January 17, 2005

Dispute Puts a Medical Journal Under Fire

ast year was an especially bad one for the pharmaceutical industry, which experienced controversies over how drug studies are disclosed and the implosion of the painkiller Vioxx. Now, as a result of the recent publication of an article about the antidepressant Prozac, it appears that the staid, usually methodical world of medical journals could suffer its own black eye.

On New Year's Day, the British medical journal BMJ published a news article suggesting that "missing" documents from a decade-old lawsuit indicated that Eli Lilly & Company, the maker of Prozac, had minimized data about the drug's risks of causing suicidal or violent behavior.

Within days, the article was cited in hundreds of television and newspaper reports. An outraged Washington lawmaker demanded to know if Lilly had hidden the information from the Food and Drug Administration. While company officials refuted the article's assertions, it was still repeatedly cited. And last Thursday, Lilly spent about $800,000 to run full-page advertisements in 15 major publications to dispute the article.

The incident may prove to be a messy one for the BMJ, which is based in London and owned by the British Medical Association, a professional group. Much of the journal, formerly known as the British Medical Journal, is devoted to research reports about medical issues that are reviewed by experts. But the BMJ, like some other medical journals, also has a separate news section that prints articles like the recent one about Prozac. As it turns out, some of the Eli Lilly documents, which the BMJ said it received from an anonymous source, have been circulating for years. And, Lilly officials said, the BMJ and its reporter declined to provide the company with copies of the documents at issue prior to the article's publication.

The American freelance reporter who wrote the article, Jeanne Lenzer, declined to be interviewed, referring all questions to the BMJ. Officials there did not respond to written questions, but a spokeswoman, Emma Dickinson, said in an e-mail message on Friday that the publication "takes this issue very seriously" and will address Lilly's concerns after reviewing them.

The BMJ, which is considered a leading medical journal, may have little choice. While Lilly has not taken legal action, its lawyers have notified the publication that the company considers the article to be "inaccurate and defamatory," asserting that the records were not missing and that all their relevant data had been previously submitted to the F.D.A. Also, Lilly issued an analysis last week of the 52 pages of records that the BMJ had received, which the company said supported its claims. Lilly said it got the documents from a congressman who received them from the BMJ.

"You put something out on the newswire with the imprimatur of a medical journal and people think it is fact," said Dr. Alan Brier, the chief medical officer of Eli Lilly, which is based in Indianapolis.

The article's appearance follows the recent controversy over whether drug makers adequately disclosed the risks that antidepressants like Prozac posed to pediatric patients. And its comes as a South Carolina teenager faces trial for murder as an adult on charges that he killed his grandparents when he was 12. The teenager, Christopher Pittman, has acknowledged the crime, but his lawyers have based his defense on the argument that he became violent after taking the drug Zoloft, an antidepressant similar to Prozac.

It was in a little-noticed article written by Ms. Lenzer in the Dec. 11 issue of the BMJ about the Pittman case that she first mentioned that the publication had received "a set of documents that mysteriously went missing from a U.S. mass murder case ten years ago."

That article did not go into specifics. But in her article on Jan. 1, Ms. Lenzer wrote that the documents in question were connected to a Prozac-related lawsuit that grew out of a shooting rampage in 1989 by a Kentucky man, Joseph Wesbecker, that left nine people dead, including Mr. Wesbecker.

Lawyers representing the victims sued Lilly, asserting that Mr. Wesbecker's killing spree was caused by Prozac, a drug he had been prescribed just before the crimes. During the 1994 trial of the case, Lilly pointed to Mr. Wesbecker's long history of severe psychological problems and said that Prozac was safe.

To combat those assertions, plaintiffs' lawyers introduced hundreds of Lilly documents. They argued that the records showed that Lilly had fully disclosed to the F.D.A. in the late 1980's the potential of Prozac to produce suicidal thinking or acts of violence, including all the reviews by drug regulators in Germany of the issue at that time. Lilly disputed that.

The jury found in favor of Lilly. But a legal controversy over the trial later erupted when it was revealed that plaintiff lawyers and Lilly lawyers had reached an undisclosed financial deal just before the case went to the jury to effectively settle by agreeing not to appeal the verdict.

A Lilly spokesman, Phil Belt, said that Ms. Lenzer, who lives in Kingston, N.Y., first contacted the company on Dec. 13, a few days after her article about the Pittman case appeared.

Mr. Belt said Ms. Lenzer asked where a published report about the data in a specific 1988 internal Lilly report had appeared. At that time, she also requested an interview with the company's chief executive, Sidney Taurel, to discuss what she described as "missing" Lilly documents, Mr. Belt said.

Mr. Belt said the company told Ms. Lenzer that Lilly needed to see the records at issue before it proceeded. He added that Ms. Lenzer later told Lilly that she could not do so, saying that the source of the documents was anonymous.

As the Christmas and New Year's season approached, Mr. Belt said that Ms. Lenzer told Lilly officials that they could pick up the issue after the holidays.

At some point in December, however, Ms. Lenzer or her editors apparently sent the documents it had received to Congressman Maurice Hinchey, Democrat of New York, and to the F.D.A. And a few days before New Year's, the BMJ distributed Ms. Lenzer's article to other news organizations with the provision they could not write about it until its publication date on Jan. 1 - a practice known as an "embargo."

That article carried the headline, "FDA to Review 'Missing' Drug Company Documents," which caught the attention of other news organizations. Mr. Belt said that when Lilly became aware of the embargoed news release, it tried to reach editors at BMJ but was unsuccessful. Both Ms. Lenzer and the BMJ did not respond to written questions about the publication's interactions with Lilly, including why the documents were not shown to the drug maker.

The only Lilly document specifically mentioned in the BMJ article was a 1988 report that stated that 38 percent of depressed patients taking Prozac during clinical trials experienced side effects like agitation, insomnia and nervousness, a rate twice that of those taking a placebo.

Such side effects, which are sometimes referred to as "activation," reflect the fact that some depressed patients who take Prozac and drugs like it often experience a surge of physical energy well ahead of psychological recovery. Some experts have long expressed concerns that such reactions can be so severe in a few patients that they may ultimately act on suicidal or violent impulses.

For procedural reasons, the 1988 Lilly memo itself was not introduced as evidence in the Wesbecker case, said Nancy Zettler, one of the two plaintiffs' lawyers involved. But Ms. Zettler said that one of her expert witnesses, Dr. Peter Breggin, testified extensively about its contents at that trial.

Ms. Zettler said that she was so perplexed by the BMJ article that she contacted Ms. Lenzer after it appeared. "Her original article made it seem like we had deep-sixed some of this stuff and I was curious," she said.

Both Ms. Zettler and Paul Smith, the other plaintiffs' lawyer in the Wesbecker case, said that Ms. Lenzer did not contact them prior to the article to talk about the records or ask for others from that case.

Another plaintiffs' lawyer who has used Lilly documents in other lawsuits, Arnold Vickery, also said he did not discuss the records with Ms. Lenzer prior to her report. Mr. Vickery and another lawyer are representing Christopher Pittman.

Dr. Breggin has written articles arguing against the use of Prozac and other drugs and has mentioned the 1988 Lilly memo in his writings; he is scheduled to be an expert witness in the Pittman case.

Several pages sent to the BMJ were not produced by Lilly but are photocopies of slides produced by an F.D.A. official who presented them at a 1991 public hearing that reviewed the possible suicide risks of Prozac. After its review, that agency panel decided not to issue any additional warnings.

Ms. Zettler said she still thinks the issue of what Lilly told the F.D.A. in the mid-1980's about Prozac's potential risks is unsettled. But after more than 15 years of the drug's use, numerous lawsuits and public reviews, it may also be largely moot.

As a result of the recent controversy about the potential suicide risks posed by antidepressants to children and teenagers, the F.D.A. last week sent out final new labeling language about those dangers to all makers of such drugs, including Lilly.

A spokeswoman for the agency, which is still reviewing the records sent to BMJ, said that it had not yet found anything new in them. Ms. Dickinson, the publication's spokeswoman, said that it was reviewing Lilly's rebuttal to its article.