Reviewed and revised 16 May 2016
- animal and laboratory studies form the lowest level of evidence for informing clinical decisions
- findings from animal and laboratory studies may be useful for determining the biological plausability of subsequent clinical studies
- they should be viewed as hypothesis generating studies only
- overall there is much commonality between human and animal biochemistry, genetics and physiology
- animal and laboratory studies may limit human suffering as a result of medical experimentation by screening out toxicities
- most of what we currently know about human biology is built upon animal research
- most the treatments currently in use involved animal and laboratory research during their development
In the basic biological sciences (from Ioannidis, 2006 and Yound et al, 2008):
- statistical considerations are secondary or nonexistent
- results entirely unpredicted by hypotheses are celebrated
- there are few formal rules for reproducibility
- a posteriori considerations that are met sceptically in clinical research, dominate
- although often never formally refuted in print, most promising preclinical work eventually fails to translate to clinical benefit
- apparently negative studies are often abandoned prematurely as wasteful
- more so than in clinical research, “good” scientists are identified by their positive results
- a lack of negative studies being published prevents meaningful systematic review
Animal studies typically suffer from these methodological problems (from Pound et al, 2004):
Disparate animal species and strains, with a variety of metabolic pathways and drug metabolites, causes variation in efficacy and toxicity
Different models for inducing illness or injury with varying similarity to the human condition
Variations in drug dosing schedules and regimen that are of uncertain relevance to the human condition
- unlike humans, animals in studies are often young, rarely have comorbidities, and are not exposed to a range of competing (and interacting) interventions
Variability in the way animals are selected for study, methods of randomisation, choice of comparison therapy (none, placebo, vehicle), and reporting of loss to follow up
Small experimental groups with inadequate power, simplistic statistical analysis that does not account for potential confounding, and failure to follow intention to treat principles
Nuances in laboratory technique that may influence results may be neither recognised nor reported—eg methods for blinding investigators
Selection of a variety of outcome measures, which may be disease surrogates or precursors and which are of uncertain relevance to the human clinical condition
Length of follow up before determination of disease outcome varies and may not correspond to disease latency in humans
References and Links
- Hackam DG. Translating animal research into clinical benefit. BMJ. 2007 Jan 27;334(7586):163-4. PubMed PMID: 17255568; PubMed Central PMCID: PMC1782020.
- Ioannidis JP. Evolution and translation of research findings: from bench to where? PLoS Clin Trials. 2006 Nov 17;1(7):e36. PubMed PMID: 17111044; PubMed Central PMCID: PMC1851723.
- Muhlhausler BS, Bloomfield FH, Gillman MW. Whole animal experiments should be more like human randomized controlled trials. PLoS Biol. 2013 Feb;11(2):e1001481. doi: 10.1371/journal.pbio.1001481. Epub 2013 Feb 12. PubMed PMID: 23424284; PubMed Central PMCID: PMC3570551.
- Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I; Reviewing Animal Trials Systematically (RATS) Group. Where is the evidence that animal research benefits humans? BMJ. 2004 Feb 28;328(7438):514-7. Review. PubMed PMID: 14988196; PubMed Central PMCID: PMC351856.
- Royal Society. The use of non-human animals in research: a guide for scientists. London: Royal Society, 2004. www.royalsoc.ac.uk/document.asp?tip=0&id=1351 (accessed 2 Mar 2013).
- Young NS, Ioannidis JP, Al-Ubaydli O. Why current publication practices may distort science. PLoS Med. 2008 Oct 7;5(10):e201. doi: 10.1371/journal.pmed.0050201. PubMed PMID: 18844432; PubMed Central PMCID: PMC2561077.