Are drug studies fudged?

Comparison of schizophrenia drugs often favours firm funding study.

Pharmaceutical giant Eli Lilly and Co recently funded five studies in the US that compared its anti-psychotic drug Zyprexa with Risperdal, a competing drug made by Janssen. All five showed Zyprexa was superior in treating schizophrenia.

But when Janssen sponsored its own studies comparing the two drugs, Risperdal came out ahead in three out of four.

In fact, when psychiatrist John Davis analysed every publicly available trial funded by the pharmaceutical industry pitting five new anti-psychotic drugs against one another, nine in 10 showed that the best drug was the one made by the company funding the study.

"On the basis of these contrasting findings in head-to-head trials, it appears that whichever company sponsors the trial produces the better anti-psychotic drug," Davis and others wrote in the American Journal of Psychiatry.

Such studies make up the bulk of the evidence that American doctors rely on to prescribe $10 billion worth of anti-psychotic medications each year. Davis pointed out the potential biases in design and interpretation that produced such contradictory results. Other experts note that industry studies invariably seek to boost the image of expensive drugs that are still under patent. Moreover, they say, the trials are relatively brief and test drugs on patients with simpler problems than doctors typically encounter in daily practice.

By contrast, when the federal government recently compared a broader range of drugs in typical schizophrenia patients in a lengthy trial, two medications that stood out were cheaper drugs not under patent. The medication that worked best for patients with severe, intractable schizophrenia was clozapine, whose sales lag well behind every other drug in its class. And an earlier leg of the study found that the largely unused drug perphenazine had about the same risks and benefits as far more expensive competitors that are widely assumed to be safer.

Exacerbated

Reliance on industry-sponsored studies is not limited to psychiatry, but experts say the problem is exacerbated in areas of medicine where the goal of trials is not to demonstrate cures but to measure symptomatic relief, which allows more latitude in how the results are interpreted and marketed. Now a growing chorus of experts is asking whether the research establishment needs to be reoriented toward publicly-funded studies that might better guide clinical decisions and the billions of tax dollars the government itself spends on treatment.

"A perfectly independent agency has to be set up that says, ?Here are the areas where trials must be done'," said Drummond Rennie, deputy editor of the Journal of the American Medical Association. "There will be two classes of trials - the believable ones and the non-believable ones."

The problem is not that companies fabricate results, experts say. Researchers, in fact, want drugmakers to sponsor more studies, not fewer. But ostensibly valid industry studies can be misleading in multiple ways, Davis said. Some use too low a dose of a competitor's drug, while others choose statistical techniques that show their drug in the best light. Virtually all test drugs on patients with relatively straightforward problems.

Davis warned that the circular results he found could undermine the confidence of clinicians and patients, and even cast doubt on medications that are genuinely superior. He and Rennie also questioned academic researchers' role in these studies.

Davis, who joked in an interview that he no longer gets to fly first class to Tokyo and Monte Carlo since he stopped accepting money from pharmaceutical companies, guessed that 90 per cent of industry-sponsored studies that boast a prominent academic as the lead author are conducted by a company that later enlists a university researcher as the "author".

"We know that happens all the time," Rennie said. "The only reason that the company wants a non-company person as an author is to give credence to an advertisement. ... The whole paper from start to finish is an advertisement. It is a much more subtle and telling ad than anything they can publish as an ad."

Drugmakers defend their studies, and Davis emphasised that the drugs do help patients. But doctors, he said, cannot afford to take the results at face value.

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 anti-psychotic 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 judgement and experience of the clinician in selecting among a fortunately broad palette of medicines."