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.*
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.
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.
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.
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
the 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.
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
Sinha is based in Frankfurt, Germany.
FEBRUARY 2003 Scientific American, P. 15-16.