Animal and laboratory studies

Reviewed and revised 16 May 2016

OVERVIEW

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

ADVANTAGES

  • 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
  • cheaper
  • 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

DISADVANTAGES

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

Journal articles

  • 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.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

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