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ANIMAL TESTING – MPs, GPs and scientists demand evaluation

Animal tests were made a legal requirement following the Thalidomide tragedy forty years ago, in the hope of preventing another such disaster. But have they lived up to their promise? Recently withdrawn arthritis drug Vioxx was safe and even beneficial to animal’s hearts but caused as many as 140,000 heart attacks and strokes in people – the biggest drug catastrophe in history.[1] Shockingly, adverse reactions to prescription medicines (all tested for safety on animals) are now the fourth leading cause of death in the western world: killing over 10,000 people a year in the UK and costing the NHS £466 million.[2] New human-based safety tests before and during clinical trials (such as microdosing) could prevent many of these deaths.

Compelling reasons to assess the efficacy of animal tests include:

• Several published studies assessing the prediction of drug side effects by animals have found them to be very poor predictors; correct only 5-25% of the time.[3]
• 92% of drugs fail in clinical trials, having successfully passed through animal studies.[4]
• Sophisticated new methods of assessing drug safety include human tissues, DNA chips, virtual metabolism simulators and microdosing with PET and AMS scanners.[5]
• A new study of animal and in vitro methods of predicting teratogenicity (potential to cause birth defects) spanning 40 years has found animal tests to be ineffective.[6]
• Scores of treatments for stroke have tested safe and effective in animals in recent years but not a single one has emerged as safe and effective for patients.[7]
• 82% of doctors in an independent survey in 2004 were “concerned that animal data can be misleading when applied to humans” and 83% would “support an independent scientific evaluation of the clinical relevance of animal experimentation.”[8]
• The Toxicology Working Group of the House of Lords Select Committee on Animals in Scientific Procedures in 2002 recommended that “the reliability and relevance of all existing animal tests should be reviewed as a matter of urgency.”[9]
• A 2004 paper in the British Medical Journal concluded that “the contribution of animal studies to clinical medicine requires urgent formal evaluation.”[10]
• The recent Health Committee inquiry into the influence of the pharmaceutical industry concluded that the regulatory standards for new drug approval require urgent review.[11]
• This Government came to power promising a Royal Commission on animal experimentation. Yet Home Office Minister Caroline Flint stated in 2004 that the Government “has not commissioned or evaluated any formal research on the efficacy of animal experiments and has no plans to do so.”[12]

State-of-the-art human-based tests could have prevented the Vioxx tragedy. The public deserves to be protected from another ‘Vioxx’ in future. Clearly, an assessment needs to be made of the relative performance of the various methods of safety testing available. Substantial evidence exists that animal tests are inadequate for the task but – incredibly – this has never been systematically investigated. The only responsible course of action is to evaluate animal testing scientifically, in an independent and transparent manner.

Says Science Director of Europeans for Medical Progress, Dr Jarrod Bailey, “The urgency of this evaluation cannot be overstated: people’s lives are at stake. The Government must act now to facilitate the conduct of this evaluation and undertake to act upon the results with due speed when the implications have become apparent.”

Says Mike Hancock, CBE, MP, “It is astonishing that animal testing has never been scientifically evaluated and the process is long overdue. We cannot have confidence in animal testing until a genuine assessment is conducted and the results made public.”

Supporting our call are: The Rt Hon Tony Benn, Dr Caroline Lucas MEP, Mike Hancock, CBE, MP, Norman Baker MP, Michael Meacher MP, Ann Widdecombe MP

References and notes:

[1] British Medical Journal 2004;329:1253
Dr David Graham, associate director of the FDA’s Office of Drug Safety, said an estimated 88,000 to 139,000 Americans had heart attacks and strokes as a result of taking Vioxx, as many as 55,000 of them fatal. The number, he said, far exceeds earlier disasters such as the 100 children killed in the United States by an elixir of sulfanilamide in the 1930s and the 5,000 to 10,000 children born in the 1960s with birth defects related to thalidomide. Both events led to sweeping regulatory changes.

[2] British Medical Journal 2004;329:15-19 Adverse drug reactions as cause of admission to hospital.
“Measures are urgently needed to reduce the burden on the NHS.”

[3] eg. Clin Pharmacol 1962;3:665-72
Zbinden, G (1991) Predictive value of animal studies in toxicology. Regul. Tox. Pharm. 14: 167-177
CMR Workshop – Animal Toxicity Studies: Their Relevance for Man Quay 1990 p 49-56 and p57-67
Spriet-Pourra, C and Auriche, M (Eds) 1994 SCRIP Reports PJB, New York
Garratini, S (1985) Toxic effects of chemicals: difficulties in extrapolating data from animals to man. Annu. Rev. Toxicol. Pharmacol. 16: 1-29
Zbinden, G (1993) Regul. Toxicol. Pharmacol. 17: 85-94
Calabrese (1984) Suitability of animal models for predictive toxicology: Drug Metab Rev 15: 505-523
Oser, BL (1981) J. Toxicol. Environ. Health 8: 521-642
Calabrese, EJ (1987) Principles of Animal Extrapolation. Wiley, New York
Olson, H., Betton, G., Stritar, J., and Robinson, D. (1998). The predictivity of the toxicity of pharmaceuticals in humans from animal data-An interim assessment. Toxicol. Lett. 102-103, 535-538
Regulatory Toxicology and Pharmacology 2000;32:56-67
Drug Metabolism and Drug Interactions 2000;16:143-155

Dr Ralph Heywood, former director of Huntingdon Research Centre, said, “… the best guess for the correlation of adverse reactions in man and animal toxicity data is somewhere between 5 and 25%.”

[4] Lester Crawford, FDA Commissioner, in The Scientist 6.8.04 “More compounds failing Phase I”

[5] Microdose studies (“Phase 0” clinical trials) were endorsed by the European Agency for the Evaluation of Medicinal Products in January 2003, and were shown to be highly effective at predicting human metabolic profiles in a trial culminating in March 2005. See www.microdosing.co.uk.

A ten-year international study proved that human cell culture tests are more accurate and yield more useful information about toxic mechanisms than traditional animal tests. Some companies (eg.www.asterand.com) focus on safety and efficacy assessments in human tissues. Others (eg. www.biopta.com) specialise in human pharmacological assessments during clinical trials, which could identify the cardiovascular hazards of a drug like Vioxx, for example, before it was marketed. Many companies specialise in virtual screening of drugs for potentially toxic effects. A wide range of predictive software is available, including complete clinical trial simulations.

[6] Biogenic Amines 2005; 19 (2): 97–145 Bailey et al; “The future of teratology research is in vitro”

[7] Nature Medicine 2002; 8 (1):5 Future of neuroprotective drugs in doubt, also Stroke 1990 21: 1-3

[8] Survey conducted by TNS Healthcare; see http://www.safermedicines.org/news/040903.shtml

[9] The Stationery Office, HL Paper 150-1, ISBN 0 10 412102 5, p70

[10] BMJ 2004; 328:514-517 Pound et al; “Where is the evidence that animal research benefits humans?”

[11] Press release from Health Select Committee, 5th April 2005. Publication of Report: The Influence of the Pharmaceutical Industry (HC 42-1).

[12] Written answer to Parliamentary Question from Mike Hancock, MP, March 31st 2004.