New Approach Methodologies (NAMs) Complement but Cannot Replace Animal Models in Critical Care Medicine Research

Area of Science:

• Critical care medicine
• Preclinical research methodologies
• Translational science

Background:

• Critical care research addresses severe conditions like sepsis and trauma, leading to significant mortality.
• New Approach Methodologies (NAMs) like organoids and organ-on-chip platforms are emerging as alternatives to animal research.
• Current policy initiatives encourage NAM adoption, prompting an evaluation of their capabilities in critical care.

Purpose of the Study:

• To assess the current capacity of NAMs to replace animal models in critical care research.
• To identify the limitations of NAMs in replicating complex, whole-organism responses.
• To propose an integrated approach for future critical care research.

Main Methods:

• Review of existing literature on NAMs and animal models in critical care.
• Analysis of critical illness complexity, including organ interactions and systemic feedback.
• Evaluation of NAMs' suitability for specific critical care research domains and organ injuries.

Main Results:

• NAMs are effective for studying isolated biological systems but cannot currently replicate integrated physiological responses seen in critical illness.
• Animal models remain indispensable for evaluating multi-organ dysfunction, therapeutic safety, and disease progression.
• Current NAM technologies are insufficient to fully replace animal models in critical care research.

Conclusions:

• A "methodological pluralism" approach, integrating NAMs with well-designed animal studies, is essential for critical care advancements.
• Harmonized endpoints and reverse-translation frameworks are needed to effectively combine NAMs and animal models.
• Strategic, fit-for-purpose deployment of both research methods will ensure scientific rigor, ethical considerations, and public health progress.