Animal Testing and Human Trials: Alternatives or Complements?

The Animal Justice Project, a British-based animal rights group, is no stranger to misinformation. Previously we have debunked their factual errors regarding malaria studies in Sweden and eye injury studies. There was also the time they produced a press release which suggested 52^oC (125^oF) was the same as boiling water (which admittedly might be true if you tried to make a cup of tea in the lower stratosphere).

Recently on their website, a blog by Judith Snaith has been put up. The blog is a mash up of animal rights myths and misinformation, but one line was of particular interest.

More than 100,000 humans are killed yearly by prescription drugs that passed animal testing. Animal research is not the final phase, 90 per cent of drugs that pass the animal tests fail in human trials. So if we have to test on humans to be accurate, can we not skip out the middle monkey?

Let’s break this down bit by bit. The figure of 100,000 is an American one (Lazarou et al, 1998) with the figures for the UK approximated at around 10,000 (Pirmohamed et al, 2000) using a similar methodology. We have mentioned the flaws in these figures in our “Animal Rights Pseudoscience” page:

The statistic of 100,000 deaths in a year is taken from a 1998 meta-analysis by Lazarou and colleagues that examined rates of adverse drug reactions (ADRs) observed in 39 studies undertaken between 1966 and 1996 (Lazarou et al, 1998). The methods used in this meta-analysis were subsequently criticised for failing to adequately take into account differences between the 39 studies examined, a failing which may have lead to an over estimation of the number of deaths due to ADRs (Kvasz et al, 2000).

Between 2001 and 2002 Pirmohamed and colleagues analysed admissions to two hospitals in Merseyside, in order to determine if the cause of admission was an adverse drug reaction (Pirmohamed et al, 2000). Their results indicated that ADRs accounted for 6.5% of hospital admissions, and that ADRs may be responsible for up to 10,000 deaths a year in the United Kingdom. The study also found that:

• 95% of ADRs were predictable from the known pharmacology of the drugs (i.e. from animal testing and human clinical data).

• A large majority of ADRs were caused by older drugs.

• About 70% of ADRs were either possibly or definitely avoidable.

So a large amount of these deaths come down to human error as the adverse drug reactions were both predictable and avoidable.

Judith mentions that these 100,000 deaths came from drugs which had passed animal tests. What she chooses not to mention is that these 100,000 deaths came from drugs which had also passed clinical trials in humans. There is no logical reason to put these deaths at the feet of animal tests – particularly as the animal tests do not check for the common causes of drug deaths – accidental overdose, negative drug-drug interactions from secondary medications, incorrectly prescribed medication etc.

Judith then goes on to mention that 90% of drugs that pass animal tests go on to fail in humans:

Animal research is not the final phase, 90 per cent of drugs that pass the animal tests fail in human trials

We’ve definitely seen and debunked this statistic before. The inference is that animal tests are not effective as many drugs fail later on. Prof Lovell-Badge explains some of the many flaws in this argument. Firstly, there is a similarly high failure rate in the human trials:

Consider that of all the drugs which pass Phase 1 clinical trials in humans, 86% will fail in later stage human trials. Yet, we do not hear activists suggesting that humans are an entirely inappropriate model for drug development (though we should note that one human is not a perfect model for another).

Furthermore, this whole argument is premised on a misunderstanding of the different role of animal and human trials:

The role of preclinical animal tests is to check if the drug offers any potential therapeutic value and, importantly, if it is safe enough to move to Phase 1 trials in humans. This does not even mean free of all side effects, but to learn whether a drug can safely be given to humans and at what approximate dosage.

Put another way, every stage of drug testing acts as a safety barrier for dangerous drugs being sold. Pre-clinical in vitro tests, pre-clinical animal tests, Phase I clinical trials, and Phase II-III clinical trials all work successively to remove potentially dangerous compounds from reaching the market. These are not their only functions, animal tests may help assess appropriate therapeutic doses, which can be later refined during clinical trials. These tests (animals and humans) may also help discover potential side effects (this does not mean the drug will be rejected – it depends on the seriousness of the condition it is intended to treat).

Judith Snaith goes on to combine her two assertions to claim that we don’t need to do the animal tests – we can just move straight to humans.

So if we have to test on humans to be accurate, can we not skip out the middle monkey?

This ignores the huge number of dangerous compounds which are removed from the drug development process because they show toxic effects in animals. To skip this step would be to allow these compounds to be trialled in humans. Furthermore, when one safety check doesn’t guarantee safety, that doesn’t mean removing the check makes anyone safer.

Animal testing is not an alternative to human trials, it complements it. Medieval castles had high walls and soldiers in them – both protect the defenceless people in the keep. Sometimes high walls and soldiers were not sufficient, and the castle was sacked, but no one would conclude that high walls were pointless and that everyone would be safer if there were just the soldiers. In reality, doing away with the castle would mean more soldiers would die, just as doing away with animal tests would likely lead to more deaths in Phase I and II clinical trials; the consequence of this would be that fewer people would volunteer for clinical trials (just as fewer soldiers would wish to defend a low-walled castle).

We use a variety of methods in biomedical science – computer simulations, tissue studies, animal models, clinical trials, epidemiology etc. Different methods can teach us different things and the results are often used in combination to build our knowledge and understanding of physiology and disease. The same is true in safety testing – all methods of screening drugs have advantages and drawbacks, but if we use them effectively, in combination, we can see that safe and effective drugs make it to market.

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