Limitations of animal models part 1
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Animal studies have several limitations for predicting human outcomes, including interspecies differences in disease susceptibility, pharmacokinetics, and responses to stress. Studies in stressful laboratory environments and using chronic high doses can distort results. Alternatives to animal testing are needed and should incorporate the principles of reduction, replacement, and refinement. These include addressing methodological issues in animal experiments like small sample sizes, lack of randomization and blinding, and conflicts of interest. The external validity of animal models is reduced due to differences between young, healthy research animals and elderly, comorbid human patients.
Limitations of animal models part 1
- 1. Limitations of Animal test & Alternatives Approach Animal use Part- I Dr. Kuppala Manohar Babu Professor VJ’s College of Pharmacy
- 2. Contents Limitations of Animal studies Interspecies differences Stressful environments and protocols Methodological quality Chronic high dose rodent studies Alternate approach to Animal studies Reduction Replacement Refinement
- 3. Animals do not reliably predict human outcomes, because: 1. Interspecies differences 2. Stressful environments and protocols 3. Methodological quality 4. Chronic high dose rodent studies
- 4. Alternatives of Animal use is needed because Causes: 1. Interspecies differences • Altered susceptibility to and progression of diseases • Differing absorption, tissue distribution, metabolism, and excretion of pharmaceutical agents and toxins • Differences in the toxicity and efficacy of pharmaceuticals
- 5. Causes: 2. Stressful environments and protocols Most laboratory animals spend most of their lives in small, relatively barren cages. Deleterious neuroanatomical, psychological and physiological effects Laboratory procedures Common laboratory species suffer marked stress, fear and possibly distress when subjected to: Handling Blood sampling Gavaging This stressful alteration of normal physiological parameters also predisposes to pathologies and distorts scientific results
- 6. Causes: 3. False positive results of chronic high dose rodent studies • Overwhelming of natural physiological defences such as epithelial shedding, inducible enzymes, DNA and tissue repair mechanisms, which effectively protect against many naturally occurring toxins at environmentally relevant levels • Differences in rodent physiology when compared to humans, e.g.: increased metabolic and decreased DNA repair rates • Variable, yet substantial, stresses caused by handling and restraint, and frequently stressful routes of administration, and subsequent effects on hormonal regulation, immune status and disease predisposition
- 7. Causes: 4. Poor methodological quality of animal experiments Common deficiencies are Lack of: • sample size calculations • sufficient sample sizes • randomised treatment allocation • blinded outcome assessment • conflict of interest statements
- 8. The common causes of reduced external validity of animal studies: Animals used for experiment are young and healthy, whereas in patients the disease mainly occurs in elderly people with co-morbidities. Assessment of treatment efficacy in a homogeneous group of animals vs. a heterogeneous group of patients. Insufficient similarity for inducing a disease/injury in animal models . Differences in outcome measures and assessment timing between preclinical and clinical study. POOR VALIDITY OF ANIMAL STUDIES
- 9. Alternateapproaches to Animal testing
- 13. Thank you