A Child's Guide to Medical Ethics

Dr. Erdem Cantekin is a thorn in the side of the University of Pittsburgh. From 1976 to 1986, Cantekin was the director of research at the Ear, Nose and Throat Department at the Children's Hospital of Pittsburgh and a member of Dr. Charles Bluestone's research team at the University of Pittsburgh. He now has three lawsuits pending against the university and casually refers to administrators, academics and physicians at the institution as "prostitutes."

The University of Pittsburgh undoubtedly has a few unkind words of its own for Cantekin. He has spent the last seven years bad-mouthing his employers and colleagues. What makes it all the more galling for the university is that Cantekin is still on the payroll. The school can't manage to revoke his tenure since Congress involved itself in an astonishing row that has now been rumbling on for eight years.

The long-running controversy centers on a seemingly straightforward medical issue: How effective is amoxicillin and other antibiotics in the treatment of otitis media with effusion, or "glue ear," an infection of the middle ear that is common in children?

Glue ear is a garden-variety affliction; that's precisely why it is important. In 1990, otitis media (which includes acute infections as well as nonacute glue ear) was the most common diagnosis made by pediatricians in the U.S., responsible for almost 25 million visits to office-based physicians.

According to the Centers of Disease Control, a division of the Public Health Service, antibiotics are prescribed for cases of otitis media more than 95 percent of the time. That represents big business. Each year the pharmaceutical companies sell over $1 billion worth of antibiotics for the condition.

That kind of money has compromised the pursuit of truth at the University of Pittsburgh -- or so Cantekin claims. He maintains that antibiotics do not work against ear infections.

During the 1980s the Otitis Media Research Center (OMRC), part of the University of Pittsburgh, received $18.5 million in grants from the National Institutes of Health -- 40 percent of all federal research funding for otitis media. The grants were given essentially to study the effectiveness of antibiotics in treating the disease. At the same time, Dr. Charles Bluestone and the OMRC received approximately $3.5 million in funding from a number of pharmaceutical companies, including Eli Lilly, Beecham (now merged into SmithKline Beecham), Glaxo and Lederle Labs, all of which manufacture antibiotics used to treat otitis media.

Based on studies between July 1981 and October 1984, Bluestone and his research team concluded that amoxicillin was partly effective in treating glue ear infections. They maintained that after four weeks of treatment it reduced the amount of fluid in the ear. As Bluestone was the head of the University of Pittsburgh's Department of Otolaryngology and a leading authority on otitis media, the integrity of his research would normally go unquestioned.

Enter Cantekin, then a member of Bluestone's research team, and now a self-proclaimed "pariah of the medical-industrial complex." After Cantekin failed to persuade his colleagues of his interpretation of the research data, he accused Bluestone of bias, and of not disclosing to the NIH his funding from the drug companies. "He's in the pockets of the pharmaceutical companies," says Cantekin.

Cantekin's allegations were serious enough to provoke an investigation of the university and later by the NIH.

The director of the NIH's Division of Management Survey and Review concluded that the OMRC had not properly disclosed its funding from pharmaceutical companies. The investigation also revealed that Bluestone had personally received $262,000 over five years in speaking engagement fees, plus annual travel expenses of $25,000, from the companies sponsoring his research.

And after a House Sub-Committee on Human Resources and Inter-governmental Relations hearing on the case in September 1988, the NIH's Office of Research Integrity (ORI), formerly the Office of Scientific Integrity, launched an investigation. Having examined Bluestone's research, the ORI concluded that "these data do not provide support for the long-term effectiveness of any of the antibiotic drugs, relative to placebo, through sixteen weeks."

Bluestone, however, had taken four weeks, as the end point for determining the efficacy of treatment. Even then, the ORI panel had concerns about the study's conclusions. Patients treated with antibiotics were also shown to be as susceptible to recurring infections as those on placebo.

Was Bluestone's interpretation biased by his relationship with the pharmaceutical companies? After all, European studies have concluded that antibiotics are not an effective treatment for glue ear. Furthermore, the widespread use of antibiotics has caused a serious public health problem: drug-resistant bacteria. And many scientists believe overuse of the drugs may be partly responsible for the huge increase in ear infections since 1975.

"I see a knife, I see blood, I see a body on the floor. So I concluded someone has been stabbed," says Leonard Minsky of the National Coalition for Universities in the Public Interest, referring to Bluestone's research. Though Minsky may overstate the evidence at the supposed scene of the crime, there is certainly the appearance of conflict of interest.

The Office of Research Integrity expressed reservations not only about Dr. Bluestone's inadequate disclosure of private funding but about "the less than objective reporting" of research findings. On its recommendations, the OMRC was put on a five-year period of "special oversight" by the NIH. However, it did not find Bluestone guilty of scientific misconduct. The panel also concluded that Cantekin had breached standards of collegiality for scientists, and suggested he be put on faculty oversight for three years. Cantekin is suing the NIH. Bluestone was unavailable for comment. But Lewis Popper, general counsel for the University of Pittsburgh, says the ORI's findings prove there was no merit to the charge of bias on the part of Bluestone.

Meanwhile, the row spread like an infection on Capitol Hill. In its 1990 report, the House Sub-Committee on Government Operations, chaired by the late Representative Ted Weiss, then a democratic congressman from New York, criticized both the University of Pittsburgh and the NIH in its investigations of Cantekin's allegations. Weiss concluded that guidelines at individual institutions were inadequate in dealing with conflicts of interest among federal grantees, and that regulations should be adopted by the NIH.

Can parents be sure that antibiotics will help children suffering from ear infections? Maybe, maybe not.

Because of the divergence of medical opinion on the matter, the Agency on Health Care Policy and Research, a division of the Department of Health and Human Services, convened a panel in November 1991 to devise treatment guidelines for otitis media with effusion. Surprise, surprise: The panel's own objectivity has been questioned by government and medical authorities. Much of the data examined by the panel came from Bluestone's studies and several of the panel members, including the chairman, are from the University of Pittsburgh.

Last fall the first draft of the panel's report was reviewed by outside experts, including Dr. Robert Ruben, chairman of the Department of Otolaryngology at the Albert Einstein College of medicine and the Montefiore Medical Center. Ruben felt that there were serious problems with the panel's conclusions, which supported the use of antibiotics. "The report I saw was a disservice to American children," says Ruben. He asked to see a later draft of the report, but his request was refused.

Finally, just two weeks ago, the panel announced its findings. Do they back up Bluestone? Or do they support Cantekin's view that antibiotics do little except boost the profits of drug companies? Take your choice. The panel says that glue ear often clears up on its own -- surely a strong hint that doctors are wasting huge amounts of money prescribing drugs. It adds that antibiotics "appear to clear up the condition in a small number of children and should be considered as an option ... during the first three months" (our italics). Even then, parents are warned that side effects include diarrhea.

Ruben's misgivings now fall only slightly short of Cantekin's. "It's hard to teach old dogs new tricks. Antibiotics don't help with recurring infection, or pain, or hearing loss, and they have serious side effects. So why use them?"

Whatever the rights and wrongs of the Bluestone affair, there is little doubt that medical research bodies are increasingly reliant upon drug companies to keep their legions of scientists busy.

That poses potential ethical problems that only worsen when individual researchers have a financial stake in the outcome of their work. It is customary practice for federally funded scientists to receive not only extra funding but personal honoraria and fees from pharmaceutical companies whose drugs they are researching.

"Imagine a weapons analyst for the Pentagon being paid by one of the defense contractors. It wouldn't happen," says Danielle Brian, who, as director of the nonprofit Project on Government Oversight, wrote a report on the University of Pittsburgh case. "We assume that scientists are above that level of human incentive."

Arthur Caplan, a professor of bioethics at the University of Pennsylvania, says a financial interest can cause scientists to interpret data more favorably or publish their results too early: "I've seen it happen too many times. Researchers have to be fiscally neutral."

To try to ensure their independence, the NIH proposed guidelines in January 1989. It left specific policies up to universities but identified three key issues to address: researchers' equity holdings in companies with a stake in the outcome of their research; honoraria and fees from companies whose products are being investigated; and the sharing of research results funded with federal money.

Not surprisingly, the guidelines drew criticism from pharmaceutical manufacturers and the medical community. Colleges griped about the administrative burden of disclosure. Drug companies argued that restrictions would obstruct technological innovation. Both groups argued that institutional oversight and peer review are enough to maintain the integrity of privately funded research. The NIH withdrew the guidelines in December 1989. It's now four and a half years and counting, and still no sign of regulation.

But there are signs of a consensus on disclosing paid pipers, whether or not they play the company tune. The NIH is expected to issue rules of disclosure later this year, so at least we may shortly see the baggage that many scientists bring to the research laboratory. But possible regulation of the relationships between physicians and drug companies is where the fur will fly. "The battle will be over what restrictions on stock ownership and financial awards will be put in place," says Caplan.

Don't expect much. The medical profession is a self-governing body, and loathe to give up any ground to the government, especially when it comes to its dealings with the pharmaceutical industry.

Editor's Note: With the appropriate treatment for OME a point of debate, chiropractic research in this area could be the starting point for a conservative movement in pediatric health care.