The NC3Rs Releases the DRIVER Recommendations: Improving the Quality of In Vitro Research

The amazing NC3Rs has launched the DRIVER recommendations, a new framework to improve the reliability and transparency of in vitro research.

With in vitro models becoming increasingly advanced, the experiments using these models need to be designed properly, conducted consistently, and provide trustworthy data for these sophisticated models to be appropriately valued and maintain relevance to be used more prolifically throughout chemical safety assessment and drug discovery and development. DRIVER is a cross-sector framework for in vitro experimental practice not a biomedical only standard and not a substitute for industry-specific regulatory guidance.

DRIVER Recommendations Explained

The recommendations were developed by the NC3Rs in partnership with an international working group whose experience spanned academic and industry research, statistics, scientific publishing, research funding, government agencies and regulatory science. They provided guidance covering the experimental process, from designing the study and preparing the model through to conducting the experiment, analysing the data, and reporting the findings.

The framework focuses on six areas including:

• The experimental unit

• Risk of bias

• The experimental model

• Experimental procedures

• Experimental groups and exclusions

• Data availability and presentation
  

These may sound like obvious components of good science. However, evidence suggests that important information about in vitro experiments is frequently missing from published research and these data gaps can affect the interpretation of the results. It is good to see that it refers to the FAIR Principles - GO FAIR too.

The In Vitro Parallel and Differences to ARRIVE Guidelines

You may be familiar with the ARRIVE guidelines, developed to improve the reporting for research involving animals. It is important to recognize that DRIVER is not only concerned with how an experiment is reported after the work has been completed, but it is also designed to improve decisions made throughout the planning and conduct of the study. This is an important differentiator in assessing the purpose and value of DRIVER and its impact on in vitro research. The experimental unit must be understood before the statistical analysis. Inclusion and exclusion criteria should ideally be defined before the data are reviewed, not decided afterwards because a result is inconvenient or unexpected. Good reporting begins with good experimental design. This fits in with our publication on the minimum information for reporting on the TEER (trans‑epithelial/ endothelial electrical resistance) assay (Sharma et al., 2024).

DRIVER and the Impact on the Future Use of NAMs

There is considerable and justified excitement about the potential of New Approach Methodologies (NAMs) to generate more human-relevant information and reduce reliance on animal testing. But NAMs will not gain scientific or regulatory confidence because they are technically impressive or “animal-free”. They must be reliable, reproducible, address a clearly defined question and have an appropriate Content of Use (CoU).

Currently, the requirements for the justification of using a NAM are much more robust than those for continuing to use an established animal test even when evidence shows that an animal model often does not adequately predict the human outcome. If we leverage the DRIVER recommendations appropriately, we should be able to build a stronger and more consistent evidence base for the use of NAMs and other in vitro methods in place of in vivo research.

A Framework for the Wider Research Community

DRIVER is relevant to more than the scientists conducting experiments.

Journals and peer reviewers can use the recommendations as a minimum standard for evaluating in vitro research. Funders can use them to assess whether proposed studies have been designed appropriately. Universities and research organizations can incorporate the principles into training, quality systems and internal review procedures.

There is a particular value for early-career researchers. Experimental design and reporting are sometimes learned informally, with practices passed from one person or laboratory to another. A common framework, supported by practical examples, gives researchers a much clearer starting point.

The accompanying NC3Rs online resource includes interactive content, practical guidance and worked examples. This makes DRIVER something that can be used during the experiment not just for citation when the paper is being submitted.

Long-term Impact of DRIVER

The launch of DRIVER is a welcome and necessary step for the advancement of in vitro science, providing the foundation for a set of recommendations supporting reproducibility challenges. Better in vitro science does not come from technology alone. It comes from asking the right question, selecting the right model, designing the experiment properly, and being completely transparent about what was done.

Please take some time to explore the DRIVER recommendations and accompanying NC3Rs resources.

It will be interesting to see how researchers, journals and organizations begin to put them into practice.

References

https://arriveguidelines.org/arrive-guidelines https://nc3rs.org.uk/3rs-resources/driver-recommendations

Sharma M, Huber E, Arnesdotter E, Behrsing HP, Bettmann A, Brandwein D, Constant S, Date R, Deshpande A, Fabian E, Gupta A, Gutierrez R, Gutleb AC, Hargrove MM, Hollings M, Hutter V, Jarabek AM, Kaluzhny Y, Landsiedel R, Milchak L, Moyer RA, Murray JR, Page K, Patel M, Pearson SN, Petersen EJ, Reinke E, Roldan N, Roper C, Scaglione JB, Settivari RS, Stucki AO, Verstraelen S, Wallace JL, McCullough S, and Clippinger AJ (2025). Minimum information for reporting on the TEER (trans-epithelial/endothelial electrical resistance) assay (MIRTA). Archives of Toxicology 99(1):57-66. doi: 10.1007/s00204-024-03879

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