AIDS DRUG RESEARCHERS SAY
FIRM PRESSURED THEM

By Richard Saltus

Boston Globe 1 Nov. '00

It's just what traditionalists warned about as private investors took on an ever-growing role in US medical research: the company that pays for a drug study has the power to pressure scientists to make results look better than they are.

That's exactly what scientists from Harvard University and the University of California at San Francisco say happened to them when they tried to publish results from a massive AIDS drug trial. Offering a rare look at the politics behind modern science, the researchers say the biotech company that funded their study tried to put a positive spin on the results, then, when that failed, attempted to block publication altogether.

The study in its unaltered form appears in today's Journal of the American Medical Association, but the fight is far from over. The company that funded the study, Immune Response Corp., has filed a multimillion dollar binding arbitration claim against the University of California and the lead scientist, alleging damage to its business.

Officials of Immune Response ''really tried to stymie our efforts at communicating with our colleagues,'' Dr. James O. Kahn, the study leader, said in an interview. ''And finally they tried intimidation'' by filing the arbitration action seeking monetary damages.

In their defense, officials at the Carlsbad, Calif.-based company deny treading on scientific freedom. They say they tried in vain to get the researchers to include data that the company felt were relevant - and that some other researchers in the multicenter trial did, too. They say they only resorted to legal action when that failed.

But, as the clashes between researchers and their private backers over publication rights become more frequent, scientific organizations are reacting with alarm.

Cases like this ''are a major, major concern to us,'' said Irving Lerch, who heads a committee on Scientific Freedom and Responsibility for the American Association for the Advancement of Science.

''There are too many that have hit the public spotlight to make me think these are very rare events, and I think we have a problem we have to deal with,'' said Dr. David Korn, an official of the American Association of Medical Colleges.

The study involved 2,500 patients infected with HIV, the virus that causes AIDS, and was the largest AIDS drug trial of the 1990s. Immune Response, founded by the late polio vaccine pioneer Jonas Salk, wanted to test its ''therapeutic vaccine'' called Remune.

The company's hope - and the hope of the scientists who tested it - was that giving the vaccine to people infected with HIV would spur their immune defenses to slow or halt the progression to AIDS.

In 1995, Kahn, an associate professor of medicine and AIDS specialist at UC San Francisco, was chosen as the leader of a team that included Stephen Lagakos and Deborah Weng Cheng, biostatisticians at the Harvard School of Public Health, and Dr. Kenneth Mayer, an AIDS researcher at Brown University.

Begun in 1996, the research study was halted in 1999 when a monitoring committee determined that patients who got the Remune injections were faring no better than those who got standard antiviral drugs without Remune.

When it came time to write up the data for publication, Kahn, Lagakos, and others on the team concurred that the analyses showed no benefit from the drug. But scientists from Immune Response performed their own analysis of blood tests on a sample of 250 patients in whom, the company argued, some benefit could be seen - not in longer survival, but in having lower levels of virus in their blood.

Dr. Ronald Moss, the company's medical director, argued that those data should be part of the report manuscript.

''The Company never wanted to stop a publication - we just wanted it to be representative of the viewpoints of the other clinical investigators, as well as ours,'' Moss wrote in a statement. The goal was ''to present information we felt was important to include to the scientific community, and let people decide for themselves what the meaning was,'' he added in a telephone interview.

Kahn and the others, saying the analysis wasn't statistically sound, refused.

''The sponsor wanted a specific small piece of data included that they think shows their product works,'' Kahn said in an interview. ''We declined. We didn't think it was a valid analysis.''

In response, the company demanded the right to approve the researchers' manuscript before publication. They refused again.

Lagakos said: ''The company did not want our original analysis to go forward. We were put in a position where we had to agree to terms that were unacceptable to us. We decided to go forward with what we had.''

In September, Immune Response filed an action with the American Arbitration Association that attempted to block publication of the report, and sought damages of $7 million to $10 million from the university and Kahn.

The arbitration process has yet to begin, said Christopher Pitti, counsel for the University of California.

The AIDS study is just the latest in a string of disputes over the past several years pitting scientists' freedom of inquiry against rights asserted by their employers or commercial sponsors. In some cases, the scientists were required to sign ''nondisclosure'' agreements forbidding them to talk about their findings for a specified period of time.

In one high-profile case, a pharmaceutical company suppressed a finding by another UC San Francisco scientist that a popular thyroid drug, Synthroid, was no better than cheaper rivals. The study, originally to be published in 1995, was withdrawn by the authors following legal threats by the company, Knoll Pharmaceutical Co. It was finally published in 1997.