A Stand for Scientific Independence Medical Journals Aim to Curtail Drug Companies' Influence

By Susan Okie Washington Post Staff Writer Sunday, August 5, 2001; Page A01

Editors at the world's most prominent medical journals, alarmed that drug companies are exercising too much control over research results, have agreed to adopt a uniform policy that reserves the right to refuse to publish drug company-sponsored studies unless the researchers involved are guaranteed scientific independence.

The New England Journal of Medicine, the Lancet, the Annals of Internal Medicine and the Journal of the American Medical Association (JAMA) are among the journals that have agreed to publish a joint editorial in mid-September outlining the new policy, which was drafted by a committee of editors over the last several months.

The unprecedented move could have a significant impact on how medical research is conducted and reported by giving researchers more leverage in their dealings with the pharmaceutical industry. Companies are eager to publish studies in these prestigious journals because doctors view them as credible sources of information to help them decide which drugs to prescribe to patients.

Editors said the new policy is a response to companies' increasingly tight hold over how research is done -- and, in many cases, over whether and how the results are made public. In recent years, drug companies have become the dominant funder of biomedical research, especially of large studies of medicines' safety and effectiveness.

The authors who receive top billing on drug studies published in respected, peer-reviewed journals are usually medical school professors who are experts in their fields, but much of the research is paid for, and in large measure carried out, by companies with an enormous financial stake in the outcome. Company employees usually collect and analyze the data, and they often decide how it should be presented and write the reports.

The journal editors decided to act after several recent cases involving charges that drug companies tried to withhold research results or present them in the most favorable way, several said during interviews last week.

"It's become a huge problem," said Frank Davidoff, who as editor of the Annals of Internal Medicine was among those who decided to take a stand on the issue at an international meeting of medical journal editors in May in Philadelphia.

Catherine D. DeAngelis, the editor of JAMA, said her journal already has a policy of demanding that study authors vouch for the integrity of their data. "The goal would be that all of the major journals would adopt similar . . . principles," she said.

Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine, confirmed that the editorial is to be published in mid-September but declined to discuss its content other than to say "it's an important issue."

The decision was praised by several observers of biomedical studies who have become alarmed about the influence of the drug industry on the integrity of medical research.

In large, company-sponsored drug trials involving multiple hospitals, all of the information collected is typically held by the company, said Marcia Angell, former editor in chief of the New England Journal of Medicine. "Not even the principal author sees all the data," she said.

As editor of the journal, Angell recalled, she sometimes received manuscripts from company-sponsored studies that had the "methods" section -- the explanation of how the study was carried out -- left blank. "They'd say, 'This is proprietary,' " she said.

Surveys of the medical literature have shown that studies paid for by drug companies are more likely than those with other sponsors to show results favorable to the product tested, said Lisa Bero, a professor of clinical pharmacy and health policy at the University of California at San Francisco.

Many medical schools include clauses in grant agreements with companies stating that researchers will be free to publish even if the results are negative. "But even if you have one of those, you can still get hassled, still get pressure put on you for fear that you won't get any future funding," Bero said.

Bert A. Spilker, senior vice president for scientific and regulatory affairs at the Pharmaceutical Research and Manufacturers of America (PHRMA), called the journal editors' concerns "patently absurd."

"The journals are becoming more and more antithetical to even considering an industry perspective," Spilker said. Academic researchers participating in studies "are given every opportunity to review, make suggestions and sign off" on manuscripts, he said. "Except for some very, very rare exceptions . . . [the process] is working very well."

Spilker said companies often control access to data and decide who writes the article. "It is often easier for the sponsor or a contracted group to write the paper," he said. "The most common situation is that the academics are too busy to take all the time needed to create the publication."

Robert J. Temple, director of medical policy at the Food and Drug Administration's Center for Drug Evaluation and Research, said, "One of the things I learned a long time ago is that the person who writes the rough draft has a lot of control.

"What the journals have to figure out is, if that's the way it's done, should it be explained that way? Should the senior author say, 'This was drafted for me, but I believe it?' " he said.

The journal editors decided to issue the joint editorial in response to "three or four well-known egregious examples, and many less well-known" cases in which companies tried to block publication of unfavorable studies or tried to put a positive spin on the findings, said Davidoff, who stepped down as editor of the Annals in July.

In a case last year, researchers at the University of California at San Francisco defied a corporate sponsor by publishing a study concluding that Remune, a vaccine-like product developed as an HIV therapy, did not benefit patients who were already receiving standard treatments. The company, Immune Response Corp. of Carlsbad, Calif., is seeking $7 million to $10 million in compensatory damages from the university for harming its business.

University of Toronto physician Nancy Olivieri lost her research contract with Apotex Inc., a Canadian drug company, after she spoke out and published an article in 1998 about a serious side effect of deferiprone, a drug for a blood disorder. Olivieri's contract with Apotex contained a non-disclosure clause. Elie Betito, director of public and government affairs for Apotex, said Olivieri's contract was terminated because she failed to follow the protocol specifying how the study should be carried out, not because she published her findings.

In the early 1990s, UCSF pharmacologist Betty J. Dong found that cheaper generic versions of thyroid hormone worked as well as Synthroid, the brand-name drug whose maker had funded the research. The company, Knoll Pharmaceuticals, successfully blocked publication of Dong's findings for seven years. In 1999, Knoll agreed to pay 37 states almost $42 million to settle a suit alleging that it had made false claims that Synthroid was superior to competing brands and had interfered with the publication of the study.

James Wright, a professor of clinical pharmacology at the University of British Columbia, predicted that if medical journals take a stand in favor of scientific independence, it will have an impact on drug companies' behavior. "The company wants [its drug] to be in one of these prestigious journals," he said. "All they need to do is say, 'We won't publish it unless it has all the information.' "

-- Anonymous, August 05, 2001