Poor Translatability of Biomedical Research Using Animals - A Narrative Review

Area of Science:

• Pharmacology and Toxicology
• Translational Medicine
• Drug Discovery

Background:

• The drug development pipeline faces a persistent failure rate exceeding 92% in translating animal test results to human treatments.
• These failures are primarily attributed to unexpected toxicity and lack of efficacy observed in human trials, which were not predicted by traditional animal models.
• This highlights a critical gap in current preclinical testing methodologies for ensuring drug safety and effectiveness.

Purpose of the Study:

• To review disease areas where animal models have historically failed to yield effective human treatments.
• To explore the potential of innovative, human-relevant new approach methodologies (NAMs) in preclinical drug testing.
• To provide recommendations for applying NAMs to improve drug safety and efficacy prediction.

Main Methods:

• Review of scientific literature and preclinical data across various disease areas.
• Analysis of the limitations of conventional animal testing in predicting human responses.
• Evaluation of emerging technologies, specifically organs-on-chips, for preclinical drug assessment.

Main Results:

• Animal models demonstrate significant limitations in predicting drug toxicity and efficacy, contributing to high failure rates in clinical translation.
• Organs-on-chips and other NAMs show superior ability in identifying potential safety issues and predicting efficacy compared to traditional animal testing.
• Evidence suggests NAMs can improve the accuracy of preclinical safety and efficacy assessments.

Conclusions:

• The high failure rate in drug translation underscores the inadequacy of animal models for predicting human responses.
• New approach methodologies, such as organs-on-chips, offer a more human-relevant and predictive alternative for preclinical drug testing.
• Adoption of NAMs is crucial for enhancing the efficiency and success rate of drug development, leading to safer and more effective human treatments.