Comparison of Schizophrenia Drugs Often Favors Firm Funding Study

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Sara Corya, medical director for neuroscience at Eli Lilly, a company Davis singled out for praise for the quality of its studies, said that conflicting results do not cancel each other out, and that they help clinicians understand the strengths of different drugs. Corya and Davis noted that Lilly has strict rules to prevent author-shopping.

"The reality is that even in head-to-head comparisons, study results will differ for a variety of reasons, some transparent, some opaque," added Mariann Caprino, a spokeswoman for Pfizer, whose antipsychotic drug Geodon did not perform as well as Zyprexa in two trials funded by Eli Lilly. Pfizer's own studies found that Geodon was superior to Zyprexa in one trial and inferior in another.

"What this all means," Caprino said, "is there is no substitute for the judgment and experience of the clinician in selecting among a fortunately broad palette of medicines."

But several experts say industry-sponsored trials are failing to answer the questions doctors really need answered: Which drug works best for which patient? Are differences in drugs worth the differences in cost? How many patients are likely to recover entirely, rather than just show progress in the right direction? Head-to-head trials of similar medications may show statistical differences in how they perform, but those differences may not mean very much for doctors and patients, said Robert Rosenheck, a Yale psychiatrist.

What a clinician wants to know is whether the patient she is treating will get better on a drug, said Thomas R. Insel, director of the National Institute of Mental Health. "If they are not going to get well, what is the better approach? The public is less interested in statistical significance and more interested in clinical significance."

The difference between the two was highlighted by the recent study of antipsychotic drugs funded by the National Institute of Mental Health. Rather than focus on how some symptom or side effect waxes and wanes, the government trial focused on the big picture: How do typical schizophrenia patients fare on the drugs over the long term?

The results were sobering: Regardless of the drug, three-quarters of all patients stopped taking it, either because it did not make them better or had intolerable side effects. The discontinuation rates remained high when they were switched to a new drug, but patients stayed on clozapine about 11 months, compared with only three months for Seroquel, Risperdal or Zyprexa, which are far more heavily marketed -- and dominate sales.

"Clozapine is better by far than the other antipsychotics," said Carol Tamminga, a psychiatry professor at the University of Texas Southwestern Medical Center at Dallas, who wrote an editorial in the American Journal of Psychiatry about the trial. "The question is: Why do doctors not use it?"

The drug requires more careful monitoring to prevent potentially fatal bone-marrow toxicity, she said, but a national monitoring program ensures it is used properly. Tamminga agreed that marketing may play a role in why the drug is not used more often.

"Clozapine is less marketed," she said. "It is off patent. Even when it was on patent, it has never been as actively marketed as the other drugs."

The government study also provided the big picture missing from company-sponsored trials, said Jeffrey Lieberman, a Columbia University psychiatrist who led the first phase of the study: "The drugs work, but only so well. They are not meeting expectations."

By focusing on the horse race -- which drug is marginally better -- industry studies obscure the reality that better drugs are needed overall, agreed Rennie, who is a professor of medicine at the University of California at San Francisco.

"Finding the 100th similar antipsychotic drug is not where the research should be," he said. "It should be to develop new drugs, not 'me, too' drugs."

Rennie said that government agencies such as the Centers for Medicaid and Medicare Services and the Department of Veterans Affairs that disburse billions of dollars for treatment should rely on publicly funded studies.

"There are lots of questions that drug companies are not going to be primarily interested in," agreed Robert Temple, a senior official at the Food and Drug Administration. He has long been a personal advocate of what he calls a "national problems laboratory."

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But Uwe Reinhardt, a political economist at Princeton, said drug companies, device manufacturers and even physicians are reluctant to delve into questions of cost-effectiveness because such inquiries may find that the latest, most expensive treatment is not worth the cost.

"I have come to believe a lot of inefficiency is quite deliberate and supported by Congress," he said. "One person's inefficiency is another person's income."

Source: Washington Post

Last updated: 3/06

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