The New York Times reports (below) that additional state Attorneys General are demanding that Eli "Lilly hand over marketing materials, e-mail messages, and other documents with information about promotion of Zyprexa."

Illinois and Vermont are the latest states to hit Lilly with the civil
equivalents of criminal subpoenas. California, Florida, Pennsylvania have
already begun investigating.

The Times suggests that criminal prosecution would be difficult: "as long as
drug makers comply with federal requirements to provide data about their
products to the Food and Drug Administration, companies have a relatively
strong defense against criminal prosecution."

The question is: what "data about their products" did Lilly submit to the
FDA? Did the company provided the FDA with ALL of its safety / efficacy /
marketing data ?

If so, then FDA officials who remained mute as the drug undermined the
physical health of those for whom it was prescribed off-label, are equally
culpable.  It is doubtful, however, that Lilly submitted ALL evidence to the
FDA.

Forbes reports about the off-label use of antipsychotics, noting that Dr.
David Atkins, chief medical officer of the Agency for Healthcare Research
and Quality (AHRQ) Center for Outcomes and Evidence,  acknowledged: "The
issue of off-label indications is a problem across medications, but I think
it's particularly of concern with drugs that affect mental-health issues."

A review of 84 published studies on atypical antipsychotics–which do not
include failed studies that the manufacturers conceal–the authors of the
new study concluded that there can be problems. "Not only is quality
evidence lacking to support off-label use of the drugs, there is evidence of
severe side effects, including weight gain, tremors and stroke."

The report comes on the heels of another study that found that antipsychotic
drugs, commonly prescribed to treat psychosis, agitation and aggression in
Alzheimer's patients, are essentially no more effective than a sugar pill.

Indeed,  the overwhelming evidence from independent government funded
outcome studies–such as CATIE–confirms that current psychotropic drug
prescribing practices–by psychiatrists, primary care physicians, and
pediatricians alike–lack medical-scientific justification.

The evidence shows that the second generation neuroleptics (a.k.a. 'atypical
antipsychotics') pose an alarmingly unfavorable risk / benefit ratio. 

The recent stream of public revelations have jolted even staunch defenders
of psychotropic drugs–as for example, Jeffrey Lieberman, MD. Chairman of
psychiatry, Columbia University, Carol Tamminga, MD. Professor, Southwestern
Medical School, Texas.

Forbes quotes  Dr. Julio Licinio, chairman of psychiatry and behavioral
sciences at the University of Miami Miller School of Medicine: "The surprise
is that people have not been more adamant about this earlier….These drugs
have a lot of side effects.They also tend to be very expensive."  He went on
to say, "It's not only that people are getting anti-psychotics, they are
being added to what they are already taking. They are being added, and they
have not been tested in combinations, and I think it's a problem."

The study authors make the predictable academic recommendation calling for
more studies… That "safe" recommendation is rejected by Dr. Cheryl Corcoran, of  Columbia
University and the New York State Psychiatric Institute in New York City.
Dr. Corcoran clearly has the welfare of test subjects in mind when she notes
that although "there are very few clinical trials in children, [sic] there's
enough information from other sources to show that these medications can be
very problematic for children, with side effects such as weight gain,
insulin resistance and changes in cholesterol."

"Our sense is not more head-to-head trials but the need to develop other
kinds of treatments for disorders other than psychosis, drugs that are
safer, more appropriate, using rationale drug design," she said.

Contact: Vera Hassner Sharav
veracare@ahrp.org
 
http://www.nytimes.com/2007/01/20/business/20drug.html
THE NEW YORK TIMES
January 20, 2007 C-1
States Study Marketing of Lilly Pill
By ALEX BERENSON

Stepping up government investigations into Eli Lilly's marketing of its
best-selling drug Zyprexa, state prosecutors in Illinois and Vermont have
demanded that the company turn over information about the way it promoted
the medication.

On Thursday, lawyers from the consumer protection division of the Illinois
attorney general's office demanded that Lilly hand over marketing materials,
e-mail messages, and other documents with information about promotion of
Zyprexa. Vermont investigators issued a similar order yesterday morning.

The orders are the civil equivalents of criminal subpoenas, according to
Deborah Hagan, the chief of the Illinois consumer protection division.

Illinois and Vermont are now part of a coordinated five-state civil
investigation into the way Lilly promoted Zyprexa, a treatment for
schizophrenia and bipolar disorder. The states are investigating whether
Lilly tried to hide Zyprexa's risk of causing weight gain and other risks
associated with diabetes and whether the company promoted Zyprexa for use in
patients who do not have schizophrenia or bipolar disorder.

Federal laws prohibit such so-called "off label" marketing, although doctors
may prescribe any drug for any disease that they believe the drug will help.

The orders on Thursday and yesterday are the first formal demands for Lilly
documents from state attorneys and they indicate an escalation of the
investigation, according to Ms. Hagan and Julie Brill, who is an assistant
attorney general in Vermont.

"We can ask for documents; we can ask for answers to questions; and we can
ask for people to come in and testify under oath," Ms. Hagan said. Federal
prosecutors in Philadelphia have also recently accelerated their own
investigation into Lilly's marketing of Zyprexa.

In a statement yesterday, Lilly said it would cooperate with the
investigations and had done nothing wrong. "We intend to cooperate with the
Illinois attorney general's civil investigative demand relating to Zyprexa,"
the company said. "We cannot comment further about this or other ongoing
investigations."

While the investigation being led by Illinois is civil, other investigations
into Lilly's conduct are both civil and criminal. Attorneys general in
California and Florida may seek to recover Medicaid payments that the states
made for Zyprexa. Medicaid represents a sizable percentage of the drug's
overall sales because many people who take the medicine are disabled and do
not work.

Any fine or cost recovery could be sizable, because Zyprexa has been a
commercial success. The drug is by far Eli Lilly's largest-selling product,
with sales of $4.2 billion last year and about $30 billion since its
introduction in 1996. More than 20 million people have taken Zyprexa since
Lilly began selling the drug.

The investigations could continue for months or possibly years, people
involved in the cases say, as investigators sift through tens of thousands
of documents from the company and talk to current and former employees.

Zyprexa, whose generic name is olanzapine, is a potent chemical that binds
with receptors in the brain to reduce the symptoms of schizophrenia and
bipolar disorder. But Zyprexa also causes severe weight gain and changes in
blood sugar and cholesterol in many patients who take it.

Internal Lilly documents provided to The New York Times last month by a
lawyer in Alaska who represents people with mental illness indicate that
Lilly has engaged in a decade-long campaign to play down the seriousness of
the side effects of Zyprexa.

Lilly did not disclose to doctors that its own data showed that 16 percent
of people taking Zyprexa for a year gained more than 66 pounds, according to
the documents.

The documents also indicate that the company told its drug representatives
to promote Zyprexa to doctors for the treatment of conditions other than
bipolar disorder or schizophrenia.

Lilly has said it did not market Zyprexa off-label and said so again in its
statement yesterday.

"Lilly is committed to the highest ethical standards and to promoting our
medications only for approved uses," the company said.

But its marketing materials have repeated references to promoting the drug
for other uses. And some sales representatives and doctors have also said
they believed that the company was marketing off-label.

Still, any criminal prosecution of the company could face a high burden.
While settlements of off-label marketing cases have led to large fines, such
cases so far have fizzled if they reach juries.

And as long as drug makers comply with federal requirements to provide data
about their products to the Food and Drug Administration, companies have a
relatively strong defense against criminal prosecution, according to lawyers
who are experts in drug marketing.

Copyright 2007 The New York Times Company
~~~~~~~~~

http://www.forbes.com/forbeslife/health/feeds/hscout/2007/01/19/hscout601162.html
FORBES
Study Questions 'Off-Label' Use of Antipsychotics
01.19.07, 12:00 AM ET FRIDAY, Jan. 19

(HealthDay News) — Newer antipsychotic medications are being used widely
for a variety of psychiatric disorders for which they were not initially
approved.
This "off label" use comes without strong evidence that the drugs are
effective for these conditions and with a risk for serious side effects,
said a report issued this week by the Agency for Healthcare Research and
Quality (AHRQ).

The medications were approved to treat conditions such as schizophrenia and
bipolar disorder, but are now being prescribed to millions of Americans for
depression, dementia, and other psychiatric disorders without strong
evidence that such off-label uses are effective, the report stated.

"The issue of off-label indications is a problem across medications, but I
think it's particularly of concern with drugs that affect mental-health
issues," said Dr. David Atkins, chief medical officer at AHRQ's Center for
Outcomes and Evidence.

The revelation, contained in an AHRQ report titled Efficacy and Comparative
Effectiveness of Off-Label Use of Atypical Antipsychotics, was not startling
to clinicians.

"The surprise is that people have not been more adamant about this earlier,"
said Dr. Julio Licinio, chairman of psychiatry and behavioral sciences at
the University of Miami Miller School of Medicine.

The report comes on the heels of another study that found that antipsychotic
drugs, commonly prescribed to treat psychosis, agitation and aggression in
Alzheimer's patients, are essentially no more effective than a sugar pill.

Atypical antipsychotics such as aripiprazole (Abilify), olanzapine
(Zyprexa), quetiapine (Seroquel), risperidone (Risperdal) and ziprasidone
(Geodon) are designed to cause fewer neurological complications than older
antipsychotics. They are approved to treat schizophrenia and bipolar
disorder but are increasingly used to treat dementia, geriatric aggression,
depression, obsessive-compulsive disorder, post-traumatic stress disorder
and personality disorders.

Using the drugs "off label' for conditions other than their original
approval is perfectly legal but causes concern among some experts. A 2001
report by the AHRQ concluded that about 21 percent of prescribed drug use
was for conditions not indicated on the label.

Atypical antipsychotics have also been studied for treating Tourette
syndrome and autism in children.

"Off-label use isn't necessarily bad," Atkins said. "To say it's not an
approved indication doesn't mean there's no evidence."

But after reviewing 84 published studies on atypical antipsychotics, the
authors of the new study concluded there can be problems. Not only is
quality evidence lacking to support off-label use of the drugs, there is
evidence of severe side effects, including weight gain, tremors and stroke.

"These drugs have a lot of side effects," Licinio confirmed. "They also tend
to be very expensive."

Although some patients can benefit from the off-label use, many can be
treated with a different drug without the side effects, he added.

The drugs are also used widely in children for off-label purposes, said Dr.
Cheryl Corcoran, assistant professor of psychiatry at Columbia University
and a researcher in schizophrenia at the New York State Psychiatric
Institute in New York City.  "There are very few clinical trials in
children, but there's enough information from other sources to show that
these medications can be very problematic for children, with side effects
such as weight gain, insulin resistance and changes in cholesterol," she
said.

Licinio added there are few studies that looked at the drugs in "real-world"
settings, which often means in combination with other drugs. "It's not only
that people are getting anti-psychotics, they are being added to what they
are already taking," he said. "They are being added, and they have not been
tested in combinations, and I think it's a problem."

The study authors called for more head-to-head trials of the drugs. "The
clearest finding was that the quality of evidence for the most common uses
was not very clear-cut, which doesn't prove the case that these aren't
appropriate to consider in individual patients. But it does say that given
the amount of use they're getting, we need some better research to try to
clarify how to identify the right patients to get these drugs," Atkins said.

But Corcoran and others called for a different approach.  "Our sense is not
more head-to-head trials but the need to develop other kinds of treatments
for disorders other than psychosis, drugs that are safer, more appropriate,
using rationale drug design," she said.

 ~~~~  
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