- VICTIMS
OF DRUG THAT TOOK A HIDDEN TOLL Page
1
The
Sunday Times (London) August 21 2005
SPECIAL
INVESTIGATION BY BRIAN DEER
WHEN
Kenneth Wood died of a heart attack two years ago, on
the day he was supposed to go on holiday to America,
his wife Margaret blamed herself.
Should
she have given him an aspirin, she wondered, to thin
his blood as he lay complaining of chest pains? The
ambulance crew had done that straight away. Could she
have done more to galvanise the hospital? The
doctors, she felt, had looked confused.
“The
shock was that he was so active,” said Margaret,
64. “He used to go bowling six nights a week,
right up until the day before he died.”
Last
September she got another shock when Vioxx, a
painkilling “wonder drug”, was taken off
the market after a clinical trial in America had
shown a link to heart attacks.
Wood,
71, a retired laboratory technician from Madeley,
Shropshire, had been taking part in British trials of
Vioxx when he died. The research was designed to
establish whether the drug could be extended from its
main purpose, relieving arthritis, to the prevention
of colon cancer.
In
doing so, Wood became one of numerous victims of a
medical cataclysm highlighted this weekend by a court
case in Texas, which saw the drug’s
manufacturer, Merck Inc of New Jersey, ordered to pay
£141.1m in damages to the widow of another Vioxx
patient.
Dozens
of British lawyers are now soliciting clients, while
some experts calculate the global toll linked to
Vioxx at up to 60,000 deaths. “This,” Dr
David Graham, a senior US Food and Drug
Administration (FDA) official, told a stunned Senate
committee last November, “would be the rough
equivalent of 500 to 900 aircraft dropping from the
sky.” He described it as “what may be the
single greatest drug safety catastrophe”.
Although
Margaret Wood has no plans to sue anyone, some
lawyers believe she could have grounds. A Sunday
Times investigation into the British connection to
the Vioxx project has established that her husband
was never told of all the possible risks when he was
recruited for the trial.
This
is the essence of what emerged from the court near
Houston — that Merck did not disclose to
patients all it knew about problems with the drug.
Margaret
did not know, for example, that a doctor working on
the trial had reported to Merck that the drug trial
was “probably” to blame for Wood’s
heart attack. “I’m very, very angry,”
said Margaret when I showed her confidential
documents last month. “I wasn’t aware that
there were any risks at all.”
Her
husband died in November 2003, 18 months after
volunteering for the research. The trial, called
project “Victor”, was financed by Merck.
Nor
did Margaret know that evidence of Vioxx’s
potential dangers had first been noted four years
earlier. Even after this, the drug was backed by much
of the medical establishment in America and Britain.
Just
six months before Wood’s death, Britain’s
leading authority on painkillers had dismissed rising
fears over heart attack deaths connected to Vioxx as
“speculation”.
The
Wood case is part of a far bigger scandal now
threatening to engulf Merck. When Vioxx was
withdrawn, 20m people around the world, including
400,000 in Britain, were using the drug. Doctors have
formally reported the deaths of 103 people in
Britain, but the real figure may be as high as 2,000
according to some experts.
Why
was such a potentially dangerous drug allowed to be
prescribed so widely in Britain? Why was it backed so
enthusiastically by experts such as Professor Michael
Langman, one of the leaders of the Victor trial and
an expert on painkillers? The answers are both
complex and distressing. They begin with a paradox
that Langman had been struggling with for more than
20 years.
LANGMAN,
a former dean of Birmingham University’s medical
school, became a figure of great influence in 1987 as
one of the 36 members of the government’s drugs
watchdog, the Committee on Safety of Medicines (CSM).
Painkillers
have long been Langman’s specialist interest,
particularly aspirin and similar drugs such as
naproxen and ibuprofen, known collectively as
“non-steroidal anti-inflammatories” or
NSAIDs. Although they are effective, particularly in
osteoarthritis, they can also cause fatal stomach
ulcers and perforations.
When
Merck announced in 1999 that it had developed a
similar drug without these side effects, Langman was
understandably impressed. The new drug was based on
Nobel prizewinning research by Sir John Vane, a
British pharmacologist who had found that aspirin
blocked two chemical messengers. One triggered the
heat and pain of inflammation, while the other
protected the stomach from ulcers. By blocking one
but not the other, it ought to be possible to give
relief without the usual risks.
Few
new medicines are truly “miracle drugs” but
this was how Merck sold Vioxx. To advance this image
it recruited an army of consultants, Langman being
among the most distinguished.
In
April 1999 he sat with the Merck delegation when FDA
advisers assembled at the Gaithersburg Holiday Inn in
Maryland to consider the company’s application
for a marketing licence.
“In
my country there are hundreds of deaths a year —
in all there are thousands — from NSAIDs
complications,” he told the meeting. “It is
the critical issue and if we have information that
bears upon it I have a feeling, as somebody with an
interest in public health, it’s our duty to make
it known.”
Nine
days later the CSM approved the drug for marketing in
Britain. A leaflet aimed at British doctors stated:
“In eight pooled studies of up to one year,
Vioxx (average dose 25mg) reduced the risk of
developing upper GI (gastro-intestinal) perforations,
ulcers and bleeds by more than half compared to
NSAIDs.”
Although
FDA staff registered “serious concerns”
about the analysis, Langman became the new
drug’s champion. In one journal he declared that
Vioxx-type drugs “are almost certainly
associated with lower risks of ulcer and its
complications, and probably no risk at all”. In
another he later denounced rising fears over heart
attacks as “a flurry of unjustifiable
speculation and controversy”.
In
2001, at the peak of the Vioxx hype, Merck reportedly
spent $160m advertising the drug. In Britain, where
direct advertising is banned, the promotion was
almost wholly through doctors.
“The
world of relief is about to change,” screamed
promotions issued for Vioxx’s British launch
(including a coupon offering doctors a free clock).
“True once-daily dosing for osteoarthritis
patients . . . Selective, strong, simple.”
Merck
also sought ways of broadening the market for the
drug by demonstrating that, like aspirin, Vioxx was
effective for more than just arthritis. Doctors
prescribed it to reduce the inflammation caused by
sports injuries, and in particular it seemed to have
potential for inhibiting tumours, for example in
colon cancer.
So
while an American Merck trial code-named
“Vigor” compared Vioxx — known
generically as rofecoxib — with the painkiller
naproxen for the treatment of rheumatoid arthritis,
another trial — “Approve” —
tested whether colon cancer could be stayed.
In
November 1999 the safety committee monitoring Vigor
met to discuss increased blood pressure, “excess
deaths and cardiovascular experiences”.
