M. Drazen of Brigham and Women’s Hospital in Boston, has received funding over the years from AstraZeneca PLC, maker of one of the drugs he reviewed, Accolate, according to a 1996 company news release.

All six authors mentioned above--Rudick, Hortobagyi, Price, Di Bisceglie, Lemon and Drazen--confirmed their drug company support in interviews and said they fully informed the journal about their financial associations.

Two additional articles in the journal were by authors based in Europe who did not respond to e-mail messages from a Times reporter seeking comment.

* Dr. Frits Holleman of Utrecht, Netherlands, coauthored a July 1997 review of the fast-acting insulin called lispro. His research has been funded by a company that makes the drug, Eli Lilly, according to a study he published that same year in the journal Diabetes Care.

* A 1997 review discussing treatments for Paget’s disease, a bone disorder, was written by two researchers at the French health ministry who had ties to Merck & Co., which markets Fosomax, a drug discussed in the article. Dr. Pierre D. Delmas has done consulting work and received research support, and Dr. Pierre J. Meunier had received research support, according to disclosures published elsewhere about that time.

Most of the researchers contacted by The Times said the New England Journal scrutinized their financial dealings more closely than any publication had ever done.

Any ethical inconsistency in the “Drug Therapy” reviews resulted from misunderstandings between the series’ editor, Wood, and the main office in Boston, Angell said.

According to the letter by Angell and Wood, Wood did not disqualify major research support paid to the university or medical center and then disbursed to the researcher’s lab. Nor did he routinely disqualify consulting arrangements if they ended when the article was assigned. Wood was traveling Wednesday and could not be reached for comment, his assistant said.

Those practices, Angell said, run counter to journal policy, which is meant to minimize the skewing of clinical data. “There is a lot of goodwill on the part of an author toward a company that he or she is working with closely,” she said. “And that can unconsciously bias the work.”

The Times’ analysis did not evaluate whether authors with undisclosed commercial support were more or less favorable toward the companies’ products than the evidence would warrant. But there is academic evidence that articles by company-supported authors tend to be positive toward their sponsors’ products.

For instance, a study in this week’s Journal of the American Medical Assn. found that researchers with drug company support were less likely to write negative cost-benefit analyses of new cancer drugs than were researchers who had no company support.

Financial conflict of interest concerns have prompted lively debate among journal editors in recent years. Some editors argue that such disclosures are of only marginal importance; that the clinical evidence speaks for itself, regardless of the funding source; and that dwelling on financial matters can obscure other, more significant sources of bias, such as the lure of fame or academic advancement.

But most journals require that researchers provide information on company ties before the editors decide what, if anything, merits disclosure to readers.

The New England Journal’s pioneering ethics policy has attracted public controversy before. In 1996, it published an editorial on diet drugs by two researchers who had served as consultants to companies involved in the drugs’ marketing. The researchers say they disclosed their ties to the journal. The journal then clarified its guidelines, disqualifying researchers with “consultancies” in general, not just “ongoing” or “regular” ones.

Now the journal is developing new ethics guidelines. Among other things, disclosure statements will run with editorials and reviews by authors receiving “minor” research support. “Authors of newly solicited and all future review articles will be held strictly to our stated policy,” Angell and Wood say in their letter.