News - Come out of the past

Scientists demand updated policies


Safer Medicines Trust has joined forces with 21 senior scientists to call on the Prime Minister and Health Secretary to compare animal tests for drug safety with newer tests based on human biology.

An open letter has been printed in medical journal The Lancet and is reproduced below.

The matter was also covered in the Daily Mail and on Sky News as well.

 

The Lancet, Volume 377, Issue 9781, Page 1915, 4 June 2011

doi:10.1016/S0140-6736(11)60802-7

Open letter to UK Prime Minister David Cameron and Health Secretary Andrew Lansley on safety of medicines

 

Kathy Archibald a, Robert Coleman b, Christopher Foster c, on behalf of 19 other signatories

We are writing to you as a group of clinicians and scientists to express our concern about the escalating problems of drug failures and adverse drug reactions. The UK pharmaceutical industry is in crisis, as the departure of Pfizer from the Sandwich site makes plain. Likewise, health care is in a web of crises, many of which are intimately linked to the pharmaceutical industry's major problems.

Adverse drug reactions have reached epidemic proportions and are increasing at twice the rate of prescriptions.1 The European Commission estimated in 2008 that adverse reactions kill 197 000 EU citizens annually, at a cost of €79 billion.2 The cost of new medicines is rising unsustainably, creating an ever-increasing burden on the National Health Service (NHS). Meanwhile, many increasingly prevalent diseases, such as Alzheimer's disease, diabetes, many cancers, and stroke, remain without adequate treatments.

The major reason for the rising cost of new drugs is the fact that more than 90% of them fail in clinical trials.3 Companies need to recoup the cost of development not only for the drug that succeeds, but for the nine others that fall by the wayside.

It is increasingly clear that an important factor contributing to these problems is the over-reliance of the pharmaceutical industry on the use of animals to predict drug behaviour in man. The stark differences, not only in the diseases of different animal species, but also the ways that they respond to drugs, are now well known. Many studies have shown that animal tests frequently fail to translate to the clinic, with estimates of their ability to predict effects on people as low as 37—50%, or no better than the toss of a coin.
4

Our reliance on animals to establish safety results in the exposure of clinical volunteers and patients to many treatments that are at best ineffective and at worst dangerous. Take for example the notorious Northwick Park clinical trial drug, TGN1412, that left six young men in intensive care in 2006. This drug was demonstrably safe in monkeys at doses 500 times higher than those that nearly proved fatal to the volunteers.5 Soon after the disastrous trial, an assay that used human cells was developed to predict such an immune system over-reaction.5 Had this assay been in use before human beings were exposed, the trial would never have taken place. Surely the time has come for there to be a rigorous assessment of the ability of such human-based tests to improve on the deeply flawed, animal-based approaches in current use?

We call on the UK Government to initiate a comparison of a set of human-biology-based tests with those currently used, as proposed in the Safety of Medicines Bill 2010—11,6 to see which are more effective for predicting the safety of medicines for patients. Several new technologies promise increased clinical predictability as well as substantial improvements in efficiency and cost. The Bill does not propose any replacement of animal tests, merely their assessment of fitness for purpose. 148 Members of Parliament have already signed a motion7 in support of this proposal.

Some of us recently made representations to the UK Department of Health, and were told that the Government believes that human-biology-based systems have not been established as being more predictive than are animal studies for developing safer medicines. We agree, but that is because no rigorous examination of such systems has been undertaken. The very purpose of the proposed comparison is to initiate such an examination, which is urgently necessary for the sake of the NHS, the pharmaceutical industry, and, most importantly, patients.

We urge you to act now to ensure that the best technologies currently available are used to establish the safety of medicines for patients.

We declare that we have no conflicts of interest.

References

1 Lakhani N. Special report: prescription medicines. The Independent Oct 21, 2007. PubMed

2 Anon. Strengthening pharmacovigilance to reduce adverse effects of medicines. Brussels: European Commission, 2008. http://ec.europa.eu/health/files/pharmacos/pharmpack_12_2008/memo_pharmacovigiliance_december_2008_en.pdf. (accessed May 10, 2011).

3 US Food and Drug Administration. Innovation or stagnation: challenge and opportunity on the critical path to new medical products. http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/CriticalPathOpportunitiesReports/ucm077262.htm. (accessed May 10, 2011).

4 Perel P, Roberts I, Sena E, et al. Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ 2006; 334: 197-200. CrossRef | PubMed

5 Stebbings R, Findlay L, Edwards C, et al. “Cytokine storm” in the phase I trial of monoclonal antibody TGN1412: better understanding the causes to improve preclinical testing of immunotherapeutics. J Immunol 2007; 179: 3325-3331. PubMed

6 House of Commons. Safety of Medicines Bill. London: Stationery Office, 2010. http://www.publications.parliament.uk/pa/cm201011/cmbills/059/2011059.pdf. (accessed May 10, 2011).

7 House of Commons. Early day motion 475: safety of medicines. http://www.parliament.uk/edm/2010-11/475. (accessed May 12, 2011).

a Safer Medicines Trust, PO Box 62720, London SW2 9FQ, UK

b 27 Wodehouse Terrace, Falmouth, UK

c Liverpool University, Division of Pathology, Liverpool, UK

News reports
Million a year in hospital over reactions to medicines
D. Mail 3.6.11

Bad reactions to medical drugs have reached epidemic levels. Around 1 in 15 hospital admissions each year (more than a million patients) are caused by adverse medical drug reactions, says the Safer Medicines Trust, based on official figures. They say the current system of testing drugs for humans on animals is failing & is exposing patients to “dangerous treatments.”

It wants new technologies based on human biology to be used. Their letter to the Prime Minister & Health Secretary is published in “The Lancet.” 6 young men were left in intensive care by trial drug in 2006, which was ‘demonstrably safe in monkeys at doses nearly 500 x higher than those that nearly killed the volunteers” the Safer Medicines Trust said.

Mounting Fears Over Adverse Drug Reactions
Yahoo. 4 June 2011.

Scientists have written to the Prime Minister and Health Secretary Andrew Lansley expressing their concern about drug failures and adverse drug reactions.

More than 10,000 people die every year from bad reactions to prescribed treatments and scientists are calling for a fresh approach.

The experts believe adverse drug reaction has reach "epidemic proportions" amid rising costs in prescriptions.

Drug testing on animals before they are used on humans is being partly blamed.

The letter claims many increasingly prevalent ailments, like Alzheimer's disease, diabetes, cancers and stroke, remain without adequate treatment.

An important factor contributing to these problems is the over-reliance of the pharmaceutical industry on the use of animals to predict drug behaviour in humans.

The letter, published in the Lancet, adds studies have shown animal tests frequently fail to translate to the clinic.

Scientist Tony Dexter, who runs a research lab in Cheshire and is a signatory, said: "A fundamental problem is that a rat is not a human.

"They are different sizes, have different metabolisms and have different diets, so using animals to predict effects on humans is difficult.

"Fifty percent of compounds that prove to be safe in rats prove not to be safe in humans, so it really is the toss of a coin."

The experts are now calling for the use of more human biology-based experiments where chemicals are tested on human cells to see how people might be affected by new treatment.

The annual costs of treating patients who have had bad reactions to their treatment is around £2bn a year.

It is believed millions of deaths could be prevented with the use of new technology available. Some 148 members of parliament have signed a notion is support of the proposals.

A spokesman from the regulatory body Medicines and Healthcare products Regulatory Agency said: "The use of non-animal testing has been extended wherever possible and the MHRA will continue to encourage this approach.

"It is very important to recognise that at present there are no laboratory methods available to totally replace animal testing of medicines."

In 2008, the European Commission estimated adverse reactions to treatment kill almost 200,000 EU citizens annually at a cost 79 billion Euros.

The news comes at a time when costs of new medicines are rising creating an ever-increasing burden on the NHS.