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 52oC (125oF) 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.

Would the French soldiers have taunted King Arthur if they didn’t have high walls? (Monty Python’s Holy Grail)

Speaking of Research

8 responses to “Animal Testing and Human Trials: Alternatives or Complements?

  1. However, over time, everybody abandoned living in castles altogether as it was decided that there were much better ways of doing things.

    • Tim nice but nice

      Over time, yes, but to extend your metaphor, many AR activists are suggesting Charles d’Albret would have won Agincourt if only he’d used Samsung lazer-guided APKWS rockets. Why use animals when you can use Dr McCoy’s Tricorder? It’s hardly clever, profound or responsible to predict today’s technologies will be surpassed, and it’s downright childish to pretend many of them can be surpassed today.

  2. It’s not an easy task to

    From one of the author’s links(https://speakingofresearch.com/2013/01/23/nine-out-of-ten-statistics-are-taken-out-of-context/):

    “The first thing to note is of those drugs which pass animal tests, 94% will fail during human clinical trials stages (Phases 1 – 3) … [The] number of drugs which have passed Phase 3 clinical trials ÷ number of drugs which have passed just animal tests = 1.2 ÷ 19.4 = 6.2% of drugs which reach Phase 1 trials are eliminated by Phase 1-3 clinical trials. 100 – 6.2 = 93.8% fail…. So the failure rate is actually higher than even the animal rights organizations suggest.”

    Totally sugar-coating it!!!

    “animal research apologists”

    Dear non-apologist, please forfeit the 25 years or so that have been granted to you thanks to animal research apologists. If you are not willing to do so, I understand. In that case, please refrain from accepting any medical treatments that were discovered thanks to animal research apologists. Unfortunately, that means nearly all of them. So, to reiterate… 85% failure rate (“a big one”) = nearly all modern medical advances.

    “Researchers who truly want to help and develop products that work need to and do understand this issue.”

    Huh?

  3. Juan Carlos Marvizon

    The vast majority of animal research does not consist of drug testing, but of basic science studies to increase our understanding of normal and pathological physiological processes. Some of that knowledge will be used to create new therapies to cure diseases. These may be based on medical compounds or may consist of other things like surgery, radiotherapy or physical therapy. Some of the research will be done for knowledge sake, which is a perfectly legitimate goal. This is explained in an article I wrote in this website (https://speakingofresearch.com/2013/01/17/animal-research-is-not-animal-testing/ ). Animal right activists want to frame the debate as drug testing, but this is not what animal research is all about.

  4. I’ve heard the 85% failure rate from many sources including someone who works for the USDA who was giving a talk about careers in the USDA. Not an animal activist by any means but he was talking about the issues of working in research. The 85% failure rate is a big one, there is no sugar coating it as much as animal research apologists may try. Researchers who truly want to help and develop products that work need to and do understand this issue.

    • From one of the author’s links(https://speakingofresearch.com/2013/01/23/nine-out-of-ten-statistics-are-taken-out-of-context/):

      “The first thing to note is of those drugs which pass animal tests, 94% will fail during human clinical trials stages (Phases 1 – 3) … [The] number of drugs which have passed Phase 3 clinical trials ÷ number of drugs which have passed just animal tests = 1.2 ÷ 19.4 = 6.2% of drugs which reach Phase 1 trials are eliminated by Phase 1-3 clinical trials. 100 – 6.2 = 93.8% fail…. So the failure rate is actually higher than even the animal rights organizations suggest.”

      Totally sugar-coating it!!!

      “animal research apologists”

      Dear non-apologist, please forfeit the 25 years or so that have been granted to you thanks to animal research apologists. If you are not willing to do so, I understand. In that case, please refrain from accepting any medical treatments that were discovered thanks to animal research apologists. Unfortunately, that means nearly all of them. So, to reiterate… 85% failure rate (“a big one”) = nearly all modern medical advances.

      “Researchers who truly want to help and develop products that work need to and do understand this issue.”

      *eye roll*

    • Juan Carlos Marvizon

      This type of “failure rate” is not something that applies only to animal research, but to human invention in general. For example, if we were to check how many of the inventions that get patented are then turned into actual devices, we will probably find “failures rates” well over 90%. How many new car designs, or plane designs, are drawn in these industries and never make it into real products? Even beyond the human realm, if we look at evolution, the vast majority of the mutations that drive it are not successful. Hence, high failure rates are an intrinsic property of innovation and invention. In fact, turning this around, I would say that a success rate of 15% or even 5% is a huge success rate.

    • Read the statement again:

      “Consider that of all the drugs which pass Phase 1 clinical trials in humans, 86% will fail in later stage human trials.”

      By your definition, human testing has an 86% failure rate.

      The reality is, it doesn’t – it misunderstands that the aim of these tests is to come out with just one or two of the best drug candidates,

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