[e-drug] Drug trials

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E-drug: Drug trials
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[More food for thought. Distributed as fair use. HH]

Dying medicine boss: 'Drug trials are pointless ... and unethical'

Sunday Herald, UK - 1 March 2003
Sarah-Kate Templeton

For the past 40 years Professor David Horrobin has been developing
new medicines. In 1977 he founded Scotia Holdings, which was once
one of Scotland's most promising biotechnology firms. But today, as
the drug company boss is dying of cancer, he has decided to expose
the unethical experiments that his industry carries out on patients.
Horrobin reveals that patients recruited to clinical trials are prescribed
highly toxic drugs with serious side effects, while they stand little
chance of benefiting personally. He says that only around one in 30
patients on trials will respond positively to treatment, but that
participants are not informed of this slim hope.

Horrobin, who is currently chairman of Stirling-based firm Laxdale Ltd,
which develops new psychiatric drugs, claims that pharmaceutical
companies even deliberately recruit more patients than they need for
trials so that there are too few sufferers left for competitors to test
rival drugs.

He also reveals that promising cancer treatments are not available to
patients because, unless they are a completely new compound and
qualify for a patent which will secure profit from their sale, no
company will pay for them to go through the lengthy trial process. 

Two years ago Horrobin was diagnosed with lymphoma, cancer of the
lymph tissue. As the cancer was at an advanced stage, he was told
that he could not realistically expect to live more than six months. 

In a paper in the Lancet medical journal, which was fast-tracked for
urgent publication, he writes: 'I entered a universe parallel to the one
in which I had lived for 40 years. I became a patient and suddenly saw
everything from the other side. I discovered a whole new attitude to
clinical trials and experimental treatments.

'I believe that patients who are asked to volunteer for large trials in
cancer or other lethal diseases are being misled. Most such trials
cannot be justified on ethical grounds.'

He points out that large trials are needed to show up a small
improvement on present treatments. 'If a trial has to be large, say
more than 100 patients, it is large only because the expected effect
size is very small. That means that most patients entering the trial
have little or no chance of receiving benefit. With the toxic nature of
many oncology [tumour] treatment regimens, there may well be a
substantial chance of harm. Although the risk of harm is usually well
described in patient information leaflets, almost nothing adequate is
ever said about the assumed effect size and the real chance of benefit.
Almost all patients volunteering for most trials in oncology are
doomed: at best they can expect little benefit. They are not usually
being properly told about this low expectation.'

As a cancer patient, Horrobin came to the conclusion that it was not
necessarily in the best interests of the sufferer to take part in trials.
'In
view of the frequently severe adverse events, usually much more
predictable and reliable in their occurrence than ... a therapeutic
response, a decision on the patient's part not to be treated is not
irrational. I learned that few patients are made aware of this fact: that
is unethical.

'Patients with lethal diseases want to get better, not to have their lives
extended by a few weeks or months at great cost in toxicity and time
in treatment.'

The most damning allegation in Horrobin's paper is that pharmaceutical
companies actually try to sign up as many patients as possible to their
trials so that competitors have difficulty finding sufferers to test rival
drugs. Speaking from the Western General Hospital in Edinburgh where
he is currently undergoing treatment, Horrobin insisted he had been
present at industry meetings where this unscrupulous practice had
been discussed.

'For the past 20 years I have been working in the pharmaceutical
industry. Although everyone in the industry will deny it, and I doubt
whether there is documentary evidence of this statement anywhere, I
know that several of the larger firms use overpowered trials as a way
of keeping competitors out of that particular subject. Especially with
less common cancers, if a company, by manipulating the power
calculations, can recruit for a trial several times more patients than is
necessary, then they will gain a clear competitive advantage by
making it more difficult for rivals to recruit.'

Horrobin added that hospitals conducting clinical trials for
pharmaceutical firms profit financially from the experiments -- without
necessarily telling the patients.

'Most patients entering most oncology trials will be dead before the
results are known. But the institutions in which they are being treated
probably benefit greatly financially. Most patient information leaf-lets
do not tell them either fact. This omission is unethical.

'I cannot find any patient information which states that the hospital
will benefit from that patient taking part in the trial and by how much.
This could be between ?3000 and ?20,000 per trial.'

Putting new medicines through trial is expensive, and the costs are
covered only when the drug can be sold at a high profit. If a medicine
is not considered novel enough to be granted a patent, guaranteeing a
high price when it comes on the market, it will not be financially
worthwhile pursuing. Unprofitable but helpful therapies are therefore
denied to patients, says Horrobin. 

The former professor of medicine at Montreal University says his
knowledge has allowed him to access medicines that would not be
available to most patients. 

'The high cost of large trials means that they can be done only on
patent-protected new chemical entities. Since such companies have to
seek a return for investment, trials will be conducted for only a tiny
part of the wide range of potential cancer therapies. Cancer patients
are, of course, not told that such a small part of potential therapies is
open to them.

'The Western General has collaborated with me completely. I have had
no difficulty using the treatment I wanted -- but I have a special
position in that I am running a pharmaceutical company.'

Charles Warlow, professor of medical neurology at Edinburgh
University and a consultant at the city's Western General hospital, is a
staunch advocate of clinical trials. But even he admits he refused to
take part in a clinical trial himself when he was diagnosed with colon
cancer.

'I declined to be randomised in a trial of chemotherapy after my
carcinoma of the colon was removed seven years ago. I was too
frightened by the side effects of the new treatment and didn't think
the risk could be worth the likely benefit so I stuck with the old
treatment. So far so good.

'The problem is that if a benefit is very small, does it offer anything to
patients and is it worth the side effects of treatment? It depends. If
there is a very small benefit it may be worthwhile if the drug is cheap,
easy to take, and there are no or very few side effects -- like aspirin to
prevent another stroke in a stroke survivor. Yet with some cancer
drugs there may only be a small advantage, allowing patients to live
for just a few weeks or months longer, but they may have to put up
with some pretty toxic side effects. In that case it may not be worth it
and I don't know if patients are always informed of that -- although I
myself certainly was.'

Warlow added that patients in clinical trials generally get better care
than those in routine practice because they are closely followed up by
doctors. 

Jim Eadie, director of the Association of the British Pharmaceutical
Industry in Scotland, said: 'Clinical trials are essential to develop new
and better treatments for patients, and play a crucial part in ensuring
that the UK and Scotland are at the forefront of the development of
modern treatments and research.

'It is important that trials involve as many patients as possible in order
to obtain the most accurate, scientifically valid data. Companies carry
out multi-centre clinical trials all over the world and are not restricted
to seeking patients only in the UK. It is therefore impossible for any
single company to sign up all patients with a particular condition for its
clinical trial work.

'It is true that sometimes medicines may be withdrawn at a late stage
in development, but this will invariably be because of problems
associated with safety and efficacy, not because of imminent expiry of
patent life.'

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