Can Animal Models Of Disease Reliably Inform Human Studies?
The use of animal studies in predicting the effectiveness of treatments in human patients is controversial because of the systematic bias and failure to report complete data in findings. Publication bias may account for up to one-third of this disparity in efficacy, according to this article.
Deficiencies in the ability of animal research to predict effective treatment strategies for humans may be due to methodological flaws in underlying animal studies leading to systematic bias and critical disparities that exist between animal models and clinical trials. For example, statistically the benefits shown in animal models may not be sufficient to predict the true benefits of the treatment. In addition, the failure of promising interventions to translate to the clinic may result from inadequate animal data. Finally, publication bias exists in unpublished negative or neutral trials, which ultimately should be considered in the overall efficacy of any treatment.
Methods to improve the internal validity of a finding should include focus on:
- Randomization
- Blinding
- Sample size calculation
- Monitoring of physiological parameters
- Eligibility criteria and drop-outs
- Statistical analysis
- Control of study conduct
- Bias in animal studies
- Quality checklists
Further, even if the design of an animal study is considered sound, to eliminate the possibility of bias, this articles says that measures must be taken to ensure the external validity of animal studies. Common causes of reduced external validity include:
- Induction of disease in young, healthy animals where in humans the disease occurs in the elderly.
- Assessment of treatment in a homogeneous group of animals versus a heterogeneous group of patients.
- The use of either male or female animals only where the condition occurs in both human genders.
- The use of models that are insufficiently similar to humans.
- Delays to start of treatment are unrealistic in clinic.
- Differences in outcome measures and timing of outcome between animal studies and clinical trials in humans.