2004-06-07-WP-Drugmakers Prefer Silence On Test Data

July 6, 2004

http://www.washingtonpost.com/wp-dyn/articles/A29576-2004Jul5.html

http://www.washingtonpost.com/wp-dyn/articles/A29576-2004Jul5_2.html

Drugmakers Prefer Silence On Test Data

Firms Violate U.S. Law By Not Registering Trials

By Shankar Vedantam

Washington Post Staff Writer

Tuesday, July 6, 2004; Page A01

The pharmaceutical industry has repeatedly violated federal law by

failing to disclose the existence of large numbers of its clinical

trials to a government database, according to the Food and Drug

Administration.

Doctors and patients say that compliance with the law would go a long

way toward addressing their growing concerns that they are not being

given the full picture about the effectiveness of many drugs because

they are not told about drug trials that fail. The issue has gained

urgency with recent disclosures that the publicly available research

on treating children with antidepressants obscured the fact that in

most studies, the drugs were no better than sugar pills. Drugmakers

chose not to publish those studies.

The 1997 law is so little known that scientific journal editors and

professional medical associations have recently debated whether to

create a system of private incentives for disclosure of trials. When

she was told the law already requires companies to register trials,

DeAngelis, editor in chief of the Journal of the American

Medical Association, said, " That's a surprise to me. Tell me why it's

not enforced. "

Although the law was primarily passed for other reasons, DeAngelis

said it could very well address her concerns.

The FDA acknowledges it has not enforced the law -- officials said

the statute did not spell out penalties or explicitly give the agency

authority to crack down on violators.

An FDA analysis found that in 2002 only 48 percent of trials of

cancer drugs had been registered, and a preliminary review now

indicates the listing rate for drugs for some other serious diseases

is in the single digits. Some companies have listed no studies; some

trials are listed without identifying the sponsoring company or the

drug being tested.

As of Friday, the database, ClinicalTrials.gov, listed 5,754 ongoing

studies, but only 13 percent were industry sponsored. The federal

government, mainly the National Institutes of Health, accounted for

55 percent. Those proportions are in stark contrast to the true

picture, DeAngelis said. " Over 80 percent of trials are funded by for-

profit companies, not by the government, " she said.

FDA officials said they are re-examining whether they have the power

to step in. Members of Congress are also considering adding

enforcement provisions to the law, which was part of the FDA

Modernization Act of 1997.

The registry was begun in 1998 and the ClinicalTrials.gov site went

online in February 2000, said a McCray, director of biomedical

communications at the National Library of Medicine, which hosts the

registry. Since then, nearly 11,000 trials have been registered from

all 50 states and 90 countries. Virtually all studies sponsored by

the National Institutes of Health are listed, and industry trials

started coming in after March 2002, when the FDA issued a

formal " guidance " on implementing the law.

Although some companies say they are amenable to wider disclosure,

the patient advocacy group that fought the hardest to create the

requirement predicted it would never be enforced.

(part 2)

" Obviously it needs an enforcement mechanism attached to it, " said

Abbey S. Meyers, president of the National Organization for Rare

Disorders. " I can guarantee you, however, that the full force of the

drug industry will stop it. They don't want you to know about

clinical trials that fail. They are afraid what it will do to their

stock price. A lot of trials are for drugs already on the market, and

it would ruin their sales if the news got out. "

The Pharmaceutical Research and Manufacturers of America countered

that the registry had initially been slow to list industry-sponsored

trials, and that companies started supplying the information after

the FDA issued its guidance. Alan Goldhammer, PhRMA's associate vice

president for regulatory affairs, said he had heard anecdotally that

companies are now fully complying with the law.

But Theresa Toigo, director of the FDA's Office of Special Health

Issues, painted a different picture. " Many pharmaceutical trials are

not participating in ClinicalTrials.gov or are not fully

participating, " she wrote in a recent report in the Journal of Biolaw

and Business. Responding to assertions by PhRMA that the 2002 data do

not reflect the current situation, she said, " It's not like we've

seen a big increase in the monthly submissions of privately sponsored

protocols. "

Sen. M. Kennedy (D-Mass.), who helped create the registry in

1997, plans to seek revisions to enforce the registration requirement

and to find a way to report study results.

Meyers and Kim, a former Kennedy staff member who now works for

the law firm Foley Hoag LLP, said the original purpose of the

registry was to link patients who wanted to join clinical trials with

the researchers.

The law required companies to register all effectiveness trials,

known as Phase 2, 3 or 4 studies, for serious and life-threatening

diseases. In 2002 , the FDA defined " serious " diseases broadly,

including everything from AIDS and cancer to arthritis, depression

and diabetes.

Some companies have boasted to stockholders of having many ongoing

studies in the pipeline but not listed any with the registry. Forest

Laboratories Inc., which recently touted results for an Alzheimer's

disease drug called memantine and last month published a children's

depression study showing positive results for its antidepressant

Celexa, has no trials registered. Company spokesman Triano

said the law does not require companies to register trials if other

drugs are available for the same disease.

Triano said the company did not need to list its trials of memantine,

a new class of Alzheimer's drug, because the FDA had not given it

the " fast-track " status reserved for breakthrough medicines and

deadly diseases with limited treatments.

The FDA's Toigo said the law required companies to register trials

whether or not medicines exist for the disease. " It doesn't say

anything about existing drugs on the market, " she said.

Although 246 pharmaceutical and biotech companies had ongoing trials

in the database Friday, about half listed just one. GlaxoKline

had five, but spokesman Rick Koenig said many of the company's trials

are not listed under the company's name. " We didn't understand that

to be a requirement or the sort of information that is of use to a

patient looking into where that patient might enroll in a trial, " he

said.

Toigo said the FDA's 2002 guidelines called for companies to include

their names.

Journal editor DeAngelis, who is helping spearhead an editors'

initiative to get all trials registered, said a government-enforced

registry would be vastly superior to any system of private

incentives. " It will come as a surprise to the vast majority of your

readers, " she said about the law's requirements. " I had personally

assumed it was only for federally funded clinical trials. "

Toigo said her analysis of industry compliance, which she hopes to

complete by the end of the year, will examine whether more than 2,000

trials submitted to the FDA by companies seeking approval for

medicines in 2002 had been properly listed.

Companies are hesitant to register trials because they want to

control data, said Kay Dickersin, a professor at Brown University who

has sought such data for two decades. Some are worried that trade

secrets will leak out, or that a competitor will poach on patient

networks. Others don't want patients to petition them for medicines

on " compassionate grounds. "

One way to increase registration, said Dickersin, is for patients to

insist trials be registered before participating. Drummond Rennie, a

professor at the University of California in San Francisco, added

that physicians who conduct trials for companies " should examine

their consciences " before agreeing to let trials be kept secret.

" If I buy a camera and the thing falls apart, it's a lemon, I shrug

and say I'm never going back to that firm, " said Rennie, who is also

deputy editor at JAMA. " But if I get a drug and it makes me worse, it

can kill me or maim me.

" We give pharmaceutical companies a lot of tax advantages and a whole

lot of support in the Congress and a good business environment and

patent protection, " he said. " They owe us more information. "

July 6, 2004