Genetic Background and Sex: Impact on Generalizability of Research Findings in Pharmacology Studies
| Autor: | David L. McKinzie, Stephanie M. McTighe, Stacey J. Sukoff Rizzo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Genetic diversity Drug discovery Disease Computational biology Biology Clinical trial 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Inbred strain Mutation (genetic algorithm) Generalizability theory 030217 neurology & neurosurgery Selection (genetic algorithm) |
| Zdroj: | Good Research Practice in Non-Clinical Pharmacology and Biomedicine ISBN: 9783030336554 |
| Popis: | Animal models consisting of inbred laboratory rodent strains have been a powerful tool for decades, helping to unravel the underpinnings of biological problems and employed to evaluate potential therapeutic treatments in drug discovery. While inbred strains demonstrate relatively reliable and predictable responses, using a single inbred strain alone or as a background to a mutation is analogous to running a clinical trial in a single individual and their identical twins. Indeed, complex etiologies drive the most common human diseases, and a single inbred strain that is a surrogate of a single genome, or data generated from a single sex, is not representative of the genetically diverse patient populations. Further, pharmacological and toxicology data generated in otherwise healthy animals may not translate to disease states where physiology, metabolism, and general health are compromised. The purpose of this chapter is to provide guidance for improving generalizability of preclinical studies by providing insight into necessary considerations for introducing systematic variation within the study design, such as genetic diversity, the use of both sexes, and selection of appropriate age and disease model. The outcome of implementing these considerations should be that reproducibility and generalizability of significant results are significantly enhanced leading to improved clinical translation. |
| Databáze: | OpenAIRE |
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