The ARRIVE 2.0 Guidelines: Importance and Full Adoption by AALAS Journals

Introduction

A recent editorial discussed the pending merger of the AALAS Comparative Medicine journal into the Journal of the American Association for Laboratory Animal Science (JAALAS), including the rationale supporting the decision and the March 2024 survey results that endorsed this change.³¹ In that editorial, we also briefly noted that the survey results supported full adoption of the ARRIVE (Animal Research: Reporting of In Vivo Experiments) 2.0 guidelines, and we announced that AALAS journals would fully adopt the guidelines starting on January 1, 2025. The purpose of this editorial is to document support for the full adoption of ARRIVE guidelines; provide some background on scientific reproducibility issues and the potential role of ARRIVE in addressing concerns about reproducibility, replicability, and generalizability; briefly summarize the guidelines; and describe steps to be taken to assist authors once ARRIVE guidelines are fully adopted for new manuscripts submitted starting January 1, 2025.

Support for Adoption of ARRIVE Guidelines

As part of the March 2024 survey, respondents were asked 3 questions related to adopting ARRIVE 2.0 guidelines for AALAS journals (Table 1).

The responses suggest that most respondents were aware of the ARRIVE guidelines, although question A did not capture the depth of respondent familiarity with the guidelines. We cannot be certain, but it is likely that those respondents who were aware of the guidelines (“yes” to question A, n = 153) were the ones who elected to answer questions B and C (n = 152). The responses to questions B and C suggest that an author requirement to address the ARRIVE 2.0 guidelines would not discourage manuscript submission (86.8%).

In summary, the survey results reflected broad support for the full adoption of the ARRIVE 2.0 guidelines by AALAS journals.

ARRIVE Guidelines: Background and Role in Addressing Reproducibility Issues

The ARRIVE guidelines were originally developed as a 20-item checklist in 2010 by an international working group organized by the National Centre for the Replacement Refinement and Reduction of Animals in Research (NC3Rs)²¹ and were then updated in 2020 as the ARRIVE Guidelines 2.0.^28,29 Before discussing the individual guidelines and why they are important, it is critical to understand that their development has been driven by the need for improved reporting of animal research, a factor contributing to concerns about scientific reproducibility and translation of animal research to human clinical application.^6,13,14 Emphasizing such concerns was a 2009 survey of 271 animal research articles that reported that only 59% of articles stated a hypothesis, less than 15% used randomization to assign groups or blinding to reduce observation bias, and only 70% of the publications that used statistical methods reported any measure of variability or error.¹⁴

Since then, there has been growing awareness of scientific reproducibility issues. A PubMed search using the search term “scientific reproducibility” returned 102,318 hits on July 26 of this year, encompassing all areas of science and technology, including animal research.^{5,9,15–19,32} AAALAC International notes that “programs should consider scientific rigor and experimental reproducibility when evaluating animal research activities” and cites the ARRIVE guidelines as a means to encourage both when experimental design methods are reported in peer-reviewed journals.² Some other key relevant publications addressing reproducibility (all of which reference the ARRIVE guidelines) include a 2011 publication by the U.S. National Academies,²³ 2016 reproducibility recommendations by the Federation of American Societies for Experimental Biology (FASEB),¹⁰ and a second detailed 2019 report by the U.S. National Academies.²⁰ In this 2019 publication, consensus definitions were provided for key terms:

• • Reproducibility is taken to mean computational reproducibility—obtaining consistent computational results using the same input data, computational steps, methods, code, and conditions of analysis and replicability to mean obtaining consistent results across studies aimed at answering the same scientific question, each of which has obtained its own data. In short, reproducibility involves the original data and code.

• • Replicability involves new data collection and similar methods used by previous studies.

• • Generalizability refers to the extent that the results of a study can be applied in other contexts or populations that differ from the original one.

In response to the expanded public and research community discussion of reproducibility concerns, the U.S. Congress included Section 2039, “Enhancing the Rigor and Reproducibility of Scientific Research,” in the 21st Century Cures Act passed in late 2016.¹ This section directed the NIH Director to assemble an advisory committee, which published a final report on “Enhancing Rigor, Transparency, and Translatability in Animal Research” in 2021.³ The report covers a variety of topics, and a detailed summary is beyond the scope of this manuscript, but a key recommendation was for NIH to “…improve reporting of results by setting expectations for the use of the ARRIVE 2.0 Essential 10 checklist and the inclusion of statistical measures of uncertainly and effect size.” In early 2023, NIH released Notice NOT-OD-23-057 that encouraged the use of the ARRIVE 2.0 Essential 10 checklist in all scientific reports involving NIH-supported animal research using vertebrates and cephalopods.²⁵ Note that the ARRIVE “Essential 10” items are a subset of the full ARRIVE Guidelines, which are described next.

What Are the ARRIVE Guidelines?

Simply put, the guidelines are a checklist of principles to help in all stages of animal study design and results reporting, that is, when planning, conducting, and reporting the study and for reviewers when reviewing manuscripts. An online checklist is available listing and describing the 10 items in the Essential 10 (Figure 1) plus the 11 additional items in the Recommended Set for a total of 21 items (Figure 2), as well as detailed explanations of each of the items in both checklists.²⁸

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In a sense, the ARRIVE Guidelines assist researchers with organizing and reporting the experimental details in a way that facilitates reproducibility, and it should be noted that they do not prescribe specific experimental approaches. Most of the guidelines have been required by AALAS journals for many years (Table 2), but some discussion of specific items is provided below.

Helping Authors Provide the ARRIVE Information

As shown in Table 2, of the 21 ARRIVE items, 14 are currently required. Of the 14 items currently required, 4 (items 1, 6, 7, and 9) are required but the location in the manuscript is not specified, which leads to some searching by the reviewers. In addition, the 3 items currently expected in the Materials and Methods (items 8, 15, and 16) can appear anywhere in the Materials and Methods, leading to additional searching by the reviewers.

To assist authors and reviewers, a new manuscript template will be released for use starting January 1, 2025, which will organize the manuscript so that all ARRIVE guidelines are addressed in the template. This will benefit both authors and reviewers and most likely save time for many authors because following the template helps ensure that information needed by reviewers will be present. It will also make the reviews more consistent because reviewers will not have to search for information requested by the reviewer form and all reviewers will see the information laid out in a more organized manner.

Only hypothesis-driven studies will need to use the new manuscript template. Authors of other types of manuscripts, such as case study/case series manuscripts, will be able to choose which sections and items are applicable to their data and organize the manuscript as needed.

The editors will monitor any author and reviewer concerns and make changes as needed.

Conclusions

Potential issues with respect to reproducibility, replicability, and translatability are now widely recognized in research involving animal subjects and are greatly concerning. The stakes are compounded by the waning confidence of legislative bodies and the public that science is performed ethically and carefully and that published results can be trusted. Groups intent on ending animal research have leveraged these concerns into false narratives that claim animal research is neither needed for human health nor done in an ethical manner.

These are complex problems, and there are no easy solutions. AALAS journals have consistently published relevant manuscripts on enhancing reproducibility, including a special topic emphasis on extrinsic factors affecting research divided between the March (63:2) and May (63:3) 2024 issues of JAALAS.^{4,7,8,12,30,33–35} We will always welcome new manuscripts addressing these areas.

One strategy to address all these concerns is the full adoption of the ARRIVE guidelines, which AALAS journals will do starting January 1, 2025. Use of the ARRIVE guidelines is no panacea,¹¹ but it is a step in the right direction. The 2011 NRC document noted that all stakeholders have an important role in improving reproducibility and emphasized the responsibility of journal editors to “actively promote effective and ethical research by encouraging the provision of sufficient information to enable assessment and interpretation of research findings and advancement of knowledge based on reproducible results.”²³ The editorial staff looks forward to partnering effectively with authors and reviewers to ensure that AALAS journals continue to serve our community and continue to make a strong case that animal research is critical to improving both human and animal health.