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

March 6, 2003

http://www.sundayherald.com/31817

Exclusive: Volunteers stand little chance of recovery

Treatments kept from public

Companies scupper rivals

By Sarah-Kate Templeton, Health Editor

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 pub

lication, 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 inform ation 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 irrat ional. 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 alleg ation 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 cal culations, 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 addded 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 ther apies 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 clin ical 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 assoc iated with

safety and efficacy, not because of imminent expiry of patent life.'

, 'text' => '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.