New Approach Methodologies (NAMs): What NIH’s Shift Means for Animal Research

NIH is expanding investment in human-based research methods. Here is what that means for model selection, the 3Rs, and the animal work that remains scientifically necessary.

TL;DR

NIH is building the infrastructure needed to make human-based research methods more useful and more reproducible. NAMs can replace animals for some questions, reduce animal use in others, and work alongside animal studies when whole-system biology still matters. Model selection should begin with the scientific question, the model’s context of use, and its known limits.

NIH is giving researchers more ways to study human biology

Some of the biggest developments in animal research do not involve an animal at all.

NIH announced more than $150 million in first awards through the Complement Animal Research In Experimentation (Complement-ARIE) program. The funding supports projects that develop, scale, standardize, and validate laboratory and computer-based methods that better represent human biology and reduce reliance on animal models.

Those methods include organoids, microphysiological systems such as organs-on-chips, human cell and tissue models, and computational approaches. Together, they are often called New Approach Methodologies, or NAMs.

The investment is substantial, but researchers still need to determine whether a model accurately represents the biology being studied, produces reproducible results, and provides evidence they can interpret with confidence.

The same considerations apply when selecting animal models.

What counts as a NAM?

NIH uses NAMs as a broad term for approaches that may be used alone or with other models. Examples include human-based in vitro systems, computational models, real-world data, organoids, and microphysiological systems.

An organoid is a three-dimensional cell-based model that reproduces selected features of a tissue. An organ-on-chip adds an engineered environment that may include fluid flow, mechanical forces, or interactions among cell types. Computational models examine relationships in existing data or simulate biological processes.

Each approach represents part of biology. An organoid may capture tissue organization while leaving out circulation or organ-to-organ signaling. A computational model may reveal useful patterns while remaining dependent on the data and assumptions used to build it. Those boundaries show researchers where another source of evidence may be needed.

Why NIH is investing beyond model development

A clever model in one expert laboratory is not yet a dependable research tool for everyone else.

Researchers need clear protocols, appropriate controls, well-characterized outputs, and evidence that results can be reproduced across people, laboratories, and platforms. NIH’s current guidance asks investigators to consider scientific suitability, human relevance, translatability, context of use, benefits, limitations, and reproducibility when choosing a model.

That explains why Complement-ARIE includes validation and qualification as well as development. Standardization is not the glamorous part of a new technology, but it is the part that lets another laboratory trust and use it.

For researchers, this investment should lead to more credible choices. It should also make vague claims such as “human-relevant” harder to use without explaining which human biology the model actually represents.

Are NAMs replacing animal models?

They already replace animal use in some applications, and their reach will grow as the methods mature.

Other questions still depend on interactions that occur across an intact organism. Blood pressure, for example, reflects cardiac output, vascular resistance, renal function, neural regulation, hormones, activity, and metabolism. Researchers can study parts of that system with cells, tissues, chips, and computation. A study centered on the integrated physiological outcome may still require an animal model.

NIH’s model-selection guidance leaves room for that scientific judgment. Investigators may propose a well-justified model or combination of models that fits the research aim. Some funding opportunities may call specifically for human-based science or NAMs, so researchers should always read the definition and scope of the individual opportunity.

The useful change is a larger set of choices. A project might use computational screening to narrow candidates, a human-derived system to examine mechanism, and an animal model to study systemic physiology. Another project may answer its question entirely without animals.

NAMs and the 3Rs belong in the same conversation

Replacement, Reduction, and Refinement have guided responsible animal research for decades. NAMs create additional ways to put those principles to work.

Replacement: use another model when it can answer the question

If a validated non-animal approach can produce the evidence a study needs, a live animal may not be necessary for that part of the work.

Replacement also applies to procedural training. A person learning tail vein injection or blood collection needs practice locating and accessing a small vessel. Kent Scientific’s Humaneway Mouse and Rat Tail Vein Simulators provide a reusable training model for that work before a learner moves to a live animal. The current product page states that the simulators are designed for up to 100 uses; the kit includes the simulator, injection sets, and blunt needles.

The experimental model may still be an animal. The first attempts at learning the skill do not have to be.

Reduction: collect the information the study needs with sound design

Reduction means using the appropriate number of animals, supported by study design and statistical reasoning. It does not mean making a group too small to answer the question.

Longitudinal measurements may help in some protocols because the same animal can be followed over time. Kent’s CODA noninvasive blood pressure systems use tail-cuff volume pressure recording in mice and rats and can support repeated blood pressure measurements without surgical implantation. Whether that reduces animal numbers depends on the design, endpoints, power analysis, and welfare considerations; the equipment does not guarantee a reduction by itself.

Refinement: manage the conditions that affect both welfare and data

Refinement includes training, handling, anesthesia, warming, monitoring, and recovery. These details shape the animal’s experience and can become experimental variables.

Anesthesia and temperature are good examples. Small rodents can lose heat quickly under anesthesia, and temperature drift can affect physiology and signal quality. Kent’s small-animal anesthesia and warming systems are designed to support controlled procedures in mice and rats. The right setup still depends on the species, procedure, protocol, monitoring plan, and institutional guidance.

This is where Kent’s three pillars meet in the same workflow: Animal Welfare, Workflow Efficiency, and Data Quality. A repeatable procedure can reduce avoidable variation, make training easier to standardize, and give the animal more consistent support.

What animal researchers can do now

No laboratory needs to force a NAM into a study simply because the term appears in a funding announcement. NIH’s guidance is more demanding than that.

Start with the question. Identify the biology the model must represent and the evidence the study must produce. Then examine the available models for scientific suitability, human relevance, context of use, reproducibility, and limitations.

Ask where a non-animal method can answer the whole question or one useful part of it. Look for animal-free training opportunities. If an animal model remains necessary, review the protocol for realistic opportunities to reduce and refine without weakening the study.

Kent’s practical guide to IACUC protocols offers a useful companion for documenting that reasoning. The justification should connect the research objective, model choice, alternatives considered, procedures, and endpoints.

More models should lead to more thoughtful choices

NIH’s investment in NAMs gives researchers more ways to study human biology and more pressure to explain why a particular model fits the job.

That is healthy for the science. Some questions will move fully to non-animal approaches. Some studies will combine methods. Animal models will continue to provide information when behavior, time, systemic physiology, or the animal itself is central to the research question.

The responsibility is familiar: choose the model that can answer the question, understand what it leaves out, and use animals thoughtfully when their use remains necessary.