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In Documents on Pain Drug,
Signs of Doubt and Deception
By Katie Thomas, The New York
Times
June 24, 2012
Picture Credit:
Michael McElroy for The New York Times
Dr. Steven
Nissen is overseeing a trial on Celebrex that
is scheduled for completion in 2014, the year
the drug’s patent expires. He dismisses any
claim that Pfizer has delayed the study.
A
research director for Pfizer was positively buoyant
after reading that an important medical conference had
just featured a study claiming that the new arthritis
drug Celebrex was safer on the stomach than more
established drugs.
“They swallowed our
story, hook, line and sinker,” he wrote in an e-mail
to a colleague.
The truth was that Celebrex was no better at
protecting the stomach from serious complications than
other drugs. It appeared that way only because Pfizer
and its partner, Pharmacia, presented the results from
the first six months of a yearlong study rather than
the whole thing.
The companies had a lot riding on the outcome of the
study, given that Celebrex’s effect on the stomach was
its principal selling point. Earlier studies had shown
it was no better at relieving pain than common drugs —
like ibuprofen — already on the market.
The research chief’s e-mail, sent in 2000, is among
thousands of pages of internal documents and
depositions unsealed recently by a federal judge in a
long-running securities fraud case against Pfizer.
While the companies’ handling of the research was
revealed a dozen years ago, the documents provide a
vivid picture of the calculation made by Pfizer at the
time and its efforts ever since to overcome doubts
about the drug.
The documents suggest that officials made a strategic
decision during the early trial to be less than
forthcoming about the drug’s safety. They show that
executives considered attacking the trial’s design
before they even knew the results and disregarded the
advice of an employee and an outside consultant who
had argued the companies should disclose the fact that
they were using incomplete data.
In one e-mail, an associate medical director at
Pharmacia (which was later bought by Pfizer)
disparaged the way the study was being presented as
“data massage,” for “no other reason than it happens
to look better.”
In another, a medical director at Pfizer described it
as “cherry-picking the data” even as officials were
publicly boasting of the study’s success. Dr. M.
Michael Wolfe, a gastroenterologist who had cautiously
praised the study in a medical journal at the outset,
said after reviewing the new documents: “I always try
to give investigators the benefit of the doubt, but
these communications make it quite challenging for
me.”
The importance of Celebrex to Pfizer is indisputable.
It is one of the company’s best-selling drugs, racking
up more than $2.5 billion in sales, and was prescribed
to 2.4 million patients in the United States last year
alone.
The drug is the last of the so-called COX-2 inhibitor
pain drugs, after Vioxx and Bextra were withdrawn in
2004 and 2005 because of safety concerns.
Some of the Celebrex’s detractors contend that its
risks are still not fully understood, and argue that
Pfizer is dragging its feet on a study — now nearly
six years old — evaluating the drug’s heart risks. The
study is scheduled to end in May 2014, the same month
that Celebrex loses its patent protection and sales of
the drug are expected to plunge.
Then and now, Pfizer has defended its decision to
release partial results from the 2000 study and denies
any intent to deceive. Company officials have said the
drug has demonstrated its worth and safety. The proof,
they say, is that 33 million Americans have taken it.
“The bottom line is Celebrex is a very important
option for many of these patients,” said Dr. Steve
Romano, head of the medicines development group in
Pfizer’s primary care unit.
The decision by Pfizer and Pharmacia to withhold
crucial data became widely known in 2001, after the
Food and Drug Administration released the study’s full
results. The revelations, along with similar reports
of withheld data by other drug companies, led to calls
for reforms in the way data from clinical trials is
published, including in The Journal of the American
Medical Association, which ran an article featuring
the partial results from the study.
The withheld data also led to a lawsuit, filed in
2003, by several pension funds that charged that by
handling the results the way they did, Pfizer and
Pharmacia had misled investors and were responsible
for a drop in Pharmacia’s stock value when the full
results were revealed.
Lawyers for Pfizer and for the pension funds declined
to comment. In a statement, company officials said
they were confident they would prevail when all the
evidence was heard. “The few documents handpicked by
lawyers suing Pfizer and being reported by The New
York Times are not a fair representation of this body
of evidence,” the company said.
The documents show that in February 2000, Pharmacia
employees came up with a game plan on how they might
present the findings once they were available.
“Worse case: we have to attack the trial design if we
do not see the results we want,” a memo read. It went
on: “If other endpoints do not deliver, we will also
need to strategize on how we provide the data.”
Another document, a slide, proposed explaining poor
results through “statistical glitches.”
Pfizer officials said the memo appears to reflect
discussions by some Pharmacia employees about both the
Celebrex study and a similar study of Vioxx. The
slides, the company said, appeared to have been
prepared before the results were known and discussed
several situations.
While officials were boasting of the study’s success,
employees behind the scenes were questioning its
value. In September 2000, Dr. Emilio Arbe, a Pharmacia
associate medical director, expressed his
reservations.
After describing the decision to use the limited
results as “data massage,” Dr. Arbe wrote, “I wouldn’t
feel too comfortable presenting a fudged version of
the facts.”
In May 2001, Dr. Mona Wahba, who worked on Celebrex,
sent an e-mail to colleagues describing as
“cherry-picking” a new analysis that also used six
months of the results. Pfizer officials said Dr.
Wahba’s e-mail was sent after the full study became
known. In a deposition, Dr. Wahba said she did not
recall what she meant.
Dr. Samuel Zwillich, who wrote the “hook, line and
sinker” e-mail, testified in another deposition that
his comment probably had to do with his concerns
around a lesser claim that Celebrex led to less blood
loss than other drugs. Through a Pfizer spokesman, he
declined to comment.
Pfizer has argued that presenting the limited data was
legitimate because so many people taking a comparison
drug, diclofenac, dropped out, biasing the later
results.
The controversy over the safety and effectiveness of
Celebrex continues today. Celebrex and Vioxx, which
was made by Merck, brought in billions in sales almost
as soon as they were introduced in the 1990s.
But the excitement skidded to a halt in 2004, when
Merck withdrew Vioxx after studies linked it to an
increased risk for heart attacks. Some studies
indicated that Celebrex, too, carried elevated risks.
In part to address those concerns, Pfizer announced in
2005 that it was starting a trial that would compare
the heart risk for Celebrex with ibuprofen, the drug
in Advil and Motrin, and naproxen, which is sold as
Aleve. The trial is not expected to be finished until
2014 when the Celebrex patent expires.
Dr. Steven Nissen, the Cleveland Clinic cardiologist
who is overseeing the trial, said Pfizer has spent
hundreds of millions of dollars and enrolled 18,000
patients. Recruiting has been difficult, he said, in
part because European Union countries have barred
patients with heart risks.
Dr. Nissen dismissed claims from critics that Pfizer
has been delaying the trial out of fears about its
outcome. “The last thing in the world I want to do is
to be sitting here twiddling my thumbs with a public
health concern,” he said.
Others were not so sure.
“One could draw conclusions,” Dr. Alastair J. J. Wood,
who was chairman of the F.D.A. advisory panel that
examined COX-2 inhibitors, said recently. He is a
partner at Symphony Capital, which invests in drug
development. “It clearly would have been nice to have
had this information long ago.”
Despite its success, Celebrex’s place among pain drugs
is not settled. According to Pfizer, 93 percent of
insured patients have access to Celebrex.
Some doctors said Celebrex has advantages because it
can be taken once a day and studies have shown that it
causes less stomach discomfort than other drugs,
although some have argued those types of findings are
not always reliable.
“You’re dealing with softer, subjective endpoints,”
said Garret FitzGerald, chairman of pharmacology at
the University of Pennsylvania.
There is still no clinical proof that Celebrex is
better at preventing serious gastrointestinal
injuries.
Dr. David Borenstein, who conducted some trials of
Celebrex for Pharmacia, said the drug relieved pain in
some patients when other drugs failed. “It’s easy to
talk about theoreticals when you’re not hurting,” he
said.
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