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 skeptically 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. PMC1782020.
- Ioannidis JP. Evolution and translation of research findings: from bench to where? PLoS Clin Trials. 2006 Nov 17;1(7):e36. 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. 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. 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
- Young NS, Ioannidis JP, Al-Ubaydli O. Why current publication practices may distort science. PLoS Med. 2008 Oct 7;5(10):e201. PMC2561077.