Pubdate: Tue, 01 Jan 2013
Source: Idaho Statesman, The (ID)
Copyright: 2013 The Idaho Statesman
Contact:  http://www.idahostatesman.com/
Details: http://www.mapinc.org/media/204
Author: Peter Whoriskey, The Washington Post

STUDIES DOWNPLAYED DRUG RISKS

Painkillers Have A Grip On Millions Who Were Told That The Chances Of
Addiction Were Not Great.

PORTSMOUTH, Ohio - The label on OxyContin, which was approved by the
FDA, initially said the risks of addiction were "reported to be small."

The New England Journal of Medicine, the nation's premier medical
publication, informed readers that studies indicated that such
painkillers posed "a minimal risk of addiction."

Another important journal study, which the manufacturer of OxyContin
reprinted 10,000 times, indicated that in a trial of arthritis
patients, only a handful showed withdrawal symptoms.

Those reassuring claims, which became part of a scientific consensus,
have been dropped or called into question in recent years, as many in
the medical profession rediscovered the destructive power of opiates.
But the damage arising from those misconceptions might have been vast.

The nation has been overwhelmed by an ongoing epidemic of addiction to
prescription painkillers - more widespread than cocaine or heroin -
that has left nearly 2 million in its clutches, according to federal
statistics.

"It turns out that the doctors didn't know what they were talking
about," said Barbara Howard, whose daughter, a home-care nurse, died
of an overdose in 2009 in southeast Ohio, an area devastated by the
epidemic. She had developed a habit after knee surgery.

A closer look at the opioid painkiller binge - retail prescriptions
have roughly tripled in the past 20 years - shows that the rising
sales and addictions were catalyzed by a massive effort by
pharmaceutical companies to shape medical opinion and practice.

Opioids are a class of powerful drugs, often used for pain, that
includes morphine, heroin and brand names such as OxyContin, Vicodin
and Percocet.

For years, doctors had been cautious about prescribing opioids to
anyone except patients with cancer or in acute pain.

But drug manufacturers and some pain specialists helped create a body
of scientific research assuaging the long-standing worries about
opioids and pushed to expand the use of the drugs in people with
chronic pain: bad backs, arthritis, sore knees.

Their studies reported minimal risks of addiction and dependence.
These, in turn, were accepted by the FDA and the nation's medical
journals. State medical boards made their rules for prescribing
opioids more liberal. Academic and industry articles dismissed the old
fears as "opiophobia."

These reports reached doctors through marketing efforts and told them
that there were few risks in using opioids to treat chronic pain.

CLOSE TIES

According to a Washington Post examination of key scientific papers, a
court document and FDA records, many of those claims were developed in
studies supported by Purdue Pharma, the maker of OxyContin, or other
drug manufacturers. In addition, the conclusions they reached were
sometimes unsupported by the data, and when the FDA was struggling to
come up with an opioid policy, it turned to a panel populated by
doctors who had financial relationships with Purdue and other drugmakers.

A review of 16 key clinical trials on the subject shows that five were
funded by Purdue and an OxyContin distributor, two were co-authored by
Purdue employees, and two were sponsored by other drug companies
making different opioids. None of the 16 studies showed clear warnings
about the addiction dangers or the physical dependence generated by
the drugs. And the low rate of addiction reported in these studies is
at odds with more recent findings.

Internal company documents indicate that one of the key published
studies sponsored by Purdue - the one reprinted 10,000 times - omitted
suspected cases of withdrawal symptoms. The published paper offered
assurance that only two of more than 100 OxyContin patients had
withdrawal symptoms; the internal documents showed that at least 11
exhibited possible signs of withdrawal, and some experts say it is
likely that at the doses given most of the patients would have
experienced withdrawal.

To refine its policy on opioids, the FDA convened a key meeting in
2002 and invited 10 outside experts for advice. Five of them reported
having served as speakers or investigators for Purdue. Three others
reported working as speakers for or as advisers and consultants to
other pharmaceutical companies.

SECOND THOUGHTS

One of those FDA advisers, Russell Portenoy, who was then the chair of
the Department of Pain Medicine and Palliative Care at the Beth Israel
Medical Center in New York, has since expressed regret for his
evangelism on behalf of opioids.

He was "trying to create a narrative so that the primary care audience
would ... feel more comfortable about opioids," Portenoy said in a
2010 interview with Andrew Kolodny, the chief of a group seeking to
rein in drug use, Physicians for Responsible Opioid Prescribing.
"Because the primary goal was to destigmatize opioids, we often left
evidence behind. ...

"To the extent that some of the adverse outcomes now are as bad as
they have become in terms of endemic occurrences of addiction and
unintentional overdose deaths, it's quite scary to think about how the
growth in that prescribing driven by people like me led in part to
that occurring."

Through a spokesman, Portenoy declined to comment for this report, but
he has said that he continues to believe that many patients with
chronic pain can benefit from opioids.

James Heins, a Purdue spokesman, said that "it is implausible that our
marketing caused an upsurge in overall prescriptions of opioids or in
the incidence of abuse," because the company commands only a small
portion of the painkiller market.

Moreover, he said, the notion that the risk of addiction was small was
"not based on studies funded by Purdue but rather on the larger body
of medical literature and clinical experience."

Even today, he said, it is difficult to say exactly how many people
who are prescribed opioids become addicted.

HITTING HARD

In few places are the effects of the opioid epidemic clearer than in
Portsmouth, a town on the Ohio River near Ohio's borders with West
Virginia and Kentucky. About 10 percent of babies here are born
addicted to opioids. At one point, nine "pill mills" operated out of
this region of 80,000 people. About 20 people a year die of drug
overdoses. And last year, for every resident, more than 100 doses of
opioids were prescribed and dispensed.

Ask someone here whether the risks of opioid addiction are minimal,
and some snort or roll their eyes.

"Around here, we call it 'pharmageddon,' " said Lisa Roberts, the
public health nurse for the town, whose primary job is to reduce the
fatalities associated with drug use. "This has been absolutely
devastating to Appalachia. From what we've seen, the risks of
addiction were tremendous."

Early on in the use of the drug, officials at the Drug Enforcement
Administration perceived the danger to patients.

"The company's aggressive methods, calculated fueling of demand and
the grasp for major market share very much exacerbated OxyContin's
widespread abuse and diversion," a November 2003 memo from the agency
said. "The claim in Purdue's 'educational' video for physicians that
opioid analgesics cause addiction in less than one percent of patients
is not only unsubstantiated but also dangerous because it misleads
prescribers."

AN ABOUT-FACE

The FDA, which must approve drug labels, allowed Purdue to say on its
label: "The development of addiction to opioid analgesics in properly
managed patients with pain has been reported to be rare."

The agency warned that drug abusers and addicts might try to obtain
the drugs, but it indicated that the risks seemed minor for patients:
"We do not know how often patients with continuing (chronic) pain
become addicted to narcotics, but the risk has been reported to be
small."

The agency, however, would later change its mind.

By 2008, the claims that the risks of addiction in patients were small
were removed from the OxyContin label, after "extensive negotiations"
with Purdue, an FDA spokeswoman said.

"The labeling information, including language regarding addiction, has
evolved over time as data has become available," Morgan Liscinsky said.

The FDA did not say what evidence led the agency to allow the previous
claims or what new findings led it to ask for the removal of those
claims. 
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