The Predictive Value of Non-Clinical Testing

3. Non-clinical studies: Ability to predict studies in humans

3.1. Animal Models

The use of relevant non-clinical models and animal species is key to obtain predictive data for humans. This accounts for all types of medicines and clinical trials in the medicine development process. For most new medicines, science-driven strategies are applied. This is especially true when researchers study biologics . Therefore much effort goes into selecting the test systems and animal species that are most suited to predict studies in humans.

Animal species are selected based on how similar the animal species and humans are. It depends on aspects such as:

The pharmacodynamics in the animal species should be similar to that of humans. The target, structural homology (shared ancestry), distribution, communication pathways in the cells, and the effects of the medicine should all be taken into account. Non-clinical trials should collect information on the pharmacokinetics of the drug candidate. This information will be used to calculate the first doses in early clinical trials and to predict the therapeutic doses in later trials. The calculations must be based on the result from toxicology studies and in the case of biologics, the calculations are often based on the body's response to the medicine. When researchers select an animal model, it is important that they evaluate the physiology and pathophysiology of the animal species in question against that of humans. Healthy animals have been used to predict efficacy and safety in patients. However since the patients have a disease, they also have an altered physiology. Therefore, animal models with the disease in question are now often used in non-clinical testing. Special considerations must be taken to deduct or extrapolate data from animals to special groups such as paediatric and geriatric patients, or pregnant women.

The choice of animal species also depends on practical considerations, such as how available they are and how easy they can be used in standard laboratory environments and procedures. Researchers will often do a screening test before the animal species is selected.

Some examples of animal models include:
  • Rat (osteoporosis, inflammatory diseases, diabetes, obesity, cardiovascular dysfunctions, neurodegenerative diseases, cancers).
  • Monkey (osteoporosis, inflammatory diseases).
  • Pig (cardiovascular dysfunctions such as hypertension).
  • Mouse (cancers, some genetic diseases).