Open Transparent Communication about Animals in Laboratories: Dialog for Multiple Voices and Multiple Audiences

Round 1

Reviewer 1 Report

Carbone presents a timely summary of current openness initiatives in the area of animal use in research, and provides his informed review of additional directions that he believes should be taken. In particular, he argues for additional consideration of animal protectionists' perspectives when designing openness tools: otherwise, the scientific community risks inadvertant (or purposeful) exclusion of key information that "the public" wants to have.

Carbone is well-placed to provide this type of commentary, and, frankly, the content is a breath of fresh air in a debate filled with misinformation and excessive secrecy. I believe that this is an important essay that is fully appropriate for publication.

My few concerns have to do with the presence of occasional confusing sentences, usually due to extra, missing, or misspelled words or punctuation. I flag them below. I also point out several points at the paragraph level that should be considered for revision.

1. Sometimes periods appear before the citation and sometimes after. Be consistent.
2. 1st full paragraph page 2, missing "are" I believe.
3. Final sentence of that paragraph is confusion--not sure about the point.
4. 1st full paragraph page 3: missing italics on "why".
5. Figure 1: I think this nicely captures current perspectives, but I feel that it would be important to provide the comparable figure for information flow as perceived by animal protectionists. This should be included with some text pointing out the relevance of this perspective, which can strengthen researchers' understanding of why it may be important to include protectionists in design of communication.
6. Tables: Formatting is a bit awkward. Could the points be left-justified? (Should meet journal standards).
7. 2nd paragraph, 1st sentence, page 6, should be "captured" (?).
8. 3rd paragraph that page: Is the intent to say that "protectionist" is the most appropriate word, according to the author, versus "activist"? And does this imply that "protectionist" will be used for the remainder of the essay? Please clarify the intent of this paragraph.
9. 4th full paragraph page 7, missing text at the end.
10. Final paragraph page 8: It is not clear what point the author intends to make. It would seem to me that "invitations for input" into communication design have an entirely different purpose than surveys of general public attitudes and questions. Surveys do not "advocate", but rather provide information that can be used by advocates for any viewpoint. Also, regarding the Sandgren quote, it is not clear how the author intends this information to fit into the paragraph. Is it an argument for sharing all facts regardless of "side"?
11. 3rd paragraph, page 9: Middle sentence starting "In the UK" seems to be missing a word.
12. Final paragraph that page: should it be "ignorant"?
13. 1st paragraph page 10, should there be a comma after "though"?
14. Final paragraph that page, extra word (get rid of either but or so).
15. Final paragraph page 11: text missing.

These should be easy issues to deal with.

Author Response

Reviewer #1:

Carbone presents a timely summary of current openness initiatives in the area of animal use in research, and provides his informed review of additional directions that he believes should be taken. In particular, he argues for additional consideration of animal protectionists' perspectives when designing openness tools: otherwise, the scientific community risks inadvertant (or purposeful) exclusion of key information that "the public" wants to have.

Carbone is well-placed to provide this type of commentary, and, frankly, the content is a breath of fresh air in a debate filled with misinformation and excessive secrecy. I believe that this is an important essay that is fully appropriate for publication.   Thank you

My few concerns have to do with the presence of occasional confusing sentences, usually due to extra, missing, or misspelled words or punctuation. I flag them below. I also point out several points at the paragraph level that should be considered for revision.

1. Sometimes periods appear before the citation and sometimes after. Be consistent. I believe I have ferreted out all the incorrect ones and placed the punctuation after the citation
2. 1st full paragraph page 2, missing "are" I believe. Unfortunately, I don’t find where that is necessary, and Word’s grammar check is not helping. No change made at this point. Perhaps editorial staff got this before I did.
3. Final sentence of that paragraph is confusion--not sure about the point.  I have changed that sentence (which read, The historical perspective includes decades of strategies for maintaining secrecy about animal use and outsiders’ strategies, some legal, others not, and all of them long before modern communications technologies, for breaking through that secrecy.” to “The historical perspective includes decades of scientists’ strategies for maintaining secrecy about animal use competing with outsiders’ strategies, some legal, others not. This competition that started in the days of paper continues in the days of  electronic communications technologies, where both can broadcast descriptions and images broadly, or targeted to chosen audiences.”
4. 1st full paragraph page 3: missing italics on "why". Thanks; I’ve made that change
5. Figure 1: I think this nicely captures current perspectives, but I feel that it would be important to provide the comparable figure for information flow as perceived by animal protectionists. This should be included with some text pointing out the relevance of this perspective, which can strengthen researchers' understanding of why it may be important to include protectionists in design of communication. I have done that (new: Figure 2) I have also added Figure 3, in which the overlapping circles of outsider and insider co-produce the information that the “general public” receives.
6. Tables: Formatting is a bit awkward. Could the points be left-justified? (Should meet journal standards).  These tables were reformatted by the journal’s editorial staff, so I am not changing them and will defer to the editors
7. 2nd paragraph, 1st sentence, page 6, should be "captured" (?). Sounds good; I have made that change.
8. 3rd paragraph that page: Is the intent to say that "protectionist" is the most appropriate word, according to the author, versus "activist"? And does this imply that "protectionist" will be used for the remainder of the essay? Please clarify the intent of this paragraph. I have thoroughly reworked my definitions of “activist” “advocate” and other terms
9. 4th full paragraph page 7, missing text at the end.  That sentence went away when I rewrote my coverage of ARRIVE
10. Final paragraph page 8: It is not clear what point the author intends to make. It would seem to me that "invitations for input" into communication design have an entirely different purpose than surveys of general public attitudes and questions. Surveys do not "advocate", but rather provide information that can be used by advocates for any viewpoint. Also, regarding the Sandgren quote, it is not clear how the author intends this information to fit into the paragraph. Is it an argument for sharing all facts regardless of "side"? I have rewritten this paragraph to try to be clearer. The original paragraph was: I draw a distinction between these invitations for input versus the types of public surveys and market research that can show what a general public might care about or want to know about {Sandgren, 2019 #5201;Bailey, 2018 #5297}. It is a subtle distinction, but the latter have as their goal trying to persuade, convince or garner support as opposed to telling people what they want to know simply because they said they want to know. As Sandgren, a medical research scientist who has worked to communicate with the local animal protection community in Madison, Wisconsin says: “Through my interactions with animal activists, I’ve discovered that we share several beliefs. In particular, we each feel that the public will agree with ‘our side’ if they have all the facts {Sandgren, 2014 #5257}.” My reworked version is: I draw a distinction between these invitations for input versus the types of public surveys that can show what a general public might care about with the aim of marketing a message that will persuade, convince or garner support {Sandgren, 2019 #5201;Bailey, 2018 #5297}. The distinction may be subtle, and requesting public input may serve more than one goal. Sandgren, a medical research scientist who has worked to communicate with the local animal protection community in Madison, Wisconsin tries to straddle the distinction between strategic listening with a goal of persuasion and meeting an obligation to inform outsiders about what they want to know more about. He writes: “Through my interactions with animal activists, I’ve discovered that we share several beliefs. In particular, we each feel that the public will agree with ‘our side’ if they have all the facts {Sandgren, 2014 #5257}.”
11. 3rd paragraph, page 9: Middle sentence starting "In the UK" seems to be missing a word. Thank you; I have added the word though.
12. Final paragraph that page: should it be "ignorant"? No, but I have reworked that section, and the relevant sentence is now: “Occasionally, scientists, veterinarians, caregivers or others may knowingly or unknowingly fail at their commitments to the animals.”
13. 1st paragraph page 10, should there be a comma after "though"? No, but I have changed though to although which I think helps the reader follow that sentence
14. Final paragraph that page, extra word (get rid of either but or so). I’ve replaced but and so with a ; so the sentence that contained …for this essay, but so my focus… now reads, … for this essay; my focus…
15. Final paragraph page 11: text missing.  You’re correct. I’ve broken the problematic sentence into two, and it now reads: In the 1990s, the National Antivivisection Society sued NIH to ban the use of the mouse ascites method to produce monoclonal antibodies. In response, the National Academy of Sciences included a representative of the HSUS onto a panel with scientists and veterinarians to review possible replacements and refinements; that use of mice is now mostly obsolete.    The last sentence in that paragraph trailed off so I have replaced Animal welfare standards should combine the best available knowledge with sound values and ethics, and I propose that any professional groups that put forth welfare recommendations would do well to invite representation of welfare advocates for the most robust review of the ethics and with Animal welfare standards should combine the best available facts with sound values and ethics, and I propose that any veterinary or scientific groups that put forth welfare recommendations would do well to invite representation of knowledgeable welfare advocates and protectionists.

These should be easy issues to deal with.  Yes, thanks.

Author Response File: Author Response.docx

Reviewer 2 Report

 

This well-written, urgent, and creative paper offers up potential pathways of communication between researchers involved with what might be described as animal dependent science, and those concerned with refining or eliminating harm-producing research methods that use animals. The author is right to point out that such interactions, both within the scientific community, and with those who are outside but actively concerned, and other members of the public only casually interested, are particularly absent or minimized in the United States, where animal use appears to be growing. 

 

The author is an example of the kind of professional, equipped by training and experience, to make these suggestions with credibility. The author identifies the UK’s Concordat initiative as an example of a hopefully sincere attempt to broaden communication between scientists and long entrenched British protection groups.  I agree that instantiating the ground work for a  “new openness” requires commitments from researchers similar to those found in the Concordat:

  

We will be clear about how, when and why we use animals in research; We will enhance our communication with the media and the public about our research using animals; We will be proactive in providing opportunities for the public to find out about research using animals; We will report our progress annually and share our experiences.    

 

My only suggestion is that the author consider discussing the distinction between Communicative Action and Instrumental Action described by the philosopher Jurgan Habermas in his classic Theory of Communicative Action.  In this theory a distinction is emphasized between attempts to manipulate a listener as opposed attempting to deepen the listener’s understanding of the speakers position/beliefs.  In my view, the majority of interactions between the different groups involve manipulation and not understanding

End of page 11 - something missing?

Author Response

Reviewer #2:

 

This well-written, urgent, and creative paper offers up potential pathways of communication between researchers involved with what might be described as animal dependent science, and those concerned with refining or eliminating harm-producing research methods that use animals. The author is right to point out that such interactions, both within the scientific community, and with those who are outside but actively concerned, and other members of the public only casually interested, are particularly absent or minimized in the United States, where animal use appears to be growing. 

The author is an example of the kind of professional, equipped by training and experience, to make these suggestions with credibility.   Thank you   The author identifies the UK’s Concordat initiative as an example of a hopefully sincere attempt to broaden communication between scientists and long entrenched British protection groups.  I agree that instantiating the ground work for a  “new openness” requires commitments from researchers similar to those found in the Concordat: 

We will be clear about how, when and why we use animals in research; We will enhance our communication with the media and the public about our research using animals; We will be proactive in providing opportunities for the public to find out about research using animals; We will report our progress annually and share our experiences.    

My only suggestion is that the author consider discussing the distinction between Communicative Action and Instrumental Action described by the philosopher Jurgan Habermas in his classic Theory of Communicative Action.  In this theory a distinction is emphasized between attempts to manipulate a listener as opposed attempting to deepen the listener’s understanding of the speakers position/beliefs.  In my view, the majority of interactions between the different groups involve manipulation and not understanding 

Thank you for this suggestion --- after I submitted the manuscript I’d made myself a note to add this insight, as Gluck and Kubacki describe it in their paper that I cite in this manuscript.

End of page 11 - something missing?  .   You are correct.  The last sentence in that paragraph trailed off so I have replaced “Animal welfare standards should combine the best available knowledge with sound values and ethics, and I propose that any professional groups that put forth welfare recommendations would …” with “Animal welfare standards should combine the best available facts with sound values and ethics, though it can be easy for those of us rooted in sciences to think we can move from animal welfare data to animal welfare standards in an objective value-neutral way, continuing an ideology that science and data can exist in a value-free vacuum”

Reviewer 3 Report

This commentary article is a thought-provoking essay, which makes some good points about the need for greater openness in animal research and what would constitute full openness. It argues for sharing of unbiased information about animal use and care, and makes some suggestions for improvement, particularly aimed at the USA. It also calls for dialogue with the public so that what is shared is what they would wish to know. The piece is informed by the personal experience of the author working as a laboratory animal veterinarian. Most of his points seem reasonable, but there are some issues within the manuscript that should be addressed.

Repeated references are made to the UK situation (which, it is acknowledged, is more advanced in terms of openness on animal research), and UK organisations and initiatives, but these are not always accurate.

Similarly, in parts it would be appropriate to acknowledge that some of what the author is calling for already takes place.

It would be helpful in places to exercise greater care in whether the point applies generally or is specific to the USA.

The negative comments about the ARRIVE guidelines don’t seem consistent with the authors call for greater openness.

 

Simple Summary and throughout

The term “animal welfare advocates” or “animal advocates” is used repeatedly in the manuscript. What is meant by this term needs to be better defined. Does it include members of anti-vivisection organisations, animal rights activists, or protesters, in addition to animal welfare organisations, for example? The distinction is an important one given it is suggested they should be invited onto ethics committees etc. and that openness initiatives should satisfy their concerns.

Abstract

“refinement-focused animal advocates deserve enhanced avenues of openness and inclusion which research advocates would fear giving”

This needs to be more nuanced, e.g. “which some research advocates” or “which research advocates may” since such advocates are already included in the work of some research organisations (e.g. serving on ethics committees; touring laboratories and advising on welfare; participating in working groups), at least in the UK.  

which a minimally interested “lay public” may not want or need.

More care needs to be taken in characterising the public view here. What evidence is there that the public are "minimally interested"? Note the latest UK poll on 'public attitudes to animal research in 2018' found that interest in finding out more about work to improve the welfare of animals in research is high (around 60%) and has risen. Whilst the proportion of the public who are not concerned at all about the use of animals in research had fallen to 15 per cent, from 22 per cent in 2016. https://www.ipsos.com/ipsos-mori/en-uk/public-attitudes-animal-research-2018

not just invite inquiry from animal advocates but to bring them in as witnesses and participants,

It should be acknowledged that this is already done in the UK and some countries; e.g. UK AWERBs commonly include staff from the RSPCA, UFAW, NC3Rs.

1. Introduction

In the past decade, with the UK’s Concordat on Openness in Animal Research at the forefront, some scientists and research institutions are trying to move past a “state of siege” to a greater friendlier invitation to a general public to “come see our [animal research] world [1-4].”

It is important to note in the manuscript that the UK Concordat was developed in response to declining public support for animal research (perhaps in response to the high level of anti-vivisection protest and animal rights activity) – see the repeated MORI polls as evidence of this. It would perhaps also be worth commenting on whether the greater openness shown by some of the signatories has led to an increase in public support for animal research.

The UK also has bodies, in particular the government supported National Centre for the Three Rs (NC3Rs, those 3 Rs being the Reduction, Refinement and Replacement efforts that Russell and Burch elaborated in the 1950s) and the private charity, the Royal Society for the Prevention of Cruelty to Animals (RSPCA), who have greater access to collaborate and communicate with the research community than US organizations currently do [12-14].

The NC3Rs and RSPCA are two very different organisations and care should be taken to separate the two here. The NC3Rs is part of the research community (officially part of UKRI; funded by the research community; itself a funder of research, including in vivo research) – this should be reflected here if reference is to be made to the NC3Rs. Whilst it does a great deal to support improvements in animal welfare and greater openness in animal research, the bar for researchers to work with NC3Rs staff is much lower for the RSPCA, which can be viewed as outsiders. The NC3Rs is, in effect, dedicated and expert, government-funded 3Rs support for the UK research community (including individual institutions, via its Regional Programme Managers).

On the other hand, while violence and vandalism were never as common in the US as in the UK,

To avoid any confusion with the organisations above, I suggest amending this sentence to make clear who were the perpetrators of the violence and vandalism, e.g. “violence and vandalism from animal rights activists”. Otherwise the juxtaposition of the two sentences could cause misunderstanding.

What I call the “new openness,” with the Concordat at its leading edge, builds on this history.

Whilst the UK may have been the first, it is important to acknowledge early on somewhere in the manuscript that there are parallel openness initiatives in other EU countries - e.g. Belgium, Portugal, Spain. You could cite this study as evidence of increased openness due to transparency agreements: https://www.eara.eu/post/eu-biomedical-sector-still-at-an-unsatisfactory-level-of-openness-about-animal-research-eara-webs

2. Full Transparency and Complete Openness are not possible

A one-way email message, like a scientific manuscript, press release, television show, or a lab’s web page, may be informative, but if it is not invitational, inviting questions and even comments, does it count as openness [7, 30]?

It needs to be acknowledged somewhere that dialogue (or steps toward it) already exist at some institutions (at least in the UK) through, for example, schools visits, the ‘I am a scientist; get me out of here’ programme https://imascientist.org.uk/, Pint of Science https://pintofscience.co.uk/, interviews from journalists, radio programmes…“ UAR annual openness reports would give some evidence of this.

My own life story

Would it be better to say “My own work history”?

My personal story well illustrates differences between the US and UK systems, with their contrasting approaches to regulatory oversight and data availability [30]. Thus, in this essay I look to the UK developments as possible precursors of changes that may come to the United States.

The aforementioned EARA report and the UAR Openness Concordat reports may be useful to cite as examples of positive change

3. Who: Insiders, Outsiders, and the “General Public”

Table 1: Public relations and tour-leaders

Shouldn’t press officers be included in the table? They’re important gatekeepers on openness in animal research.

“The public” includes negligent pet owners, vegan donors to PETA, veterinarians and physicians in community practices, and millions of people who never give much thought to animals in general or in laboratories.

Where would the author include scientists who do not work with animals? Suggest they should be mentioned here.

The RSPCA in the UK comes closer to the access necessary for this role than most organizations

One might also include UFAW here.

But where do protectionists fit in the new openness initiatives?

The Danish pharmaceutical company Novo Nordisk had a long-standing collaboration with the Danish Animal Welfare Society to develop new and higher animal welfare standards than the legal minimum. This would be a nice example to cite and would complement the references to the RSPCA (I note they inputted into the manuscript).

https://www.researchgate.net/publication/236197540_New_Housing_Conditions_Improving_the_Welfare_of_Experimental_Animals

https://www.novonordisk.com/content/dam/nncorp/global/en/science-and-technology/pdfs/bioethics/Bioethics_Animal%20research%20UK_Dec%202015.pdf

4. Animal protectionists, the status quo secrecy, and the New Openness

A century later, the NC3Rs launched its ARRIVE guidelines for increased and more transparent reporting of animals use in scientific manuscripts, aiming to improve animals’ lives indirectly, by increasing the reproducibility and quality of science [5, 6].

Improving the lives of animals is not the main aim of ARRIVE, it’s minimising wastage; so this sentence should be amended. The guidelines aim to ensure that animal studies are reported in sufficient detail to add to the knowledge base and avoid wastage of animals. Reporting in accordance with ARRIVE enables readers and reviewers to scrutinize the research adequately, evaluate its methodological rigour, and reproduce the methods or findings, maximising its value for informing future scientific studies and policy.

If referring to the launch of the ARRIVE guidelines, then the original 2010 guidelines should be cited (Kilkenny et al. 2010).

Their revised checklist contains far too many items (I count close to 40) to fit into any one manuscript, leaving scientists and journals still with the need to edit down to the partial information that seems most important for a particular paper.

This comment needs to be justified; which items specifically does the author think are not relevant, given the aims of ARRIVE?

The comment doesn’t seem fair or informed given the international expert working group reorganized the ARRIVE guidelines items into the essential 10 and recommended set precisely to facilitate their use in practice. All the major scientific stakeholders endorse use of ARRIVE, including NIH and NSF in the USA. There are plenty papers that are ARRIVE complaint, and editors and reviewers for some journals check for this as part of the review process. This negativity towards ARRIVE seems inconsistent with the authors desire and call for greater openness and improved use of animals.

But, does that mean the information that is most important to allow critique and replication of the experiments, or to document animal welfare issues that may or may not affect data outcomes [43, 44]?

It is not clear why there should ever be a choice between reporting information pertaining to the evaluation of the science, and reporting information pertaining to the way experimental subjects were treated. This dichotomy seems arbitrary; both are crucial parts of a scientific publication.

The sentence also needs re-reading as it doesn’t quite make sense.

Authors and editors alone control what information to include or to edit out, and there are no easy invitational ways to ask for what the reader thinks is important.

I have never received an author’s ARRIVE checklist.

Doesn’t seem relevant to include. Not all journals use the checklists.

posting these checklists alongside the on-line manuscript as supplementary materials would allow concerned readers

The sentence ends prematurely.

Note that publishing ARRIVE checklists alongside manuscript would certainly help peer-reviewers and readers to identify relevant information more quickly, but the checklist only indicates where in the manuscript this information can be found; it does not negate the need to include the information in the paper.

5. Toward invitational openness, in the US context: Some proposals

Bad things happen to animals in laboratories. Sometimes, this is large or small non-compliance with regulations or approved protocols, the subject of exposés, self-reports to regulators, or government inspections.

Surely it's worth including here the suffering caused as part of licensed/approved projects (which can be severe) aside from any non-compliance issues where limits on suffering are exceeded – isn't the former the greater part?

In the UK, the Home Office aggregates a year’s worth of institutional self-reports individual reports remain out of view [51, 54, 55].

The sentence structure needs improving.

Also, it would seem appropriate to mention here that in the UK non-technical summaries of project licences (approved animal projects) are published retrospectively by the Home Office, in a set format including information on the predicated harms and how the 3Rs will be applied. This is a mandatory requirement of the ASPA. https://www.gov.uk/guidance/research-and-testing-using-animals#non-technical-summaries This occurs in other countries in Europe too.

have dealt with various laboratory non compliances over 40 years, stemming from neglect or ignorance over-exuberance

Insert "or” before “over-exuberance”

This has been far overshadowed by approved activities, whether welfare compromises in the way animals are housed or the pain, injury and illness that modelling diseases entails.

The intention with this sentence is not clear - does it mean to convey that the scale of animal suffering is larger for approved activities?

In the UK, the Concordat, giving credit to input from the RSPCA, has recognized a need to communicate the harms to laboratory animals and in its annual self-review, has identified a need for more of its signatories to do more on this front [4, 36, 56]

Many organisations on the Concordat steering group stressed the need for it to include a requirement to share information on the harms caused to animals, not just the RSPCA. I suggest “RSPCA” is deleted.

Implanted metal rods

Seems odd wording and unscientific. Would “implanted head fixation devices and recording chambers” be better?

This proposal moves openness from the expanded posted information that characterizes Concordat membership to a right for open access to information and an obligation to work with the institutions' veterinarians and scientists to co-produce best practices.

It is worth recognising here or somewhere within the manuscript that proponents of openness and animal welfare advocates exist within the research community too and have been effective in influencing their peers. To acknowledge this would likely mean the article is received more positively by researchers.

Animal welfare standards should combine the best available knowledge with sound values and ethics, and I propose that any professional groups that put forth welfare recommendations would do well to invite representation of welfare advocates for the most robust review of the ethics and

The sentence ends prematurely.

References

The formatting of the references needs checking to ensure they fit the journal style.

National Centre for the Replacement, R.a.R.o.A.i.R.N.R. The NC3Rs: Pioneering better science. 2020 [cited 2020 December 22]; Available from: https://www.nc3rs.org.uk.

The full name of the NC3Rs should be used here.

 

Author Response

Reviewer #3

This commentary article is a thought-provoking essay, which makes some good points about the need for greater openness in animal research and what would constitute full openness. It argues for sharing of unbiased information about animal use and care, and makes some suggestions for improvement, particularly aimed at the USA. It also calls for dialogue with the public so that what is shared is what they would wish to know. The piece is informed by the personal experience of the author working as a laboratory animal veterinarian. Most of his points seem reasonable, Thank you  but there are some issues within the manuscript that should be addressed.

Repeated references are made to the UK situation (which, it is acknowledged, is more advanced in terms of openness on animal research), and UK organisations and initiatives, but these are not always accurate.

And thank you for pointing out the places where I’ve got inaccuracies. I think you get what I’m trying to do, looking at what’s happening in other countries mainly as a springboard to thinking about what the approach could and should be in the US., not to offer an exhaustive review of efforts in Europe or  This is certainly not the place to do a thorough description of other countries’ practices, so I’ve used your comments to help me decide what details I need to add, what to change.

A challenge here is that there is almost nothing in academic peer-reviewed literature that full lays out and analyzes openness initiatives in UK and EU (there’s a recent article by MacArthur Clark, but little of what this reviewer goes on to itemize is in that article).

Similarly, in parts it would be appropriate to acknowledge that some of what the author is calling for already takes place. Good point, and thank you for the specific points you make below that helped me in that.

It would be helpful in places to exercise greater care in whether the point applies generally or is specific to the USA. Agreed

The negative comments about the ARRIVE guidelines don’t seem consistent with the authors call for greater openness.  I discuss this more fully below, in context of where I discuss ARRIVE. I’m a big fan of ARRIVE, but my concerns are that people can think ARRIVE gives them 100% full information, which I describe as an impossibility. As it’s impossible, that raises questions of who decides what’s important enough to describe and whether outsiders [on this case, anyone not directly involved with that manuscript’s writing, editing, reviewing or publishing] can get the information they want.]  One of so many examples: someone might want to know whether veterinarians or researchers did the surgeries and pain evaluations, but author/editor/reviewers agree (as would I) that that’s not a relevant detail for most articles. 

 

Simple Summary and throughout

The term “animal welfare advocates” or “animal advocates” is used repeatedly in the manuscript. What is meant by this term needs to be better defined. Does it include members of anti-vivisection organisations, animal rights activists, or protesters, in addition to animal welfare organisations, for example? The distinction is an important one given it is suggested they should be invited onto ethics committees etc. and that openness initiatives should satisfy their concerns. Yes. I’ve added text on pages 5-6 of the uploaded manuscript to define terms as I use them, including: Insiders, Outsiders, Animal welfare advocates, Animal activists, Animal protectionists, Research advocates, Regulators, the Public.  I believe I stay consistent in my use of these terms in the revised manuscript.

Abstract

“refinement-focused animal advocates deserve enhanced avenues of openness and inclusion which research advocates would fear giving”

This needs to be more nuanced, e.g. “which some research advocates” or “which research advocates may” since such advocates are already included in the work of some research  organisations (e.g. serving on ethics committees; touring laboratories and advising on welfare; participating in working groups), at least in the UK.   Good point. Not so much the case in the US, but still, it’s a generic prediction about large numbers of people, so I am backing off my appearance of certainty that implies all would feel that way (i.e., I added the word some and changed would to might.

which a minimally interested “lay public” may not want or need.

More care needs to be taken in characterising the public view here. What evidence is there that the public are "minimally interested"? Note the latest UK poll on 'public attitudes to animal research in 2018' found that interest in finding out more about work to improve the welfare of animals in research is high (around 60%) and has risen. Whilst the proportion of the public who are not concerned at all about the use of animals in research had fallen to 15 per cent, from 22 per cent in 2016. https://www.ipsos.com/ipsos-mori/en-uk/public-attitudes-animal-research-2018  I’ve removed reference to “minimally interested” and now have a fuller description of the range of people comprising “the Public” : “For present purposes the public includes anyone not actively involved in animal research issues, even if they hold membership in an organization that does some research advocacy or funding (such as the American Medical Association or the March of Dimes) or an animal protection organization, (such as People for the Ethical Treatment of Animals or a local SPCA). Most journalists are the Public if they are writing about, as opposed to writing for or against, animals in laboratories.”

not just invite inquiry from animal advocates but to bring them in as witnesses and participants,

It should be acknowledged that this is already done in the UK and some countries; e.g. UK AWERBs commonly include staff from the RSPCA, UFAW, NC3Rs.  It would be nice to have something I can cite to support that, but later in the paper I list many examples of collaborations of researchers with outside experts such as at the RSPCA

1. Introduction

In the past decade, with the UK’s Concordat on Openness in Animal Research at the forefront, some scientists and research institutions are trying to move past a “state of siege” to a greater friendlier invitation to a general public to “come see our [animal research] world [1-4].”

It is important to note in the manuscript that the UK Concordat was developed in response to declining public support for animal research (perhaps in response to the high level of anti-vivisection protest and animal rights activity) – see the repeated MORI polls as evidence of this. I do actually state this later in the article, a few paragraphs on.

It would perhaps also be worth commenting on whether the greater openness shown by some of the signatories has led to an increase in public support for animal research. I do not believe that that cause-and-effect has been demonstrated, and indeed that would be a hard thing to establish. Certainly formation of the Concordat has not been followed by ongoing decreases in public support.  I’ve made no change in response to this suggestion

The UK also has bodies, in particular the government supported National Centre for the Three Rs (NC3Rs, those 3 Rs being the Reduction, Refinement and Replacement efforts that Russell and Burch elaborated in the 1950s) and the private charity, the Royal Society for the Prevention of Cruelty to Animals (RSPCA), who have greater access to collaborate and communicate with the research community than US organizations currently do [12-14].

The NC3Rs and RSPCA are two very different organisations and care should be taken to separate the two here. The NC3Rs is part of the research community (officially part of UKRI; funded by the research community; itself a funder of research, including in vivo research) – this should be reflected here if reference is to be made to the NC3Rs. Whilst it does a great deal to support improvements in animal welfare and greater openness in animal research, the bar for researchers to work with NC3Rs staff is much lower for the RSPCA, which can be viewed as outsiders. The NC3Rs is, in effect, dedicated and expert, government-funded 3Rs support for the UK research community (including individual institutions, via its Regional Programme Managers).  I’ve removed reference to the NC3Rs from this paragraph. I have added reference to Univ Federation for Animal Welfare (UFAW) as another charity with close ties and access to scientists/research institutes.

On the other hand, while violence and vandalism were never as common in the US as in the UK,

To avoid any confusion with the organisations above, I suggest amending this sentence to make clear who were the perpetrators of the violence and vandalism, e.g. “violence and vandalism from animal rights activists”. Otherwise the juxtaposition of the two sentences could cause misunderstanding.  Good point. I’ve separated this into a separate paragraph and specified that the violence and vandalism are animal activist violence and vandalism.

What I call the “new openness,” with the Concordat at its leading edge, builds on this history.

Whilst the UK may have been the first, it is important to acknowledge early on somewhere in the manuscript that there are parallel openness initiatives in other EU countries - e.g. Belgium, Portugal, Spain. You could cite this study as evidence of increased openness due to transparency agreements: https://www.eara.eu/post/eu-biomedical-sector-still-at-an-unsatisfactory-level-of-openness-about-animal-research-eara-websi    I have now done this; in the 2^nd paragraph of the Intro I introduce the EARA with a citation to Transparency Agreements in Spain, Portugal and Belgium.  Thanks for the link.

 

2. Full Transparency and Complete Openness are not possible

A one-way email message, like a scientific manuscript, press release, television show, or a lab’s web page, may be informative, but if it is not invitational, inviting questions and even comments, does it count as openness [7, 30]?

It needs to be acknowledged somewhere that dialogue (or steps toward it) already exist at some institutions (at least in the UK) through, for example, schools visits, the ‘I am a scientist; get me out of here’ programme https://imascientist.org.uk/, Pint of Science https://pintofscience.co.uk/, interviews from journalists, radio programmes…“ UAR annual openness reports would give some evidence of this.  I have added some sentences about live events that allow audiences to decide what questions they ask, along with the recognition that in most of these, the presenter still retains control of the answers.  It now reads: “Tours, classroom visits and some innovative media have been staples of openness efforts through the years; the Concordat encourages limited facility access to media and public, but does not require it [2]. Live interactions (of course, live via the internet in the era of COVID) offer a greater chance for information-receivers to ask the questions that are important to them, or to see things that they prioritize.”

My own life story

Would it be better to say “My own work history”?  Sure. Made that change.

My personal story well illustrates differences between the US and UK systems, with their contrasting approaches to regulatory oversight and data availability [30]. Thus, in this essay I look to the UK developments as possible precursors of changes that may come to the United States.

The aforementioned EARA report and the UAR Openness Concordat reports may be useful to cite as examples of positive change   Yes, thanks for the EARA resources. Rather then simply cite the Ormandy article here as in my first draft, I’m also citing MacArthur Clarke and the Concordat (already cited in the first draft) and adding a reference to the EARA. “My personal story well illustrates differences between the US and European systems, with their contrasting approaches to regulatory oversight and data availability [refs]. Thus, in this essay I look to other countries’ developments as possible harbingers of changes that may come to the United States.”

3. Who: Insiders, Outsiders, and the “General Public”

Table 1: Public relations and tour-leaders

Shouldn’t press officers be included in the table? They’re important gatekeepers on openness in animal research.  In the US, press officers are commonly titled Public Relations, but I have added Press Officer in hopes that will make things clearer for a non-US audience

“The public” includes negligent pet owners, vegan donors to PETA, veterinarians and physicians in community practices, and millions of people who never give much thought to animals in general or in laboratories.

Where would the author include scientists who do not work with animals? Suggest they should be mentioned here.  Great. In addition to “Institutional non-animal staff” which I am keeping from my first draft, I am adding: “Faculty scholars (including scientists who do not use animals)” and another line, “Doctors and allied clinical practitioners”  In an earlier section, I’ve made it clearer that professors and students and staff at an institution that uses animals may still be animal research “outsiders”

 

The RSPCA in the UK comes closer to the access necessary for this role than most organizations

One might also include UFAW here. I have added UFAW.

My reason to shy away from UFAW was that it inspired a US organization decades ago called Scientists Center for Animal Welfare that for a while emulated UFAW, with conferences leading to quite useful proceedings books and guidance documents, but then strayed from that mission. UFAW does seem to have kept its identity and mission more consistent (as seen from across an ocean) --- I’ve avoided going down the rabbit hole of lamenting how SCAW and some other American groups have moved away from openness over the years.

But where do protectionists fit in the new openness initiatives?

The Danish pharmaceutical company Novo Nordisk had a long-standing collaboration with the Danish Animal Welfare Society to develop new and higher animal welfare standards than the legal minimum. This would be a nice example to cite and would complement the references to the RSPCA (I note they inputted into the manuscript). 

https://www.researchgate.net/publication/236197540_New_Housing_Conditions_Improving_the_Welfare_of_Experimental_Animals

https://www.novonordisk.com/content/dam/nncorp/global/en/science-and-technology/pdfs/bioethics/Bioethics_Animal%20research%20UK_Dec%202015.pdf

Excellent --- later in the manuscript, I now list several instances of researcher/protectionist collaboration, and have added the housing conditions article to that section.

 

4. Animal protectionists, the status quo secrecy, and the New Openness

A century later, the NC3Rs launched its ARRIVE guidelines for increased and more transparent reporting of animals use in scientific manuscripts, aiming to improve animals’ lives indirectly, by increasing the reproducibility and quality of science [5, 6].

Improving the lives of animals is not the main aim of ARRIVE, it’s minimising wastage; so this sentence should be amended. The guidelines aim to ensure that animal studies are reported in sufficient detail to add to the knowledge base and avoid wastage of animals. Reporting in accordance with ARRIVE enables readers and reviewers to scrutinize the research adequately, evaluate its methodological rigour, and reproduce the methods or findings, maximising its value for informing future scientific studies and policy.

I reluctantly agree. ARRIVE, though birthed within the NC3Rs, downplays its own welfare potential (unfortunate, given how the 3Rs come from Russell and Burch’s work on humane advances). I’ve rewritten the sentence, without losing the prospect that ARRIVE can enhance animal welfare:  “A century later, the National Centre for the 3Rs (NC3Rs) launched its ARRIVE guidelines for increased and more transparent reporting of animals use in scientific manuscripts (as well as the potential to improve laboratory animal welfare).” 

If referring to the launch of the ARRIVE guidelines, then the original 2010 guidelines should be cited (Kilkenny et al. 2010).  I have added the Kilkenny, plus the 2009 survey (Kilkenny et al) that informed the first ARRIVE

Their revised checklist contains far too many items (I count close to 40) to fit into any one manuscript, leaving scientists and journals still with the need to edit down to the partial information that seems most important for a particular paper.

This comment needs to be justified; which items specifically does the author think are not relevant, given the aims of ARRIVE?    My point is that is impossible to include all details, and some are more important than others (that’s why it took a large panel of experts to develop the first and second ARRIVE versions). Consider #8, “Experimental animals.” in concert with #15 “Housing and husbandry.”  Even without considering welfare, there are so many factors that sometimes can influence research outcomes, and some are better documented as affecting outcomes than others: litter size; method of drinking water delivery; season of the year; cross-fostering; which strain’s mitochondrial DNA does an F1 animal carry; position of cage on rack; number and turnover of weekday-weekend caregivers; nearby construction projects; assurance that no late-night grad student disrupts light-cycle; how facility transitions 2x a year to daylight savings light-cycles; exclusion of hallway lighting from housing room; position in uterus; cage-size and cage-density; trio versus pair versus single-mother housing; changes in number of mice per cage as study progresses and animals reach endpoint; male versus female care staff and researchers; whether behavior testing is done in the same room as housing or cages are moved to a testing room; the microbiome “fingerprint” of gut and skin of the animals; etc.  

So, I stick to my claim that it is impossible to include every item on the checklist AND that there are items of relevance to some studies not on the checklist, but for this manuscript, I’ve reworked things to now state:  “ARRIVE faces the same challenges of all descriptive writing: “fully” reported descriptions are impossible [29]. The checklist contains far too many items (I count close to 40, and most of these have numerous subitems) to fit into any one manuscript.  Scientists and journals still need to edit down to the partial information that seems most important for scientific critique or replication. For example, item #8a, Experimental Animals, includes species, sex, strain, age/developmental stage and weight. Not only might some of those have minor relevance for certain studies, but some unlisted factors such as litter size, number of females rearing the litter, which strain’s mitochondrial DNA a hybrid animal carries or the microbiome profiles of the animals, might be highly salient for some other studies.”

 

The comment doesn’t seem fair or informed given the international expert working group reorganized the ARRIVE guidelines items into the essential 10 and recommended set precisely to facilitate their use in practice. All the major scientific stakeholders endorse use of ARRIVE, including NIH and NSF in the USA. There are plenty papers that are ARRIVE complaint, and editors and reviewers for some journals check for this as part of the review process. This negativity towards ARRIVE seems inconsistent with the authors desire and call for greater openness and improved use of animals.

You’ve pushed me to really re-examine this; thank you. I do disagree, and stand by my analysis. This is a challenge as an outsider reading the major paper describing ARRIVE 2.0 (In Percie du Sert et al, 2019) --- they state that of 31 suggested new items (microbiome, perhaps?), none met their threshold of 10% of participants agreeing on including them; unfortunately, they do not give a list of those items, but those would be perfect examples of items that some people expert enough to be on the ARRIVE revision panel propose as valuable but that are not considered important enough on the whole to include. 

The important reasons for discussing ARRIVE in this manuscript are to:

1. Contrast prior editorial suggestions for secrecy to current moves for more transparency and completeness.
2. Remind readers that 100% completeness is not possible; the most diligent efforts at completeness still requiring some editing of what is important versus what is not.
3. There is overlap but less than 100% of items of methodological importance versus items of welfare importance and
4. Proposal that the requisite editing of content by authors, reviewers and editors could be complemented by a commitment to allow readers to find the information that was edited out.

 

But, does that mean the information that is most important to allow critique and replication of the experiments, or to document animal welfare issues that may or may not affect data outcomes [43, 44]?

It is not clear why there should ever be a choice between reporting information pertaining to the evaluation of the science, and reporting information pertaining to the way experimental subjects were treated. This dichotomy seems arbitrary; both are crucial parts of a scientific publication.

Yes, a point I make in my 2016 analysis of descriptions of pain management in manuscripts. I do believe there will be times when a diligent use of the checklist will still leave out some welfare details a protectionist might yet want (maybe, how animals and staff were trained for a task). I am sticking to this position, which I have now re-worded as :   “Moreover, items selected for their ability to allow scrutiny of results and replication of methods may not answer protectionists or welfare researchers’ questions about a project [6b, 43]. I propose that greater openness would require publishing an author’s ARRIVE checklist as a supplement to the main paper, plus a user-friendly way for readers to request the welfare-relevant information that is important to them to know.”

 

The sentence also needs re-reading as it doesn’t quite make sense.

Authors and editors alone control what information to include or to edit out, and there are no easy invitational ways to ask for what the reader thinks is important.

I have never received an author’s ARRIVE checklist.

Doesn’t seem relevant to include. Not all journals use the checklists. Removed both of these sentences in my rewrite.

posting these checklists alongside the on-line manuscript as supplementary materials would allow concerned readers 

The sentence ends prematurely. Quite correct. That sentence fragment went away when I rewrote the paragraphs about ARRIVE.

 

Note that publishing ARRIVE checklists alongside manuscript would certainly help peer-reviewers and readers to identify relevant information more quickly, but the checklist only indicates where in the manuscript this information can be found; it does not negate the need to include the information in the paper.  While that’s correct, I’ve reviewed manuscripts for journals like JAALAS that claim to endorse ARRIVE, but found important info was missing, and reminded the authors and editors that had they actually used the ARRIVE checklist, they would have included the info. Had someone less attuned to ARRIVE done the review and the information was not in the published manuscript, publishing the checklist would allow readers to see this easily [and knowing they’d be publishing the checklist, they might have paid better attention to it]

5. Toward invitational openness, in the US context: Some proposals

Bad things happen to animals in laboratories. Sometimes, this is large or small non-compliance with regulations or approved protocols, the subject of exposés, self-reports to regulators, or government inspections.

Surely it's worth including here the suffering caused as part of licensed/approved projects (which can be severe) aside from any non-compliance issues where limits on suffering are exceeded – isn't the former the greater part?   I agree 100%. I’ve rearranged that section to put the discussion of welfare costs as the first paragraphs, and tried to make it more explicit that this is most of where the concern lies (as opposed to noncompliance). I have re-worked that whole section extensively

In the UK, the Home Office aggregates a year’s worth of institutional self-reports individual reports remain out of view [51, 54, 55].

The sentence structure needs improving.  I have removed that sentence

Also, it would seem appropriate to mention here that in the UK non-technical summaries of project licences (approved animal projects) are published retrospectively by the Home Office, in a set format including information on the predicated harms and how the 3Rs will be applied. This is a mandatory requirement of the ASPA. https://www.gov.uk/guidance/research-and-testing-using-animals#non-technical-summaries This occurs in other countries in Europe too. I have included info on the UK system, and it appears the EU wants member countries to collect and post these non-technical summaries.

have dealt with various laboratory non compliances over 40 years, stemming from neglect or ignorance over-exuberance

Insert "or” before “over-exuberance”  That sentence has been removed

This has been far overshadowed by approved activities, whether welfare compromises in the way animals are housed or the pain, injury and illness that modelling diseases entails.

The intention with this sentence is not clear - does it mean to convey that the scale of animal suffering is larger for approved activities?  That was the intent, though that sentence is now gone. I now say that “bad things” are “mostly … because some experiments will cause pain or distress or confinement or death.”

In the UK, the Concordat, giving credit to input from the RSPCA, has recognized a need to communicate the harms to laboratory animals and in its annual self-review, has identified a need for more of its signatories to do more on this front [4, 36, 56]

Many organisations on the Concordat steering group stressed the need for it to include a requirement to share information on the harms caused to animals, not just the RSPCA. I suggest “RSPCA” is deleted. I have reworded so that Concordat’s invitation to RSPCA is still in my article, but without upstaging other participants in the process:  “In the UK, the Concordat, which has invited and included RSPCA participation, has recognized a need to communicate the harms…”

Implanted metal rods

Seems odd wording and unscientific. Would “implanted head fixation devices and recording chambers” be better?  Yes, trying to find language that isn’t odd and unscientific, nor so scientific that it obscures meaning to non-scientists. I have changed “that their implanted metal rods are bothering them” to “that metal devices attached to their heads are bothering them.”

This proposal moves openness from the expanded posted information that characterizes Concordat membership to a right for open access to information and an obligation to work with the institutions' veterinarians and scientists to co-produce best practices.

It is worth recognising here or somewhere within the manuscript that proponents of openness and animal welfare advocates exist within the research community too and have been effective in influencing their peers. To acknowledge this would likely mean the article is received more positively by researchers.  Yes, earlier in the manuscript I now discuss what terms to apply to various actors in this field, including a note that “animal welfare advocates” are both outsiders and insiders (welfare scientists, ethics committee members, vets).

Animal welfare standards should combine the best available knowledge with sound values and ethics, and I propose that any professional groups that put forth welfare recommendations would do well to invite representation of welfare advocates for the most robust review of the ethics and

The sentence ends prematurely. You are correct.  The last sentence in that paragraph trailed off so I have replaced Animal welfare standards should combine the best available knowledge with sound values and ethics, and I propose that any professional groups that put forth welfare recommendations would do well to invite representation of welfare advocates for the most robust review of the ethics and …  with “Animal welfare standards should combine the best available facts with sound values and ethics, and I propose that any veterinary or scientific groups that put forth welfare recommendations would do well to invite representation of knowledgeable welfare advocates and protectionists.”

 

References

The formatting of the references needs checking to ensure they fit the journal style. Yes, always the most fun part of writing and revising a manuscript!

National Centre for the Replacement, R.a.R.o.A.i.R.N.R. The NC3Rs: Pioneering better science. 2020 [cited 2020 December 22]; Available from: https://www.nc3rs.org.uk.

The full name of the NC3Rs should be used here.

Reviewer 4 Report

Clearly written essay on a topic that requires constant attention and reminding of. 

One point about the text, page 7, under 4 'Animal protectionists, the status quo secrecy, and the New Openness', paragraph starting with 'One proposal": 

check sentence: 'posting these checklists alongside the on-line manuscript as supplementary materials would allow concerned readers.' Something seems to be missing?

There are a few typographical errors that require correction before publication. 

Author Response

Reviewer #4:

 

Clearly written essay on a topic that requires constant attention and reminding of.   Thank you very much

One point about the text, page 7, under 4 'Animal protectionists, the status quo secrecy, and the New Openness', paragraph starting with 'One proposal": check sentence: 'posting these checklists alongside the on-line manuscript as supplementary materials would allow concerned readers.' Something seems to be missing?  Quite correct. That sentence fragment went away when I rewrote the paragraphs about ARRIVE.

There are a few typographical errors that require correction before publication. 

Round 2

Reviewer 3 Report

The revised manuscript is improved and acceptable for publication. 

I'd like to make two further points on the ARRIVE guidelines:

The comment in the manuscript about item 8a is a bit misleading. First, this item recognises that weight might not be relevant for all studies/species. Second, criticising the item for missing "some unlisted factors such as litter size, number of females rearing the litter, which strain’s mitochondrial DNA a hybrid animal carries, or the microbiome profiles of the animals" is also a bit misleading because some of this information would be requested as part of item 8b (Provide further relevant information on the provenance of animals, health/immune status, genetic modification status, genotype, and any previous procedures).

The response to reviewers' comments states that the ARRIVE 2.0 paper does not provide a list of the 31 items suggested by the Delphi panel. This is incorrect; all this information is described in the supplementary information https://doi.org/10.1371/journal.pbio.3000410.s003  Microbiome was not suggested.

It is not that these suggestions were not important, but they were not appropriate to include in guidelines setting standards for all animal research. ARRIVE is the minimum common ground; there is obviously more information to include in any scientific paper and the relevance of various pieces of information will depend on the particular study but all the ARRIVE items should be relevant for all (or most) studies.