Thursday, June 23

Industry-funded Scientific Research - an Oxymoron?


Medical research has suffered a public-relations disaster in recent months. Leading arthritis drugs such as Vioxx and Bextra were pulled from store shelves when it was revealed that their makers and the federal government had overlooked deadly side effects. The National Institutes of Health came under fire when an investigation found that some of its researchers had received hundreds of thousands of dollars as consultants for drug companies. And a medical professor at the University of Vermont admitted to having made up data in dozens of federal grant applications and in published papers about, among other things, aging and obesity in women.

Those cases have sparked a public debate about ethics in research and whether academic medical researchers are truly independent of the companies that have a stake in their findings. Far from the headlines, however, corporate influence on another sort of health-related research runs even deeper, with little discussion among scientists, and meager scrutiny by watchdogs.

"There's not been a lot of debate," says Arthur L. Frank, a professor of public health and chair of the department of environmental and occupational health at Drexel University. "Most academics live in their ivory towers and do their own work: 'You leave me alone, I'll leave you alone.' It takes a certain amount of guts to stand up and say the emperor has no clothes."

Many academic scientists who work in occupational and environmental health -- a field dedicated to studying dangers to the public's health from the workplace and the environment -- say business interests increasingly drive research agendas.

"In this country over the last 20 years, the proportion of research studies that have been funded publicly has dropped substantially, and the proportion of privately funded has gone up," says Michael A. Silverstein, a clinical professor of environmental and occupational health sciences at the University of Washington. "It may be even more true in the area of environmental and occupational health," he says, because the federal agencies that provide funds for that research receive less money than many other institutes do.

The stakes are high. Academic researchers find themselves facing off as expert witnesses in multimillion-dollar lawsuits by neighbors of industrial sites, who say their cancers were caused by exposure to toxins. Scientists represent opposite sides in debates over protecting workers from radiation and protecting populations from polluted water and air. Meanwhile, lawsuits drag on for years, and the regulatory process grinds to a halt in the face of the experts' conflicting analyses.

Some researchers in these fields think any collaboration with industry taints the science. "This isn't a matter of minor ethics," says Joseph LaDou, a clinical professor of medicine at the University of California at San Francisco. "These are bought scientists."

But researchers who do work for industry dismiss such attacks. "You're not biased if you're correct," says Kenneth J. Rothman, a part-time professor of epidemiology at Boston University who consults for industry when he is not on the campus.

Regardless of their philosophy, scientists agree that their battles have substantial influence on public health.

"A tremendous amount of research is being done now clearly for advocacy purposes," says David M. Michaels, a professor of environmental and occupational health and of epidemiology at George Washington University. "Right now the money that's going into epidemiology is going into epidemiology to support litigation."

Money Talks Loudly

What critics see as a crisis in occupational- and environmental-health research is driven by two fundamental realities in the field: the lack of available money from the government, and researchers' dependence on industry for information.

Because their work is a low priority at government agencies that sponsor medical research, scientists are forced to look elsewhere for money.

For instance, the 2004 budget of the National Institute for Occupational Safety and Health for extramural research on workers' public health -- work done under the institute's auspices but not within its walls -- was $81.6-million. Environmental-health research fares relatively better: the 2004 budget for outside research at the National Institute of Environmental Health Sciences is $462-million.

But both figures pale in comparison with some of the better-financed areas of medical research. The National Cancer Institute, for instance, spent $3.7-billion on extramural research in 2004, while the National Institute of Allergy and Infectious Diseases spent $3.5-billion.

"The demand is probably greater than the funding that NIOSH has," says Richard A. Lemen, who was deputy director of the institute from 1992 to 1996.

Industry often fills the gap. An industry-sponsored study done 10 years ago of risks in just one field, semiconductor manufacturing, cost about "half the extramural research budget of NIOSH," says the academic scientist who spearheaded it.

By definition, practically any epidemiological study in occupational medicine will involve some industry participation. Environmental medicine has a similar tie -- researchers often want to know whether chemicals from an industrial site are affecting public health. Cooperation with industry can mean access to a facility's work force -- or to crucial data that wouldn't be available otherwise.

"To say academic expertise should only be on one side is kind of wrong on its face," argues Marc B. Schenker, a professor and chairman of the department of public-health sciences at the University of California at Davis, who led the industry-sponsored semiconductor study. Dr. Schenker, who has consulted with companies and testified on behalf of both plaintiffs and defendants, says scientists need to follow where the data lead, whether or not the findings are politically correct.

The sponsors of the semiconductor study did not interfere with his research, he says. He kept all of the data and was guaranteed the right to publish his results, regardless of how they affected his sponsors' bottom line. His major conclusion was that women who worked in the fabrication room at 14 semiconductor manufacturers had a slightly increased risk of spontaneous abortion.

Unusual Conditions

Other scientists have found Dr. Schenker's study on semiconductor manufacturers convincing. "It was a highly visible study, after much public concern, with an outstanding group of researchers, that got adequate support," says Richard W. Clapp, a professor of environmental health at Boston University, in an e-mail message. "Those conditions are unusual."

Dr. Schenker adds, "I don't see myself as an advocate who manipulates science to reach some preconceived goals." Besides, he says, there would be no reason to bias the results: He makes no money through his corporate-sponsored research studies or his litigation services. Any payment for such work goes to the university, he says.

Patricia A. Buffler, a professor of epidemiology and dean emerita of the School of Public Health at the University of California at Berkeley, is even more insistent that research and industry sponsorship can coexist happily. She has served as an expert witness and consultant -- and been paid for her efforts -- for corporations involved in lawsuits on environmental-health issues.

Ms. Buffler would not tell The Chronicle how much she earns for such work, but she is listed in California Superior Court documents from a continuing case against Lockheed Martin Corporation as an expert witness who has been paid $450 per hour as a consultant for the aerospace company. During the discovery phase of the trial of the case last July, she testified that she had also consulted for Arco, Gulf Oil, Goodyear, Shell Oil, Standard Oil, and Union Carbide, among other companies -- although she says she was not paid for much of that work.

The Lockheed lawsuit, filed in the mid-1990s, pits about 400 residents of Redlands, Calif., against the company. The residents say a Lockheed rocket-testing facility polluted their groundwater and caused cancer and other illnesses. Perchlorate, one of the chemicals that the plaintiffs say they have been exposed to, is known to interfere with thyroid function.

With financial support from Lockheed Martin, Ms. Buffler and other scientists conducted a study that found that area residents did not experience higher risk of thyroid problems than other people did.

The professor says she requires assurance in writing from any company that she agrees to work with that it will not attempt to suppress or manipulate her findings.

"I believe I behave with a very high ethical threshold," she says. "The way to achieve the best public-health goals is to have a strong science base and not to get carried away with poorly based advocacy. That puts me at odds sometimes with the environmental groups, but in the long run that pays off in terms of public health. Shoddy science won't stand up to rigorous scrutiny."

Disappearing Acts

Critics of industry-sponsored research argue that even the most forthright agreements between researcher and industry carry risks of bias in results or interpretation that benefit the sponsors.

"Even under the best of circumstances, there's some understanding that future funding depends at least in part on the results you find this time," says Anthony Robbins, a professor of public health and family medicine at Tufts University, who is a former director of the National Institute for Occupational Safety and Health.

Other critics are more blunt. Daniel T. Teitelbaum, a doctor in Denver who specializes in medical toxicology and occupational epidemiology, says: "Industry doesn't give you money to do research. Industry gives you money to do research that favors them."

When that research doesn't go in industry's favor, critics say, it has a tendency to disappear. "There's a systematic failure to publish positive findings when they happen to conflict with the sponsor's interest," says Sander Greenland, a professor of epidemiology and statistics at the University of California at Los Angeles.

Among the public, in the federal government, and among scientists who test new therapies and drugs, momentum is growing to require listing all clinical trials in a national registry, in order to expose such underreporting. Mr. Greenland argues that the same should be done in epidemiology. But that may be an uphill battle. Some journals in occupational and environmental health do not even require authors to reveal their sources of money or any other potential conflicts of interest.

Aside from the obvious pressures that industry exerts over research, it can influence academic scientists in subtler ways. For example, when companies cast doubt on academic studies, they often force university researchers into long and draining debates that lead to years of additional work, tying up proposed regulations or court cases in endless debates about the validity of the science.

Beate R. Ritz, an associate professor of epidemiology and environmental health at UCLA, has experienced that firsthand.

Because of nearby residents' concerns about their exposure to radiation and to solvents from a facility that tested rockets and nuclear reactors, Dr. Ritz did a study in the mid-90s of the health and employment records of some 55,000 people who had worked at the facility between 1950 and 1993. The facility, which overlooks Simi Valley, had been run by a company called Rocketdyne, which in 1996 became part of the Boeing Company. Dr. Ritz's work was sponsored by the U.S. Department of Energy and cost $750,000.

She and her collaborators found that workers who had had high exposures to radiation were more likely than their colleagues to die of leukemia, and that workers exposed to the rocket fuel hydrazine were at a slightly higher risk of dying of lung cancer.

Residents of neighborhoods near the facility sued Rocketdyne in 1997, concerned that they were at risk for the same cancers. The lawsuits are pending in U.S. district court. Rocketdyne then hired a panel of academic scientists to assess Dr. Ritz's study. When those analyses were completed, her group, as well as Rocketdyne representatives, met with local residents in 1999. The company "said everything we had done was wrong," she recalls. "These people were so antagonistic."

She was taken aback, since her findings had not been scientifically surprising. Her studies had passed peer review and been published in top-flight epidemiology and occupational-medicine journals. But John K. Mitchell, a spokesperson for the company, says, "There were a lot of questions that people felt hadn't been answered by the original study." So Rocketdyne, along with the United Aerospace Workers union, paid a contract research organization $3.5-million to conduct further work.

"They pretty much came up with the same data we had," Dr. Ritz says. "But the way they presented the data made all the effects that are there go away."

Dr. Ritz got another grant from the state of California, for $210,000, to do a follow-up study of her own, which added several more years' worth of deaths to the data. The new study also allowed her to look at the incidence of disease, not just causes of death -- something she had not done earlier because not enough data had yet been entered into California's cancer registry. The later Rocketdyne-commissioned study did not look at incidence either, despite having begun years after Dr. Ritz's study, when more data had become available. "Why didn't they do it?" she asks. "They didn't want to get any results that show something." Mortality data, she says, are less clear-cut and therefore less likely to reveal a causal connection.

Mr. Mitchell denies the charge. He says scientists from the research organization looked at mortality but not illness because "they thought it was more accurate."

Dr. Ritz now has two papers under review on the Rocketdyne case and is writing two more on the new study. As in the original study, she found an increased risk of death from cancer for workers who had been exposed to radiation and to hydrazine.

Other scientists say her experience is not unusual. Researchers feel forced to expand studies or repeat their work after such attacks, says David Ozonoff, a professor of environmental health at Boston University, "to dispel the doubt that industry has created."

In his own research on perchloroethylene, the solvent most often used in dry cleaning -- and a common groundwater contaminant -- he has had to "keep doing studies over and over again" because an industry association keeps casting doubt on his results.

Dr. Robbins, of Tufts, says: "Industry has found it worthwhile to challenge all of the studies that suggest there might be a link between some exposure and some kind of disease or illness ... . Industry is in the business of manufacturing uncertainty."

A Happy Medium

What is the solution? Find a middle ground, say some researchers. An organization cited by many researchers as performing truly independent studies while relying on industry money is the Health Effects Institute.

"They do high-quality work, and it's very transparent," says Mr. Michaels, of George Washington University, who was assistant secretary for environment, safety, and health in the Department of Energy from 1998 to 2001. "They are very careful about doing it right."

The nonprofit institute finances studies and does analyses of existing findings on air pollution and health. It is supported jointly -- and equally -- by the Environmental Protection Agency and a consortium of car-and-truck manufacturers.

Every five years, the institute comes up with a list of research priorities. Based on that, the EPA and the manufacturers provide five-year commitments of money, which currently stand at about $4-million annually. "No matter what we say with any particular study we publish, people can't just pull out," says Daniel S. Greenbaum, the institute's president.

But that example is a lonely one. Like many other scientists, Colin L. Soskolne, a professor of epidemiology at the University of Alberta, in Canada, is distressed by how many other scientists "pursue the interests of vested interests."

"We're all human," he says. "We tend to respond in ways that will ensure that we are secure in our careers. Unfortunately, in my view, this does not always -- perhaps ever -- serve science well or the public interest well."