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BRIAN DEER:
HARD SELL Page 5
Confronted by
Elion's world-weary eyes and no-nonsense charm, it is
certainly ill-mannered, and perhaps even cruel, to
say anything ill of her offspring. In stories of a
childhood in Brooklyn, she talks about how a
favourite grandfather died from cancer, propelling
her into a lifelong quest. It is a similar story with
Hitchings, who grew up on the Pacific coast of
Washington state, and was 12 when his father died.
For some 45 years this pair shared a lab, sometimes
seven days a week.
But, as was
revealed last week in the first part of our
investigation, research suggests that three of
Wellcome's big four products - the antibiotic
Septrin, the Aids drug AZT, and the herpes treatment
acyclovir - have all been promoted by the
company’s marking people beyond the best medical
opinion. Much of their yield has come from
prescriptions to patients who might not need them, or
for whom they were unduly dangerous.
It can take
years for independent investigators to get the
measure of a drug’s benefits and risks. So it is
the older product, Septrin (also branded as Bactrim),
that has prompted the most forceful concerns. In this
antibiotic, a relatively safe and effective compound
called trimethoprim (invented by Hitchings) was mixed
with a more dangerous, and largely redundant, sulpha
chemical (sulphamethoxazole), in a controversial
marketing deal.
Since its
launch in the late 1960s, research suggests that this
combination drug may have been associated worldwide
with what could be thousands of deaths and injuries.
Even during the past week, people have contacted The
Sunday Times to talk of their personal misfortunes.
One mother
complained that her four-year-old son had been
rushed, close to death, to hospital after taking
Septrin for a chest complaint. Another user recounted
how her life had been "ruined" from a
chronic syndrome that set in immediately afterwards.
Meanwhile, Wellcome’s solicitors said that our
reports "appalled" their clients, and that
they were considering their legal position.
The fourth big
earner - the gout drug allopurinol - was not examined
in last week's reports. It too has greatly helped a
relatively defined group of patients, but was
marketed far beyond its best usage. Like the others
among Elion and Hitchings’s creations, it
reveals a system in which some patients can be
prescribed medicines for whom advantages and dangers
may be skewed.
Gout is a
disease for which there is still no cure, caused by
an excess of uric acid in the blood
("hyperuricaemia"). It mostly shows in old
people, when it super-saturates tissues, sometimes
causing swellings and pain. In its chronic state, the
acid forms crystals - particularly in the kidneys and
joints - producing deformities and a condition like
arthritis.
Elion and
Hitchings conceived allopurinol almost by accident,
while searching for cancer treatments. But in 1956,
they stumbled on its effects, and so a gout drug was
born. It was the kind of mix'n'match discovery that
was common in those days, and which even now makes
Hitchings smile.
"We said:
'Now we've got the drugs,"' he chortles, during
an interview in his office, along a wide, carpeted
corridor from Elion’s. "'All we've got to
do is find the diseases that go with them."'
When
allopurinol was first marketed, in 1963, it seemed
like an unqualified success. Many thousands of gout
sufferers (Elion included) found that the drop it
brought to uric acid levels meant that the disease,
at last, became bearable. Although reliance on it may
have distracted from much-needed diet and lifestyle
changes, it at least relieved symptoms for most
users.
But even the
commonest drugs are not free of downsides, and it
soon became clear that some patients on allopurinol
found that it caused rather than relieved
gout symptoms. Side-effects, meanwhile, could range
from mild skin rashes to fatal blood disorders and a
hypersensitivity syndrome.
In 1970, The
New England Journal of Medicine - the world’s
top medical publication - reported the first
strongly-linked death. It was of a 72-year-old man
who had been diagnosed with gouty arthritis in 1944,
but who was stable until discovering allopurinol.
By January
1986, 22 deaths linked with the drug had been
published in the medical press - and were reviewed in
the journal Arthritis and Rheumatism. This noted
"significant morbidity and mortality associated
with the allopurinol hypersensitivity syndrome,"
and warned doctors to temper their prescribing.
In the intervening years, however, Wellcome had
promoted the drug heavily, with advertising and sales
visits to doctors. These advocated its use not just
for people with gout, but also for those with only
raised uric acid levels - so called
“asymptomatic hyperuricaemia”. In the same
way that the company was later to argue that AZT
should be used to prevent Aids developing in
HIV-positive people, rather than merely for treating
the sick, allopurinol was prescribed to the much
greater patient numbers who were only predisposed
to gout.
"Remember
Zyloprim the original (allopurinol)," was one
popular advertising campaign for doctors, which kept
the complexities to mandatory small-print. Another -
which ran at the front of the Journal of Rheumatology
continuously between 1974 and 1986 - declared
bluntly: "In hyperuricaemia or chronic gouty
arthritis, Zyloprim."
Although such
ads may have been technically accurate, the increased
consumption that they encouraged inevitably raised
the numbers exposed to side-effects. While most
patients handled allopurinol well, studies showed
that about 2% experienced adverse events, with one
hospital survey finding that, of every 260 patients
treated, one had a life-threatening reaction.
Other research
showed that most of those who suffered or died,
should not have been taking the drug in the first
place. "The vast majority of patients, both in
our series (7 of 8), and reported in the literature
(51 of 59), who developed allopurinol
hypersensitivity, did not have proper indications for
receiving the drug," reported researchers in the
journal Arthritis and Rheumatism. "Serious and
often fatal allopurinol hypersensitivity is a high
price to pay for inappropriate therapy."
*****
