Healthy Skepticism Library item: 5608

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Berenson A.
Indictment of Doctor Tests Drug Marketing Rules
New York Times 2006 Jul 22
http://www.nytimes.com/2006/07/22/business/22drugdoc.html

Full text:

http://www.nytimes.com/2006/07/22/business/22drugdoc.html

July 22, 2006
Indictment of Doctor Tests Drug Marketing Rules
By ALEX BERENSON

At first, Dr. Peter Gleason thought his arrest was a joke.

In the early afternoon of Monday, March 6, half a dozen men in suits
surrounded Dr. Gleason, a Maryland psychiatrist, at a train station on Long
Island and handcuffed him.

“I said, ‘Well, this is a gag.’ “ Dr. Gleason recalled in a recent
interview. “They said, ‘No, this isn’t.’ “

Dr. Gleason, 53, was taken aback because he was arrested, and later charged,
for doing something that has become common among doctors: promoting a drug
for purposes other than those approved by the federal government.

But prosecutors say that Dr. Gleason went too far. At hundreds of speeches
and seminars where he was rewarded with generous fees, Dr. Gleason advised
other physicians that a powerful drug for narcolepsy could be prescribed for
depression and pain relief. In doing so, he conspired with the drug’s
manufacturer to recommend it for potentially dangerous uses, the prosecutors
claim.

The case has put the spotlight on the murky financial relationships between
drug companies and the physicians they use to promote their medicines.
Companies cannot directly advertise drugs for purposes not approved by the
Food and Drug Administration. But getting drugs prescribed for unapproved
uses can increase a drug’s sales, so companies often skirt the rules by
sponsoring seminars where doctors are paid to make presentations promoting
their drugs, including the “off label” uses.

For doctors, these and other payments they receive for discussing drugs can
be very lucrative. Dr. Gleason acknowledges that he received more than
$100,000 last year alone from Jazz Pharmaceuticals, which makes Xyrem, the
narcolepsy drug he has promoted.

His case could establish limits on what doctors can do to help companies
sell their drugs. But any precedent could be complicated by the history of
Xyrem, which differs in one important way from other drugs. Because the
active ingredient in Xyrem is gamma hydroxybutyrate, or GHB, an illegal
street drug with a history of use in date rape and of overdose hazards,
Xyrem is listed as a federally controlled substance, with distribution
tightly monitored.

Some doctors who have researched Xyrem say that Dr. Gleason, in his
enthusiasm for the drug, may have understated its very real risks. Still, at
least one former F.D.A. official says that the government appears to be
overreaching in going after Dr. Gleason and may chill a common and
legitimate form of medical discussion. “This is a very, very scary
development,” said Daniel E. Troy, a partner at Sidley Austin and the former
chief counsel of the F.D.A.

Dr. Steven Nissen, the interim chairman of cardiovascular medicine at the
Cleveland Clinic, said the case could “have a chilling effect on physicians,
because when we give lectures, we assume that giving an opinion about the
use of a drug is not going to get us into legal difficulty.” The F.D.A. and
federal lawyers, he said, need to restrict criminal prosecutions to
especially egregious cases of off-label promotion.

Continuing to Practice

Dr. Gleason, who is now free on bail and continues to practice medicine,
insists that he is not guilty of conspiracy. He says that he was charged
only after he refused to help the government build a case against the drug’s
maker, Jazz Pharmaceuticals – a sequence of events that court documents seem
to support.

Dr. Gleason freely acknowledges that in meetings with other doctors, he
advocated Xyrem as a treatment for many conditions, including depression and
fibromyalgia, a poorly understood pain disorder.

In a news release about the indictment, an assistant F.B.I. director
compared Dr. Gleason to a “carnival snake-oil salesman.”

But the doctor says that based on his own experience giving Xyrem to
patients, he believes everything he said about the drug and that his right
to express his views are protected by both F.D.A. rules and the First
Amendment.

Some lawyers who have reviewed Dr. Gleason’s case, but are not representing
him, say they agree.

Dr. Gleason has been trapped in the complex rules that cover what doctors
and drug manufacturers are allowed to say about prescription drugs,
according to Harvey A. Silverglate, a lawyer in Boston who specializes in
civil liberties cases.

“What they are doing is criminalizing conduct that is not clearly criminal,”
said Mr. Silverglate, who is not involved in Dr. Gleason’s defense.

Neither the F.D.A. nor the United States attorney’s office in Brooklyn,
which indicted Dr. Gleason, would comment on the case. Nor would David
Loftus, a public defender who has been federally appointed to represent Dr.
Gleason. Jazz Pharmaceuticals, which has not been charged, also declined to
comment.

F.D.A. rules allow doctors to prescribe federally approved drugs for any
purpose, even if it is not indicated on the medicine’s label. But drug
companies are tightly constrained in what they can say about their
medicines. Companies can promote drugs only for their federally approved
purposes – their so-called “on label” use.

“Off label” promotion by drug companies is illegal, and since 2000 drug
makers have paid large fines to settle federal criminal cases over off-label
prescriptions.

Pfizer, for example, paid $430 million in 2004 to settle allegations that it
had promoted Neurontin, an anti-epilepsy medicine, for pain and bipolar
disorder.

Despite the F.D.A.‘s constraints on drug makers, though, the companies are
allowed to hire independent doctors to talk to other physicians about their
medicines. Companies can also sponsor “continuing medical education”
sessions, ranging from lunches to weeklong conferences, where specialist
doctors tell other physicians about the latest developments in their fields – including off-label uses for drugs already on the market. For such
speaking engagements, doctors can receive $3,000 or more a day from the
companies.

In other words, the F.D.A. rules allow drug makers to pay independent
doctors to discuss medicines in ways that might be illegal for the companies
themselves. Beyond the federal rules, guidelines by doctors’ groups give
physicians wide latitude to talk about off-label use.

The American Medical Association considers continuing-education sessions
valuable and believes that doctors should be free to prescribe drugs for
off-label use, according to Dr. Edward Langston, a member of the A.M.A.
board.

In general, though, he said, the A.M.A. believes doctors should rely on
peer-reviewed research, not anecdotal evidence, when they write off-label
prescriptions.

The Accreditation Council for Continuing Medical Education, which oversees
the groups that create medical education sessions, loosened its rules in
2004 so that speakers would not have to disclose whether a recommended use
is on-label or off-label, said Dr. Murray Kopelow, the council’s chief
executive.

“The A.C.C.M.E. abandoned the distinction between off-label and on-label,’‘
Dr. Kopelow said. Instead speakers should make recommendations based on
accepted medical and scientific evidence, he added.

Dr. Gleason acknowledges that he did not follow those evidence-based
guidelines when discussing Xyrem in hundreds of speeches and seminars from
2003 to 2006. The talks were paid for by the original maker of Xyrem, a
company called Orphan Medical. Orphan was acquired by Jazz Pharmaceuticals
in June 2005.

In one seminar cited in the federal indictment, a session last August in
Denver, Dr. Gleason told doctors that “table salt is more dangerous” than
Xyrem – a statement scoffed at by other experts on the drug.

An Aid to Sleep Quality

Xyrem’s active ingredient GHB is a fast-acting central nervous system
depressant developed as an anesthetic in the 1960’s. The drug improves sleep
quality, enabling narcoleptics to stay awake the next day, according to
physicians who specialize in treating sleep disorders. But because GHB can
suppress breathing, overdoses can cause coma or death.

“It has the potential to do a lot of good if it’s used properly, the
potential to do a lot of harm if it’s used improperly,” said Dr. Martin
Scharf, the director of the Tri-State Sleep Disorders Clinic in Cincinnati,
who said he had studied GHB in hundreds of patients since the early 1980’s.

In 2000, after highly publicized cases in which young women died or were
raped after GHB was slipped into their drinks, Congress designated the drug
a Schedule I controlled substance, in the same class as heroin.

But by then, doctors had shown that GHB could treat cataplexy, a variant of
narcolepsy that causes people to suffer temporary paralysis. After lobbying
from doctors and Orphan Medical, Congress said that if the F.D.A. chose to
approve prescription GHB, it would be designated as a Schedule III
controlled substance, legal for medical use, like the painkiller Vicodin or
steroids.

In 2002, after Orphan presented clinical trial data showing GHB’s
effectiveness against cataplexy, the F.D.A. approved the drug, under the
brand name Xyrem, as a cataplexy treatment. In 2005, the agency approved
Xyrem for the treatment of all forms of narcolepsy.

To help persuade the F.D.A. to approve Xyrem, Orphan Medical agreed to make
the drug available only from a single pharmacy in Missouri, which ships it
to patients nationally. No other prescription drug, even other Schedule III
medicines, is so tightly controlled. For now, Xyrem, which costs more than
$600 a month, is a niche product, with sales of about $25 million last year.

Dr. Gleason said he had been interested in Xyrem even before the drug was
officially approved because he believed that other medicines for insomnia
and depression were addictive or had serious side effects. “I immediately
just started prescribing this stuff in 2002,” he said.

He prescribed the drug to about 100 of the patients he saw in his private
practice in Maryland, almost always for off-label conditions like insomnia
and severe depression. Xyrem seemed to work better than existing treatments,
he said.

By early 2003, a sales representative for Orphan Medical, noting Dr.
Gleason’s high rate of prescriptions, asked him if he would give talks to
other doctors about Xyrem.

“I started doing those, and I started getting requested a lot,” Dr. Gleason
said. He received $450 to visit a doctor in the office, $750 for speaking at
a luncheon and $1,500 for a dinner speech. He made as much as $3,000 a day,
he said.

Although he continued to see some patients, the Xyrem talks gradually became
his primary source of income.

In April 2005, after a tip from a whistleblower inside Orphan Medical, the
government began investigating Dr. Gleason and the company, according to an
affidavit that Darren Petri, a criminal investigator for the F.D.A., filed
in February in support of an arrest warrant for Dr. Gleason.

The affidavit says that a cooperating witness repeatedly taped Dr. Gleason
as he discussed Xyrem, including the Denver talk where he compared Xyrem to
table salt and a meeting in November where he said Xyrem was safe for
children.

The indictment also charges that Dr. Gleason committed fraud against
insurance companies by advising doctors to leave blank an area on the Xyrem
prescription form that asked for a disease diagnosis. Dr. Gleason
acknowledges that he told doctors not to offer a diagnosis but says he never
told them to lie if they were asked for one.

Dr. Gleason says he did not know he was under investigation when he went to
Great Neck, N.Y., on March 5 to talk to several doctors about Xyrem during a
lunch meeting at the office of Dr. Richard Blanck, a neurologist. The
meeting had been arranged by a Jazz Pharmaceuticals salesman, Al Caronia,
Dr. Gleason said.

An Unexpected Arrest

Dr. Blanck confirmed the meeting and said Dr. Gleason’s comments seemed
typical for a sales presentation sponsored by a drug company. Mr. Caronia
did not return calls seeking comment.

Afterward, Dr. Gleason says that Mr. Caronia drove him to the Long Island
Rail Road station in the village center, to begin his journey home. When he
stepped out of the car, Dr. Gleason says, Mr. Petri and other investigators
surrounded him, bundled him into a sport utility vehicle and drove him to
the Great Neck police station.

Mr. Caronia was not arrested.

The federal agents said he would have to cooperate in their investigation
into Jazz Pharmaceuticals, Dr. Gleason contends. “They said, ‘Who in this
company roped you into this conspiracy?’ ‘’

Insisting that he had broken no laws, Dr. Gleason said he tried to convince
Mr. Petri and the others that his views on Xyrem were scientifically based.
He was released later that day.

Dr. Gleason’s account is at least partly supported by a letter on March 13
from Geoffrey Kaiser, an assistant United States attorney, to Lois Bloom,
the federal magistrate judge overseeing the case. In the letter, Mr. Kaiser
asks that the case be kept quiet because Mr. Gleason may “be willing to
cooperate with this office in its broader investigation.”

On Bail and Short on Work

The same day, Dr. Gleason was arraigned in Federal District Court in
Brooklyn, where he was released on a $150,000 bond.

It was not until three weeks later, on April 5, that the federal attorney’s
office announced Dr. Gleason’s arrest, with the news release comparing him
to a snake-oil salesman. As he awaits further hearings and trial, Dr.
Gleason, who is divorced, is supporting himself by working as an in-house
doctor on short-term contracts. For a brief period, he worked at a Maryland
state hospital, before being let go. He said the hospital told him he had
been fired because of the indictment; a spokesman for the hospital declined
to comment.

Now he is filling in at various hospitals in Western states, which he did
not want to identify for fear of losing the work.

As for his former benefactor, Jazz, Dr. Gleason says the company told him it
was now cooperating with the investigation and that he would have to face
the indictment on his own.

“They’re just cutting me loose,” he said.

For all that, Dr. Gleason said he still believed in Xyrem. “The only thing
symmetrical with the efficacy and safety of GHB is the hysteria about it.”

Those sorts of claims discomfort even other doctors and researchers who
agree that the drug may be useful.

“He is a very smart man, and I believe he is extremely well intentioned,”
Dr. Scharf said. “But this is not candy. It’s not a cure-all.”