DRIVER recommendations – About

What are the DRIVER recommendations?

In vitro models – 2D cell culture, organoids and organ-on-chip systems – are essential tools for studying biological processes and diseases. However, evidence suggests that findings using these models are not always reliable or reproducible because of the way in vitro experiments are conducted and then reported in the scientific literature. 

The DRIVER recommendations aim to improve the rigour and transparency of in vitro studies, supporting researchers throughout the entire process from study design to publication. The recommendations set out six items covering key aspects of in vitro experimentation, including the identification and mitigation of potential sources of bias, model preparation, application of procedures, data handling and reporting. Together they establish a core set of principles applicable across all in vitro models and methods.

Who are the DRIVER recommendations for?

The DRIVER recommendations have been developed for a broad range of users involved in conducting, evaluating or supporting in vitro research.

Researchers

• Promote understanding of how to conduct rigorous and reproducible in vitro experiments.
• Interactive content provides worked examples and deeper exploration of key concepts to support learning and application in practice.

Journals

• Provide a minimum reporting standard for articles reporting in vitro research.
• Highlight best practice in the design or conduct of in vitro experiments, helping editors and reviewers identify potential limitations or deviation from recommended standards.
• The guidance and interactive content support authors in using the recommendations in practice.

Funders

• Provide a framework for assessing the design of proposed in vitro studies and assessing research articles provided in support of funding applications.
• Establish clear expectations for the design, conduct and reporting of in vitro research funded.

Universities

• Support teaching and training in the design, conduct and reporting of in vitro research, with interactive content that is particularly valuable for postgraduate and early-career researchers.
• Provide a benchmark for the minimum standards expected of in vitro research conducted within the institution.

How were the DRIVER recommendations developed?

The recommendations were developed through an evidence-led, collaborative process involving an international expert working group including in vitro researchers from academia and industry, funders, journal editors, government agencies, statisticians and methodologists. 

The project initially focused on developing guidance for the reporting of in vitro research. In consultation with in vitro researchers and statisticians, the NC3Rs developed an initial draft, which was refined iteratively by the working group through expert review and prioritisation. Six key recommendations were identified and the RIVER recommendations (Reporting In Vitro Experiments Responsibly) were published as a preprint in 2023.

Feedback from researchers and stakeholders during the development and testing of the RIVER recommendations highlighted that factors affecting the reliability and reproducibility of in vitro research arise earlier in the research process during experimental design and conduct. Researchers also identified a need for practical guidance and examples to support the implementation of good practice. 

In response, the recommendations were expanded to become the DRIVER recommendations, broadening their scope from reporting to encompass both the design and reporting of in vitro studies. The DRIVER recommendations were developed into an online resource to provide supporting materials and interactive content which will be able to evolve alongside advances in in vitro models and methods.

The DRIVER recommendations and the 3Rs

In vitro studies play a key role in biomedical research, often providing early evidence for potential new treatments, compounds and biological phenomena. However, evidence suggests that the studies are often not reported with sufficient transparency to enable readers to critically appraise the methods used and appropriately interpret the results. This raises concerns about the reliability of the research and the translational value of the findings. Poorly designed or inadequately reported studies waste time, funding and other resources.

The quality of in vitro research also has important implications for efforts to reduce and replace animal use. In vitro models provide valuable alternatives to animal studies and have the potential to further decrease reliance on animals. However, concerns about the reliability and reproducibility of in vitro research, arising from shortcomings in experimental design, conduct, and reporting, can undermine confidence in these models as credible alternatives.

Failure to follow best practices in in vitro studies can also waste animals, either directly – for experiments that use tissues or reagents derived from animals – or indirectly, when unreliable findings from in vitro research inform follow up in vivo experiments. 

Building on the NC3Rs' experience in developing the ARRIVE guidelines for in vivo experiments, the DRIVER recommendations have been developed to provide an accessible starting point for improving the design, conduct, and reporting of in vitro research. The recommendations establish a set of six core principles to improve the reliability, transparency and reproducibility of in vitro research published in the scientific literature. While existing guidance on in vitro studies often focuses on specific technologies, model systems, or aspects of in vitro practice, the DRIVER recommendations provide a unifying framework of fundamental design and reporting recommendations that can be applied across the breadth of in vitro research.