An equal, albeit indirect, source of human suffering is the opportunity cost of avoiding promising drugs due to deceptive animal trials.68 Given that drug candidates typically go through the development pipeline and perform human tests that are largely based on positive animal results69 (i.e., positive efficacy and negative side effects), Medications are sometimes used based on unsuccessful results in animals (i.e. negative efficacy and/or positive side effects). Since much of pharmaceutical companies` preclinical data is proprietary and therefore not publicly available, it is difficult to know how many opportunities are missed due to misleading animal testing. However, out of 5,000 to 10,000 potential drugs studied, only about 5 are in Phase 1 clinical trials.70 Potential treatments may be abandoned based on the results of animal studies that do not apply to humans.71 Treatments that do not work due to species-specific influences or that have side effects in animals may be abandoned in preclinical trials. even though they have been shown to be effective and safe in humans. whether they are allowed to continue during drug development. Pipeline. On closer inspection, it`s not hard to see why animal stroke experiments can`t be successfully transferred to humans, even with new guidelines. Standard stroke medications are likely to affect different types differently. There is little evidence that a female rat, dog or monkey adequately replicates the physiology of a human female.
Perhaps most importantly, reproducing pre-existing stroke conditions in animals is just as difficult as replicating stroke pathology and outcomes. For example, most animals do not naturally develop significant atherosclerosis, which is one of the main contributors to ischemic stroke. To replicate the effects of atherosclerosis in animals, researchers pinch their blood vessels or artificially insert blood clots. However, these interventions do not replicate the sophisticated pathology of atherosclerosis and its underlying causes. The reproduction of human diseases in animals requires the reproduction of predisposing diseases, which is also a major challenge. The inability to replicate the disease in animals in a way that is relevant to human stroke has contributed to a high rate of drug development failure. More than 114 potential therapies originally tested on animals have failed human trials.26 4.See Shanks N, Greek R, Greek J. Are animal models predictive for humans? Philosophy, Ethics, and Humanities in Medicine 2009;4:2 [CMP free article] [PubMed] [Google Scholar].
See also Wall RJ, Shani M. Are animal models as good as we think? Theriogenology 2008;69:2–9. [PubMed] [Google Scholar] This type is a professional model and has never been used for animal experiments. Photo: iStock In another example of human suffering caused by animal testing, six human volunteers were injected with an immunomodulatory drug, TGN 1412, in 2006.60 Within minutes of receiving the investigational drug, all volunteers experienced a serious side effect due to a life-threatening cytokine storm resulting in catastrophic systemic organ failure. The compound was designed to cushion the immune system, but it had the opposite effect in humans. Prior to this first human study, TGN 1412 was tested on mice, rabbits, rats and NHPs with no side effects. NHPs have also been studied for repeated dose toxicity and have received 500 times the human dose for at least four consecutive weeks.61 None of the NHPs showed the negative effects that people experienced almost immediately after receiving small amounts of the drug being tested. Cynomolgus and rhesus monkeys were specifically selected because their CD28 receptors showed a similar affinity to human CD28 receptors with TGN 1412. Based on these data, it was confidently concluded that the results of these NHPs would most reliably predict drug responses in humans – a finding that proved devastating. Many laboratories that use animals are not required by law to provide veterinary care or pain relief, to consider or research alternative methods of testing, or to be inspected by the U.S. Department of Agriculture or any other agency.
The LD50 test is used to test the dose of a substance needed to induce death in 50% of non-human animal subjects within a given time.
