9 Out of 10 Company Drug Trials Biased_WashPost

April 13, 2006

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Which psychotropic drug is best? " it appears that whichever company

sponsors the trial produces the better antipsychotic drug. "

That acknowledgement was made by Dr. , a prominent

psychiatrist, an endowed professor at the University of Illinois,

Chilcago, whose review of antipsychotics reveals that 9 out 10

industry-sponsored journal reports are fraudulent.

Indeed, leading schizophrenia drug researchers--and psychiatry's

premier publications are unable to continue pretending that

psychiatry's clinical practice guidelines are based on anything

remotely resembling scientific evidence. Practice guidelines in

psychiatry are based on biased trials and fraudulent claims.

The incontrovertible findings that have forced leading schizophrenia

researchers to acknowledge is that the most widely prescribed, most

exspensive atypical antipsychotics that they have recommended as

first line treatment for over a decade, lack clinical efficacy and

produce adverse side effects whose magnitude is " staggering, " .

The Washington Post reports, " 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. "

Dr. Drummond Rennie, Deputy editor of the Journal of the American

Medical Association (JAMA), puts it this way: " The only reason that

the company wants a non-company person as an author is to give

credence to an advertisement. . . . The whole entire 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. "

In other word, journals such as AJP, JAMA, The Lancet, The New

England Journal of Medicine, not to mention psychiatry's journals,

including the Archives of General Psychiatry, Biological Psychiatry,

J of the Academy of Child & Adolescent Psychiatry…etc., have ALL

lent their pages to advertisements disguised as " peer reviewed "

scientific reports!

This is evidence of fraud.

The problem is that fraud in the scientific literature is

not 'merely' academic: beyond polluting the integrity of the

scientific literature with advertisements that are then cited as if

they were scientific resports, but these fraudulent reports have

caused irreperable harm to patients. As Shankar Vedantam points out

in the Post,

" Such studies make up the bulk of the evidence that American doctors

rely on to prescribe $10 billion worth of antipsychotic medications

each year. pointed out the potential biases in design and

interpretation that produced such contradictory results. "

Indeed, as now acknowledged for the first time by a leading

schizophrnia researcher, Dr. Carol Tamminga, the adverse side effect

outcomes of antipsychotics " are staggering in their magnitude and

extent and demonstrate the significant medication burden for persons

with schizophrenia.… Sky-high drug discontinuation rates were seen,

suggesting rampant drug dissatisfaction and inefficacy. "

We do not believe that a new agency, as Dr. Rennie recommends, is the

medicine that's needed to protect the integrity of science. Such an

agency will most likely be subject to politics, or it will be

stacked--as are most government and academic advisory panels alike.

FDA advisory committees as well as EPA, NIH, DHHS, and, IOM have been

plagued by conflicts of interest in favor of industry.

The peer review process itself must undergo a major overhaul so that

nothing less than absolute transparency emerges. Only when the

reviewing process at the journals is subject to independent review--

including reviewers who have no conflicts of interest--and those who

do, fully disclose such conflicts. All reviews of reports that are

published in scientific journals--whether these are favorable or

unfavorable--should be made visible for public examination.

Similalrly, the raw data from clinical trials should also be made

accessible for independent review.

Only when the process is open and above board can one speak of

transparency; only then will the integrity of medical research be

restored.

Contact: Vera Hassner Sharav

212-595-8974

veracare@...

Comparison of Schizophrenia Drugs Often Favors Firm Funding Study

By Shankar Vedantam

Washington Post Staff Writer

Wednesday, April 12, 2006; A01

Pharmaceutical giant Eli Lilly and Co. recently funded five studies

that compared its antipsychotic 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 analyzed every publicly

available trial funded by the pharmaceutical industry pitting five

new antipsychotic 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 antipsychotic drug, " 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 antipsychotic medications

each year. 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.

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, 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.

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.

, 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 percent 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 entire 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 emphasized 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

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 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 nn 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 Rosenheck, a Yale

psychiatrist.

What a clinician wants to know is whether the patient she is treating

will get better on a drug, said 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 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 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. "

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. "

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April 13, 2006