Efficacy Testing Mouse Models

Disease models expressing human disease genetics or human drug targets show superior translational predictivity. Humanized target expression particularly critical for biological therapeutics. Multiple complementary efficacy endpoints capturing mechanism provide better predictivity than single endpoints.

Clinical disease typically presents with existing pathology (reversal scenario) rather than prevention context. While prevention studies inform basic mechanisms, reversal studies more closely approximate clinical scenarios. Combination prevention and reversal studies provide comprehensive efficacy characterization.

Statistical power calculations accounting for expected effect size and acceptable alpha and beta error rates determine sample size. Typical studies require 8 to 12 animals per treatment group providing 80% power to detect 30 to 40% therapeutic improvements. Larger effects require fewer animals, smaller effects require more.

Exploratory efficacy studies include basic safety monitoring (body weight, clinical signs, terminal necropsy). Formal toxicology studies require dedicated protocols with additional parameters not feasible during efficacy studies. Efficacy studies reveal dose limiting toxicity guiding formal toxicology study design.

Endpoints directly relevant to human disease benefit (survival, functional improvement, symptom relief) provide strongest proof of concept. Biomarker and mechanistic endpoints supporting functional benefits strengthen proof of concept through mechanism-of-action clarity.