Animal Testing: Contrary Scientific Views

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Main article: Animal Testing

The systematic reviews and meta-studies into animal testing listed below have raised serious and consistent issues with reliability, publication bias, and poor standards of conduct. Those relating to the field of psychological research are presented with an adjacent icon.

1949

[For] all practical purposes no animal has yet yielded satisfactory results.

— Review of Animal Experimentation in Infectious Hepatitis and Serum Hepatitis (1949)

2001

The methodological quality of the studies was poor… Surprisingly, we found that animal experiments and clinical studies ran simultaneously.

— Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review (2001)

2004

Much animal research into potential treatments for humans is wasted because it is poorly conducted and not evaluated through systematic reviews…Few methods exist for evaluating the clinical relevance or importance of basic animal research… The contribution of animal studies to clinical medicine requires urgent formal evaluation.

— Where is the evidence that animal research benefits humans? (2004)

2005

[Our] estimate of effect size might be too high because of factors such as study quality and possible publication bias [for animal experimentation].

— Systematic review and metaanalysis of the efficacy of FK506 in experimental stroke (2005)

2006

There seems to be a gradient of frequency of methodological weaknesses among reviews… compared to systematic reviews of human clinical trials they are apparently poorer. There is a need for rigour when reviewing animal research.

— Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research (2006)

That there is a gap between clinical research and clinical practice is well established. Our work highlights another gap — specifically the lack of communication between those involved in animal research and clinical trialists.

— Comparison of treatment effects between animal experiments and clinical trials: systematic review (2006)

2007

Poor methodological standards in animal studies mean that positive results rarely translate to the clinical domain.

— Translating animal research into clinical benefit (2007)

Discordance between animal and human studies may be due to bias or to the failure of animal models to mimic clinical disease adequately.

— Comparison of treatment effects between animal experiments and clinical trials: systematic review (2007)

In 20 reviews in which clinical utility was examined, the authors concluded that animal models were either significantly useful in contributing to the development of clinical interventions, or were substantially consistent with clinical outcomes, in only two cases, one of which was contentious [a 90% failure rate]… Animal data may not generally be assumed to be substantially useful… Possible causes include interspecies differences, the distortion of outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments…

— Systematic reviews of animal experiments demonstrate poor human clinical and toxicological utility (2007/8)

2008

Animal data may not generally be assumed to be substantially useful… Possible causes include interspecies differences, the distortion of outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments…

— Systematic reviews of animal experiments demonstrate poor human clinical and toxicological utility (2008)

2009

When a concept such as "Animal models can predict human response" is accepted as true, it is an unfounded assumption... if a modality such as animal testing or using animals to predict pathophysiology in human disease is said to be a predictive modality, then any data generated from said modality should have a very high probability of being true in humans. Animal models of disease and drug response fail this criterion.

— Are animal models predictive for humans? (2009)

One reason why animal experiments often do not translate into replications in human trials or into cancer chemoprevention is that many animal experiments are poorly designed, conducted and analysed. Another possible contribution to failure to replicate the results of animal research in humans is that reviews and summaries of evidence from animal research are methodologically inadequate.

— Why animal studies are often poor predictors of human reactions to exposure (2009)

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The predictive validity for animal models of schizophrenia has also proven difficult, particularly as predictive validity is understood in psychopharmacology – that is, a model is considered predictive if it can predict which drugs will be effective in treating the disease modeled... Similar doubts recently arose concerning the value of animal models in stroke research... no consensus exists about the order and weight of the different steps that are necessary for developing an animal model, nor are there common, generally accepted criteria for evaluating the resulting putative model.

— Evaluation of animal models of neurobehavioral disorders (2009)

2010

The largest and most comprehensive review of published animal research undertaken to date, to our knowledge, has highlighted serious omissions in the way research using animals is reported.

— Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research (2010)

Systematic reviews are generally regarded by professionals in the field of evidence-based medicine as the highest level of medical evidence…However, they are not yet widely used nor undertaken in the field of animal experimentation.

— A gold standard publication checklist to improve the quality of animal studies, to fully integrate the Three Rs, and to make systematic reviews more feasible (2010)

The value of animal experiments for predicting the effectiveness of treatment strategies in clinical trials has remained controversial, mainly because of a recurrent failure of interventions apparently promising in animal models to translate to the clinic… [this] failure may be explained in part by methodological flaws in animal studies, leading to systematic bias and thereby to inadequate data and incorrect conclusions… In fact, clinical trials are essential because animal studies do not predict with sufficient certainty what will happen in humans.

— Can animal models of disease reliably inform human studies? (2010)

[P]ublication bias is prevalent in reports of laboratory-based research in animal models of stroke, such that data from as many as one in seven experiments remain unpublished. The result of this bias is that systematic reviews of the published results of interventions in animal models of stroke overstate their efficacy… Nonpublication of data raises ethical concerns…

— Publication bias in reports of animal stroke studies leads to major overstatement of efficacy (2010)

2011

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Sadly, in spite of almost 40 years of research into depression’s mechanisms [using animals], the newest agents released onto markets today only vary from their predecessors in side-effect profile, with negligible improvements in efficacy...The overarching goal should be to narrow the gap between basic [animal] and clinical [human] fields of investigation... an important challenge of the field has been to produce a long-lasting state of depressive pathology [i.e. despair and fear] in laboratory animals, which has seldom been achieved.

— Animal Models of Depression: Molecular Perspectives (2011)

2012

Key characteristics of scientific practice, and measures to avoid bias, such as characteristics of the subject population, randomization, blinding and exclusion criteria, were infrequently reported. A number of recent systematic reviews show that this is the case in many fields of animal research.

— Ischemic Preconditioning in the Animal Kidney, a Systematic Review and Meta-Analysis (2012)

Key characteristics of scientific practice such as randomization, blinding, and description of withdrawals/dropouts are routinely published in most human clinical trials, but are often not mentioned in publications of animal studies.

— The effects of long-term omega-3 fatty acid supplementation on cognition and Alzheimer’s pathology in animal models of Alzheimer’s disease: a systematic review and meta-analysis (2012)

These deficiencies in the reporting of animal study design, which are clearly widespread, raise the concern that the reviewers of these studies could not adequately identify potential limitations in the experimental design and/or data analysis, limiting the benefit of the findings...Numerous publications have called attention to the lack of transparency in reporting, yet studies in the life sciences in general, and in animals in particular, still often lack adequate reporting on the design, conduct and analysis of the experiments.

— A call for transparent reporting to optimize the predictive value of preclinical research (2012)

2013

The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical [i.e. animal] research.

— Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments (2013)

Our review highlights a number of risk of bias assessment criteria that have been empirically tested for animal research, including randomization, concealment of allocation, blinding, and accounting for all animals.

— Instruments for Assessing Risk of Bias and Other Methodological Criteria of Published Animal Studies: A Systematic Review (2013)

Overall study quality [of animals] was modest; the median number of study quality checklist items scored was 6 (of a possible 12) and no study scored higher than 8.

— Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted? (2013)

Approximately 100 vaccines have been shown effective against an HIV-like virus in animal models, however, none has prevented HIV in humans…The success of the animal model in basic research can also be questioned based on the fact that, according to one report, only 0.004% of basic research papers in leading journals led to a new class of drugs.

— Systematic Reviews of Animal Models: Methodology versus Epistemology (2013)

2014

A very high attrition rate was found, with an overall success rate during the 2002 to 2012 period of 0.4%...

— Alzheimer’s disease drug-development pipeline: few candidates, frequent failures (2014)

Systematic review and meta-analysis has provided empirical evidence that too many preclinical experiments lack methodological rigor, and this leads to inflated treatment effects. There is of course no guarantee that improvements in the validity of preclinical animal studies and reduced publication bias will improve the translational hit of interventions from bench to bedside.

— Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically (2014)

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[R]esidual gains resulting from biomedical research were often due more to clinical research than to animal experimentation... Further, there are significant instances in which animal research delayed medical advance or misled research efforts or even led to harmful and disastrous medical interventions... the strong analogy concept of animal models is not supported in theory or practice...

— Animal models of human psychology: Critique of science, ethics, and policy (2014)

2015

The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice… animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods… of every 5,000–10,000 potential drugs investigated [through animal experiments], only about 5 proceed to Phase 1 clinical trials [a 99.9% failure rate].

— The Flaws and Human Harms of Animal Experimentation (2015)

...we underline here that there is an urgent need for improving the reporting and methodological quality of animal studies.

— A systematic review and meta-analysis of the ability of analgesic drugs to reduce metastasis in experimental cancer models (2015)

The quality of the included studies was low to moderate based on the assessment of their risk of bias. The meta-analysis showed that metformin significantly inhibited the growth of HCC tumour [but] no significant effect on the number of tumours [or] the incidence of HCC was observed...

— Anti-Tumor Effects of Metformin in Animal Models of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis (2015)

...41% of the studies did not describe the age of their animal model... A general observation in our risk of bias assessment was that the majority of the included studies did not provide sufficient information to assess the risk of bias. The studies did not adequately describe details regarding allocation of animals to the experimental groups, adjustments for baseline differences, concealment of allocation, randomization, blinding and addressing incomplete outcome data.

— Drug delivery systems for ovarian cancer treatment: a systematic review and meta-analysis of animal studies (2015)

2016

The risk of bias assessment showed that details with respect to the randomization method was not provided (Q1). It was often described that animals were randomized across different groups without describing the method of randomization, thereby limiting assessment of the adequacy of randomization and therefore the actual risk of selection bias. Another notable observation from the experimental designs studied was that only in a limited number of studies it was described that power calculations were performed, whereas sufficient power in animal experiments is a requirement for performing adequate studies.

— Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

Because of the poor reporting, the risk of many forms of bias was assessed to be unclear in most studies (Fig 2B)... In 32 studies (58%) there was an unclear risk of attrition bias, because either the number of drop-outs or the reason for exclusion was not adequately reported. In five studies (9%) there was a high risk of attrition bias since animals appeared to be missing from the analysis, but no explanation was provided. The risk of reporting bias (item 9) was assessed as unclear for all studies, since none of the studies reported the use of a study protocol predefining primary and secondary outcomes.

— Renal Perfusion and Function during Pneumoperitoneum: A Systematic Review and Meta-Analysis of Animal Studies (2016)

Of the 30 studies included in this SR, only a few applied methods to avoid bias. Five studies (17%) reported randomisation of treatment in some way. However, none of these studies mentioned the methods of randomisation applied. None of the papers stated that the experiments were blinded, described the allocation sequence or concealment during the randomisation process.

— Ibogaine and addiction in the animal model, a systematic review and meta-analysis (2016)

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[O]ur current animal models do not translate well into clinical practice... there are several obvious reasons why animal models for brain disorders are notoriously difficult. First and foremost, the brain is undoubtedly the most complex organ in our body... Another major obstacle in animal modelling is that, again in contrast to most other organs, the brain shows large species differences...

— Gene-Environment Interactions in Psychiatry: Nature, Nurture, Neuroscience, Chapter 3 ('Animal Modelling in Psychiatry') (2016)

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[T]he vast majority of neuroscience research was originally done using rats... [before] the subsequent dominant use of mice... rats and mice can show diametrically opposite responses in basic studies of cognition, addiction, impulsive and social behaviour, and demonstrate differences in extent of neurodegeneration... The translational validity of current animal models for brain diseases [to humans] has been relatively poor to date... there is an urgent need for improvement.

— Rodent models in neuroscience research: is it a rat race? (2016)

2017

There remains substantial opportunity for improvement in the reporting of animal research modelling stroke, particularly in the lacunar stroke literature.

— Risk of bias reporting in the recent animal focal cerebral ischaemia literature (2017)

References

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