WHY DATA FROM DRUG COMPANIES MAY BE HARD TO SWALLOW BY GUNJAN SINHA
etting drugs on the market means playing games. So says Peter Lurie of Public Citizen, an interest group founded by Ralph Nader
and based in Washington, D.C. Of course, its the agencys mission to be leery. But lately pharmaceutical companies are giving
groups like Luries more to be leery about. Drug firms now wield a great deal of control over their research, Lurie charges,
and they are frequently manipulating their data or withholding unfavorable results entirely.
One of Public Citizens latest battles is over a drug for irritable bowel syndrome (IBS). Three years ago the Food and
Drug Administration approved Lotronex (alosetron hydrochloride), the first agent to treat the disorder specifically.
As published in the Lancet, clinical trials in women revealed that 41 percent taking the drug felt some relief, as
did 29 percent taking a placebo.*
The data, Lurie insists,
"are incredibly misleading. One figure, for example, plots percent change on one axis and time on the other." First, plotting
percent change instead of absolute change makes the effectiveness of the drug appear large. Second, the graph omits data from
the first month, during which the drug and placebo worked almost identically. Public
Citizen reported the data using absolute values. The graph, which the Lancet published in a letter, better represents
the drugs "marginal" efficacy, the group argues.
"I don't understand the
accusation," responds Michael Camilleri of the Mayo Clinic in Rochester, Minn., who led the study. Such presentation
is standard and accepted in peer-reviewed scientific journals. The data clearly show that the drug was better than the placebo
for months two and three.
But many observers believe that drug companies go too far. It shouldn't happen in the scientific literature, insists
Bob Goodman, founder of New York Citybased No Free Lunch, which is focused on reining in the marketing ploys of drug
companies. "Doctors should be able to decide the appropriateness of a drug. But how can they when drug companies leave
out crucial information?" he asks. Goodman is referring to another common practice: excluding data.
Illustrating the point
is the ongoing controversy over Cox-2 inhibitors, touted as a safer alternative to nonsteroidal anti-inflammarories
such as ibuprofen. Sales of one, Celebrex, reached a whopping $3 billion in 2001. But last year the Washington Post revealed
that Pharmacia, the drugs maker, had published just six months of results. Data for the next six months indicated that patients
on Celebrex suffered complications such as stomach ulcers at the same rate as those taking older medications. This information
became public only because one of the paper's reviewers happened to be on the drugs FDA
review committee. Pharmacia says that the data for the last six months were too flawed
to include them.
There are also rumblings
that even though the FDA is aware of such practices, the agency is increasingly acting more favorably toward drug companies.
The Lotronex story again provides the spark for that charge. After the drug hit the market in February 2000, the FDA assigned
Paul D. Stolley of the University of Maryland to review the drugs side-effects profile. Stolley noticed a distressing pattern.
Day after day he would see reports of patients being hospitalized, presumably because of Lotronex. "This for a disease that
never leads to hospitalization, never perforates your colon and is not life-threatening," Stolley points out.
drugs maker, pulled Lotronex off the shelves in November 2000 after 49 reports of ischemic colitis and three deaths. A few
months later, responding in part to requests from IBS advocacy groups, the company appealed to the FDA to bring the drug back. That move alarmed Stolley, who felt that the risks
far outweighed the drugs marginal benefit. But when he spoke up, he was shut out. "FDA
personnel were told not to discuss the case with me," complained Stolley, who had
consulted for the FDA for the past 30 years. Others
were opposed to the drug, but "they were intimidated," says Stolley, who now works for Public Citizen.
Some scientists argue
that the FDA has become so chummy with the
drug industry partly because of the Prescription Drug User Fee Act, passed in 1992. The act requires firms to pay the FDA almost $500,000 in total fees for each approved drug.
Such fees account for almost half the agency's cost of reviewing drugs.
"I was shocked the FDA buckled even after they'd seen the obfuscation and the
attempts to hide data. They seemed more comfortable working with the company than with their own staff," Stolley
grouses. Lotronex is now back on the market. But only authorized doctors can prescribe it, and patients must sign an agreement
staring that they fully understand the hazards. Here's hoping that for them, it is truly a risk worth taking.
Gunjan Sinha is
based in Frankfurt, Germany.
FEBRUARY 2003 Scientific American, P. 15-16.
* There are significant problems with the
placebos used by drug companies, for they can often be identified as sucha topic which I will later publish on.