Dear ORS Members,
As your Editor-in-Chief of our Journal of Orthopaedic Research, conflicts between ORS members over ethical use of animals for research have come to my attention and need to be addressed. In general, these conflicts are about cultural, regional, and national differences of opinion and laws pertaining to animal species, injury models, pain managements, and pain assessments, in Institutional Animal Care and Use Committee (IACUC) approved protocols. As we are an international community, these differences are to be expected. However, to adequately respect large differences, I believe the time has come to go beyond mere IACUC approval for peer reviewed publication in the JOR. Therefore, I have tasked the ORS Preclinical Models Section to produce new guidance regarding expectations of animal care, pain control, and experimental design for submissions to the JOR which involve preclinical animal models. Please review the first draft of this new guidance and post your thoughts and recommendations on this subject in the form field below. This information will be collated in January to derive a final draft of guidance that will be voted on for approval at the Preclinical Models Section meeting at the 2025 ORS Annual Meeting in February. As my intention is to incorporate the approved guidance into the JOR submission process for peer reviewed research articles, your participation in this process is critical.
I thank you in advance.
Sincerely,
Edward Schwarz, PhD
Fellow of the Orthopaedic Research Society
Editor-in-Chief, Journal of Orthopaedic Research
While this new guidance seems like reasonable information to include in addition to the ARRIVE checklist, the total amount of detail required for preclinical study manuscripts is becoming substantial in length. I suggest that this detail be allowed to be placed in an appendix or supplementary material, or as its own methodological subsection that is not considered in the manuscript’s total word count. This may encourage authors to describe their animal model details more fully, rather than having to be selective with words to fit within the overall manuscript limits.
While the requested information would be helpful to ensure animals involved in research are treated ethically, without experiencing any undue/uncontrolled pain, I believe the amount of information requested in the proposal is excessive and would take up a substantial proportion of the word limit for each manuscript. I suggest perhaps requesting a supplementary document to go with each submission in which the proposed queries are addressed instead of including them in the manuscript.
While parameters/observations/scoring for pain are now available and fairly widely used across preclinical research, the assessment of ‘discomfort’ is purely subjective. ‘Uncontrolled pain’ is also of questionable value, because in some cases, analgesia is only given in the perioperative period, and this question does not provide information as to whether rescue analgesia or humane endpoints were used in the longer term period. Perhaps stick with a link to USDA categories, make reporting of category required, and ask specifically (check box) if humane endpoints, rescue analgesia, or no additional analgesia for scientific reasons and approved by local IACUC was provided. Also, this burden of information needs to go into supplemental data. Unclear what additional info this provides in addition to a correctly filled out ARRIVE.
Requested information seems reasonable and not beyond a typical U.S. IACUC application. Agree with the comments about not counting against the submission length restriction.
I agree that this is an important issue. I think requiring authors to submit proof of IACUC approval and documentation that the ARRIVE guidelines were followed would be sufficient without adding another layer to the submission process.
I am curious how differences in opinion across different approved IACUC protocols will be reconciled here in terms of decision making. Is the idea that this is for reporting purposes or that the information will be used to determine whether a study has met some additional criteria to be considered ethical? And if there are standards that will supercede IACUC, then these need to be transparently posted and not left up to individual reviewers to decide. In my opinion, it is not the journal’s place to override approved IACUC procedures.
This is the bare minimum what should be reported in animal studies.
While i agree with all the above comments and also with the new questionaire – i would go one step further in including one question that partains to the training of animals towards the experimental procedure (to reduce stress) and another whether efforts for extra enrichment in housing was made – two questions that would be yes or no answers but would give a deep insight into the experimental set up and whether refinement is taken seriously.
I agree with above concerns about word limit. I agree with above comment about needing clarification for whether additional criterial are planned and these need to be transparent. I think some of the questions overlap with ARRIVE guidelines and some of the questions are too specific (trauma, infection, which limb/spine). I am concerned that yet another layer of documentation will simply reduce submissions and authors will go to another journal with fewer additional barriers. Has the publications committee also been part of this process?
Valid monitoring, assessments, and pain, wound/joint, and general health management need to be documented with results presented. These should address the 3 Rs, established IACUC, and ARRIVE and be applied to all species. When these are documented well, reviewers’ personal opinions and perspectives and biases should be irrelevant and should be address accordingly by the editor (or session moderator). I dont see need at all for additional requirements or documentation, I see the need for this to be done well by investigators/authors, reviewers, and editors/moderators. This is not currently the case at JOR/ORS.
Suggestion to improve transparency and minimize selective reporting– Did adverse events occur and was that data included or excluded.
Thank you for the valuable discussion at today’s PCM sessions. I appreciate that JOR is taking a leading role in setting community guidelines for appropriately reporting on animal welfare and animal pain management in published in-vivo studies. A guideline list such as this one will work to supplement what the ARRIVE/PREPARE guideline document already asks but focus on animal welfare and pain management considerations, particularly on reporting such measures systematically. I would also suggest that some of this information authors would provide may be written in a supplementary file, rather than the main manuscript, but have to be clearly referred to in the main manuscript, if character limits are a concern. Please find below some feedback on the form draft, for your consideration:
– What preclinical animal model was used? Briefly describe the justification for this model choice, including choice of species.
– Did your model include uncontrolled pain for the animal subjects? Rather ask: “What pain management measures (drugs, dosages, duration, frequency, route of administration) were used in your experiment? If no pain management measures were used, describe why this was scientifically relevant/necessary to justify the burden on the animal. Describe pain management protocols used after the intervention and if any clinical signs during the in-life period would require pain management.”
– How was discomfort monitored throughout the study period? Rather ask: “What pain and well-being monitoring measures were taken during the in-life period of the experiment (incl. monitoring frequency, parameters checked, duration of monitoring throughout in-life period, method of evaluation incl. grimace scales, parameters monitors)? Did you report on how effective your pain management plan was during your experiment (e.g. was the dosage sufficient)? If efficacy of pain management was insufficient, did you report on corrective measures?”
– Who evaluated animals for discomfort? Rather ask: “What was the training of personnel responsible for monitoring pain and well being?” This would be an entry not required to be reported in the manuscript, but relevant for reviewers to assess the validity of monitoring.
– If the model involved the limbs, was it unilateral or bilateral? Here it’s useful to report what justified the increased burden of a bilateral intervention i.e. the overall burden of the animal could be justified compared to the scientific output, bearing in mind the pain and suffering mitigation measures in place. The Reduce in the 3Rs doesn’t only mean a reduction of numbers. It also means reduction in overall animal suffering. Including more animals in a study with a lower expected burden per animal is preferable ethically to a lower number of animals with a high burden. Authors who may have chosen the latter should justify the need for this study design and, in light of their findings, state post-hoc whether this study design was in retrospect a valid one.
– Was a control used? If so, please describe (e.g. sham operated limb, separate control group, etc.): Rather ask: “What type of control was used? (sham, contralateral, control treatment)” Did the control cause a higher burden on the animal compared to the treatment (e.g. untreated IVD degeneration)? Did your burden mitigation strategy prove effective also in the control group?
– Did your model include an induced trauma event? If so, how was that traumatic event induced and controlled? Add: “Did you report on how reproducible the traumatic induction was in your study? Did you take into account trauma in your pain and suffering mitigation strategy? Was the strategy effective?
– Did the model include an induced infection? If so, was the infection controlled or treated in some way? Rather ask: “Did you report on the method of infection (incl. e.g. amount, method of inoculation, bacteria species)? Did you report on infection control measures, infection symptom treatment measures (incl. pain management), infection treatment measures?
Also add this question:
– Which basic animal needs were influenced/disturbed by the performed study procedures (Food and water intake, movement, social interaction etc.)? Did you report on mitigation strategies to reduce animal burden (e.g. for single housing, providing eye and nose contact with neighbors). Was that effective?
Salim Darwiche, PhD
University of Zürich