US: Drug Makers Near Old Goal: A Legal Shield

But because the Food and Drug Administration
approved the patch, the company is arguing in court that it cannot be
sued by women who claim that they were injured by the product - even
though its old label inaccurately described the amount of estrogen it
released.

This legal argument is called pre-emption. After
decades of being dismissed by courts, the tactic now appears to be on
the verge of success, lawyers for plaintiffs and drug companies say.

The
Bush administration has argued strongly in favor of the doctrine, which
holds that the F.D.A. is the only agency with enough expertise to
regulate drug makers and that its decisions should not be
second-guessed by courts. The Supreme Court
is to rule on a case next term that could make pre-emption a legal
standard for drug cases. The court already ruled in February that many
suits against the makers of medical devices like pacemakers are
pre-empted.

More than 3,000 women and their families have sued
Johnson & Johnson, asserting that users of the Ortho Evra patch
suffered heart attacks, strokes and, in 40 cases, death. From 2002 to
2006, the food and drug agency received reports of at least 50 deaths
associated with the drug.

Documents and e-mail messages from
Johnson & Johnson, made public as part of the lawsuits against the
company, show that even before the drug agency approved the product in
2001, the company's own researchers found that the patch delivered far
more estrogen each day than low-dose pills. When it reported the
results publicly, the company reduced the numbers by 40 percent.

The
F.D.A. did not warn the public of the potential risks until November
2005 - six years after the company's own study showed the high estrogen
releases. At that point, the product's label was changed, and prescriptions fell 80 percent, to 187,000 by last February from 900,000 in March 2004.

Gloria Vanderham, a Johnson & Johnson spokeswoman, said the company acted responsibly.

"We
have regularly disclosed data to the F.D.A., the medical community and
the public in a timely manner," Ms. Vanderham said. "Ortho Evra is a
safe and effective birth control option for women when used according
to the labeling."

But Janet Abaray, a plaintiff's lawyer from
Cincinnati, said that Johnson & Johnson took advantage of an agency
overwhelmed by its many responsibilities.

"Johnson & Johnson knew that F.D.A. does not have the funding or the manpower to police drug companies," Ms. Abaray said.

A
series of independent assessments have concluded that the agency is
poorly organized, scientifically deficient and short of money. In
February, its commissioner, Andrew C. von Eschenbach, acknowledged that
the agency faces a crisis and may not be "adequate to regulate the food
and drugs of the 21st century."

The F.D.A. does not test
experimental medicines but relies on drug makers to report the results
of their own tests completely and honestly. Even when companies fail to
follow agency rules, officials rarely seek to penalize them. "These are
scientists, not cops," said David Vladeck, a professor at Georgetown
Law School.

Last month, at a trial over the schizophrenia
drug Zyprexa, Dr. John Gueriguian, a scientist who worked at the F.D.A.
for two decades, testified that the agency did not always ask for
strong warnings even if it believed a drug was risky. Companies
typically oppose warnings, and the agency knows it must compromise on
its requests or face years of delay, Dr. Gueriguian said.

"We at
the F.D.A. know what we can obtain and we cannot obtain," Dr.
Gueriguian said. "We have many, many problems, and we have a management
system - what we can't obtain we will not ask."

For years, top
officials at the agency acknowledged that lawsuits could aid the
agency's oversight of safety issues. In the last decade, suits over
Zyprexa, the withdrawn pain pill Vioxx, the withdrawn diabetes medicine Rezulin, the withdrawn heartburn medicine Propulsid and several antidepressants
have shown that companies played down the risks of their medicines and
failed to disclose clinical trials to the public even as they have
aggressively marketed their drugs.

But now, the agency says a
proliferation of lawsuits could lead to an overlapping patchwork of
rules that would burden companies and might discourage patients from
taking useful medicines.

The Ortho case, however, suggests that
Johnson & Johnson, like other drug makers, is not always quick to
tell the F.D.A. about potential problems with its medicines.

In
1996, the company told the agency it planned to develop the Ortho Evra
patch in part because it would be likely to expose women to less
estrogen than pills. The company suggested that the body would not
break down hormones delivered via the patch as readily as the pill, so
lower doses could be used to achieve contraception. And unlike the pill, which must be taken daily, the patch is changed weekly.

High doses of estrogen are known to raise the risk for blood clots that can cause heart attacks and strokes.

But
a crucial trial completed in 1999 showed that the patch delivered 30 to
38 micrograms of estrogen into the bloodstream each day, according to
company documents.

Because up to half of the estrogen in pills is
lost in the digestive tract before it reaches the blood, the study
suggested that the patch delivered an amount of estrogen that could be
as high as a pill containing 76 micrograms of estrogen. In 1988, the
F.D.A. banned birth control pills with more than 50 micrograms of
estrogen.

But the study's author, Dr. Larry Abrams, who has since
retired from Johnson & Johnson, decided to apply a "correction
factor" to the results of the 1999 trial, according to documents. He
claimed that the patch actually delivered about 40 percent less
estrogen than the trial results showed - about 20 micrograms a day.

Dr.
Abrams made the change, according to his deposition, to adjust for the
different ways the body metabolizes hormones from pills and patches.
This adjustment was never part of the study protocol, a plan filed with
the F.D.A..

"The judgment was made by the pharmacokeneticists at
the time that in doing the calculation, it was probably appropriate to
make that correction," Bob Tucker, a lawyer representing Johnson &
Johnson, said in an interview Thursday. "Later on when people looked at
it in a different time frame, they concluded that probably the
correction shouldn't be applied." The company mentioned its decision to
use the "correction factor" only once in a 435-page report filed with
the F.D.A., and then only in a complex mathematical formula. When the
study was published in 2002, there was no reference to the alteration.

Mr. Tucker said that the F.D.A. was aware of the "correction factor."

Clinical
trials conducted before the patch was approved raised other red flags,
as patients complained of breast soreness and nausea. "The side effects
seem related" to high estrogen doses, one company scientist wrote in an
e-mail message.

Two other studies, one conducted in 1999 and
another in 2003, confirmed that the patch released more estrogen than
the pill. Still, Johnson & Johnson delayed reporting those results
to the food and drug agency, according to documents that have been made
public in lawsuits.

After the patch was approved, the company
marketed it as releasing 20 micrograms of estrogen to the blood every
24 hours, a figure it now acknowledges was inaccurate. It also
acknowledges that the patch releases more estrogen than the pill but
says that the estrogen released under the two methods cannot be
directly compared.

The New York Times provided the drug agency
with a copy of a court brief and asked whether agency medical reviewers
were aware of the "correction factor."

Rita Chappelle, an
F.D.A. spokeswoman, replied, "At present, we are reviewing the
allegations and cannot comment further at this time."

Prescriptions
for the patch grew rapidly after its introduction, reaching more than
900,000 by March 2004, according to data from Wolters Kluwer, a company
that tracks prescription trends. But as the use of the patch rose, so
did reports of side effects.

By 2004, after the death of Zakiya
Kennedy, an 18-year-old college freshman in New York, food and drug
officials had become concerned.

In November 2005, the agency
announced that it had placed a warning that the patch "exposes women to
higher levels of estrogen than most birth control pills."

Since
then, an epidemiological study has shown that women on the patch can
have as much as double the risk of blood clots than those taking pills.
And prescriptions for the patch have fallen 80 percent.

Still,
lawyers for Johnson & Johnson say that patients should not be
allowed to sue the company because the F.D.A. approved the patch and
its label.

"F.D.A. is responsible for making those decisions," said John Winter, a lawyer for the company.

Judge
David A. Katz of Federal District Court for the Northern District of
Ohio is expected to rule soon on whether any of the lawsuits against
Johnson & Johnson can go forward.

In the fall, the Supreme
Court will hear a separate pre-emption case involving Wyeth, another
drug company. Chris Seeger, a plaintiffs' lawyer who has about 125
Ortho Evra cases, said he expected the court to rule in Wyeth's favor.

"Our
lawsuits are the ultimate check against the mistake made by the
government, or fraud made by the companies against the government, or
just an underfunded bureaucracy stretched thin," he said.

• 182 Health
• 208 Regulation