Guest bloggers: Carel IJsselmuiden (COHRED, University of KwaZulu-Natal, South Africa); Bipasha Bhattacharya (COHRED, Corresponding Author, rfi@cohred.org), Julia Vallauri and Eric Martin (Institut de recherche pour le développement, France).

In celebration of World Health Day on April 7, 2022, the team behind the Research Fairness Initiative have written a guest blog on their effort to increase fairness in research collaborations across the globe. Although this initiative was inspired by research in global public health, the framework can be applied to any and all research collaborations in order to allow contributors to consider fairness and equity in place in their collaborative projects.

Good health is crucially dependent on research. On good research, on research that is excellent, relevant, ethical and also timely, perhaps. Such research is rarely done by individuals, in isolation, as a garage-based effort – although it could be. In reality, excellent research requires more than individuals – it requires top institutions, supportive environments, financing, supportive legislation and international treaties, rewards and awards, translation opportunities to scalable innovations, and much more. To capture this complexity, we will use the term ‘research systems’ or ‘research and innovation systems’.

Low- and middle-income countries (LMICs) often lack many of these components that are essential to a high-performing research and innovation system. That is no surprise, given that many other sectors in LMICs also lack many of the components that make these sectors work better in high-income environments. In fact, so strong is the generalized perception of under-performing research and innovation systems in LMICs, that even the many current calls for and initiatives to achieve better ‘pandemic preparedness’ rarely mention the need for capable R&D systems in LMICs. And this is in spite of overwhelming evidence that those LMICs with high performing R&D capabilities are not only less affected by ‘vaccine inequity’ but also delivered the largest contributions towards vaccinating the populations of other LMICs.

Capable research, development and innovation systems are a basic requirement for LMICs. They should invest themselves, and the ‘global community’ should support this. This may sound simple, but when looking at the dance floor of international research collaborations, the movements do not recognizably add up to a tango. The mostly divergent, project-based efforts driven by prescriptive (high-income country) funders rather than by national (LMIC) priorities, without clear links to financing the scaling of results, and without systematic efforts to improve tango skills, dancing shoes or the ball-room itself, are more conducive to sore toes, falls, profanities and disappointment than to achieving gradual increases in performance, outputs and outcomes.

‘Development agencies’ and philanthropies supporting LMICs rarely recognize the importance of developing research capabilities in LMICs as a essential to success, especially sustainable success. This applies particularly in global health research as the COVID-19 pandemic demonstrates so clearly.

Given this conundrum – i.e. the need for long-term support for the complex research systems in LMICs combined with the absence of any serious, targeted and long-term funding for this and the often low or absent own investments by LMICs themselves – we believe that the evidence is growing that a continuing effort to improve the fairness and equitability of research partnerships is both essential and catalytic. To go back to the dance floor – would the tango not be immensely more productive and enjoyable if all partners have access to similar skills, training, music or shoes – even if on loan for a while?

The Research Fairness Initiative (RFI) (https://rfi.cohred.org)

The RFI is a direct response to the need for a pragmatic instrument to improve how research and innovation partnerships with low- and middle-income countries (LMICs) can be improved continuously. The RFI is unique. It can generate the transparency and systematic institutional learning required to improve how organisations engage in and manage research and innovation collaborations in a fair and equitable manner for greater impact. While its priority focus was on collaborations between institutions in high and those in low- and middle-income countries, it is clear that the RFI is also appropriate to collaborations between high-income countries.

The RFI elevates research partnerships from ad hoc arrangements between individual researchers to key performance areas for all main actors in research and innovation, in particular:

• Research and Academic institutions
• Government Departments responsible for research and innovation
• National Research and Innovation Agencies
• Research Funders
• Private Sector organizations with a major research and innovation portfolio
• International organizations, large non-profits, and others.

Equitable and fair research collaborations are crucially important to enable LMICs to develop the excellence and sustainability of their research institutions and systems. At this time, the RFI provides the only pragmatic, systematic and global approach to improve the way research collaborations are done – even between high-income institutions themselves.

The RFI has been co-designed through wide and extensive global consultations. Its process can be viewed here : https://rfi.cohred.org/rfi-history/. Its continued improvement is done with all organisations using or supporting the RFI.

The RFI ‘System’ consists of two complementary components:

1. RFI Reporting – biennial institutional self-assessments. The RFI framework of questions and indicators provides a pragmatic tool for institutional self-assessment of the policies and practices used to promote fairness and equitability in their research collaborations. Its focus is forward: ‘How to improve policies and practices in the next 2 years’. Responding to the questions in the RFI Framework often provides a first opportunity for organisations to strategically and systematically assess their own partnership policies, practices and expectations. A short overview of questions and indicators can be found at: https://rfi.cohred.org/wp-content/uploads/RFI_Summary_Guide_1.pdf

2. The RFI Global Learning Platform aggregates and analyses the information provided by institutions in their RFI Reports. Once fully developed, it will provide both real-time and special reports to enhance the evidence base the world of research needs to improve research partnerships and, where possible, reach global agreements on standards or benchmarks.

The full RFI website information can be viewed here: https://rfi.cohred.org

For full certification, organisations have to publish their RFI reports on their own, corporate websites AND enable a comment function for readers.

Once complete, the RFI website will republish these reports and encourage further comments that will remain anonymous to the organisation. In this way, the RFI System should become a global platform for learning and action.

RFI Reporting Organisations

The RFI has had a slow but gradually increasing uptake since its release as ‘version 1’ in 2019. We now have reports from almost all the main research actors listed above and more. The COVID-19 pandemic did not help its progress, but the pace of completing reports is picking up. There are currently five completed reports available (Nova University of Lisbon (Portugal), World Health Organization (WHO/TDR), Univ Alioune Diop de Bambey (UADB, Senegal), IRD (Institut de Recherche pour le Développement, France), and the Swiss TPH (Switzerland)). There are four more submitted or close to completion (Fondation Botnar (Basel, Switzerland), University of Cape Town (South Africa), Epicentre Paris (MSF, France), CAPRISA (Centre for the AIDS Programme of Research in South Africa (South Africa)), and we are aware of several organisations in the process of obtaining approval to start their RFI reporting.

Although the number of institutions is small – looking at this list of ‘early adopters’, the results of these reports is likely to impact on many global, regional and national partnerships.

There have also been other uses of the RFI System, for example, The Philippines made 2021 the year of Research Fairness using the RFI, while the Ministers of Health of the Community of Portuguese Language Countries (CPLP) have recommended the RFI as guide for intra-CPLP health research collaborations.

The Evidence-base is growing

The sample is still small, but early lessons include:

• Completing the RFI Report is for many organisations the first and only time for strategical assessment of their own partnership policies, practices and expectations. It has proven to be an eye-opener for all, without exception.
• It is a challenge to change perspective – away from writing a ‘report card’ focusing on past performance towards preparing a two-year, forward looking improvement plan for fairness and equitability in research collaborations. Once the perspective has changed, it encourages interest, engagement, creativity and intent to learn how others are doing.
• There are original policies and practices not known outside organisations that are clearly going to be helpful to others – and can possibly generate global consensus for standards or benchmarks in future.
• Different organisations voiced different concerns. These may include a fear of funder backlash should responses to financial management in the RFI be answered inadequately. (We have informal evidence to the contrary – awareness of needs for support generate support). Additional administrative load which, additionally, needs to be paid for from scarce core funding. (With the new interactive web-based RFI reporting platform, the production of the first draft report takes less than a day – once the information to questions is available. At the same time, all questions are actually relevant for any self-respecting research actor. If it takes a lot of time to find the answers – that is not because the RFI is complex, but because you should have measured these indicators in the first place). Or the concerns may be getting comments from partners. (Actually, transparency is what enables discussion and negotiation – the basis for great and lasting partnerships).

Next steps for the RFI

It seems the RFI is in the early phase of adoption, and we anticipate a faster uptake from all constituencies and also from ‘enablers’, like journals and funders. We look forward to journals and funders making it a requirement for any lead organisation of research collaborations involving LMICs to submit their RFI reports. Imagine if everyone would play ball…

The RFI and World Health Day

Underlying global health is high quality research. Underlying high quality research are great researchers and research systems. Global health, resilience, pandemic preparedness and a future able to deal with environmental challenges will be well served by focusing far more clearly on the sustainable development of research and innovation capabilities in and with LMICs. Equitable and fair partnerships are essential in achieving this.

Key references:

Carvalho A, IJsselmuiden C, Kaiser K, et al. (2018) Towards equity in global health partnerships: adoption of the Research Fairness Initiative (RFI) by Portuguese-speaking countries. BMJ Global Health 3:e000978. http://dx.doi.org/10.1136/bmjgh-2018-000978

Lavery JV and IJsselmuiden C. (2018) The Research Fairness Initiative: Filling a critical gap in global research ethics [version 1; peer review: 2 approved]. Gates Open Res 2:58. https://doi.org/10.12688/gatesopenres.12884.1

IJsselmuiden C, Garner C, Ntoumi F, Montoya J, Keusch GT (2021) R&D – more than sharing vaccines. A complete change is needed in the approach to and funding of global preparedness. Think Global Health. https://www.thinkglobalhealth.org/article/rd-more-sharing-vaccines

Further reading:

In September 2021, PLOS launched a policy on Inclusivity in Global Research, which aims to improve reporting of global research. Authors conducting research of this nature who submit research to PLOS journals for consideration for publication may be asked to complete a questionnaire that outlines ethical, cultural, and scientific considerations specific to inclusivity in global research.

Disclaimer: Views expressed by contributors are solely those of individual contributors, and not necessarily those of PLOS.

Cover image credit: Rich Briggs, USGS. Public Domain.

The post It takes two, or more, to tango. Why a focus on fair and equitable research collaborations is essential for global health – and how to achieve it. appeared first on EveryONE.

In this blog post Adrian Smith from Norecopa discusses the role that the PREPARE Guidelines and Website play in improving the robustness and translatability of animal studies.

Criticism of animal research has come from an unexpected quarter in recent years: scientists themselves have expressed concerns about the poor reproducibility and translatability of preclinical studies [1,2]. The criticism includes, among other things, concerns about underpowered experiments, bias caused by a lack of randomisation and blinding, and incorrect use of statistical analyses in attempts to demonstrate significance.

Working inside animal facilities has given me insight into some additional causes of this state of play. From that viewpoint, it quickly becomes clear that high-quality animal research is utterly dependent upon collaboration, from the earliest possible stage, between scientists and animal care staff. While scientists have the insight and expertise to plan relevant experiments, they rely on those with intimate knowledge of the animals to translate these plans into valid and robust in vivo studies. Even simple events such as a scientist’s request for a blood sample trigger questions about a range of issues, including factors that affect the quality and shelf-life of the sample, and the physiological effects of the blood loss on the animal [3]. Similar practical questions arise for every aspect of a study, many of which will never be reported in the publications ensuing from the work. These include assessment of the facility’s standard and competence, staffing levels, refinement and standardisation of procedures, distribution of costs, and health and safety concerns. Early dialogue with animal care staff, who are often proficient at lateral thinking, may reveal better ways of conducting a procedure, thanks to their previous experience. If these questions are inadequately addressed, we risk that animal-related issues become the greatest sources of variability or poor validity in a study. Mutual respect for the skills and knowledge of scientists and lab animal staff alike is therefore paramount if we are to improve reproducibility and translatability.

Although better reporting is often promoted in connection with the reproducibility crisis, this is only part of the solution. There is no doubt that improved reporting is needed, both to aid evaluation of the quality of experiments and to enable them to be repeated. Inadequacies that have been demonstrated include faulty study design, poor descriptions of the animals, and insufficient detail about their environment and peri-operative care [4-6]. Reporting guidelines have been published for many years to address these issues [7], but without better planning we are merely trying to improve the description of a burnt cake: we need to go back to the kitchen and change the recipe. Lack of compliance with reporting guidelines, or even knowledge of them, despite journal endorsement, is also a major problem [8-9].

In 2016, the EU Commission was faced with a European Citizen’s Initiative (ECI) to ban animal experimentation [10]. Public opinion plays an important role in defining animal research, and we have both legal and ethical obligations not to waste animal lives. Part of the Commission’s response to the ECI was to hold a meeting entitled Non-Animal Approaches – The Way Forward in Brussels in December 2016 [11]. Here, almost for the first time, I heard participants discussing the need for planning guidelines. Spurred on by this, we published the PREPARE guidelines in 2017 [12]. PREPARE consists of a checklist covering 15 main areas (Figure 1) and a website with supplementary information and references to resources for each of the 40 topics on the checklist (norecopa.no/PREPARE).

PREPARE guides scientists through all the steps of planning animal experiments. The principles embodied in PREPARE apply to all in vivo studies, both in dedicated facilities and in the field, regardless of species used and the level of their legal protection. The PREPARE checklist is divided into three sections: formulation of the study, dialogue between the scientists and animal care staff, and quality control of the components in the study. Some of these topics will be the responsibility of the animal facility rather than of the research team, but it is important that all have been considered. The first section gives advice on literature searching (including systematic reviews), legal aspects, harm-benefit assessment, humane endpoints and other ethical issues, experimental design and statistical analysis. The second section covers important practicalities such as the distribution of labour and responsibilities, facility evaluation and competence, as well as health and safety issues. The third section provides tips on quality control of all the stages of a preclinical study, including the test substances, procedures, the animals and their environment, husbandry methods, humane killing and necropsy routines. PREPARE aims to give practical advice which will ensure both scientific rigour and optimal animal welfare.

Although only recently published, the principles in PREPARE were developed over a 20-year period, during which earlier versions were discussed with scientists on courses in Laboratory Animal Science. PREPARE is also full of lessons learned by animal facilities when applying for international accreditation. The checklist has proved popular, it has been translated into over 20 languages, and the website is updated regularly as new resources are published. A 3-minute cartoon film, with optional subtitles in many languages, has been produced to illustrate the main principles embodied in PREPARE (norecopa.no/PREPARE/film).

We are now working to encourage uptake of PREPARE by scientists on a voluntary basis. This is being done by arranging workshops and webinars, through newsletters and social media, and by contacting research animal facilities. PREPARE is not intended to be yet another hurdle on the road to publication. On the contrary, it is our hope that PREPARE will be seen as a means of ensuring that all the issues likely to be raised by reviewers will have been addressed before it is too late. PREPARE should also prove helpful to those who evaluate proposals for animal studies, including funding bodies, ethical review boards and regulatory authorities.

To complete this cycle of increased quality, I would also like to see more emphasis in scientific papers on the efforts the authors have made to replace, reduce or refine animal use (“the three Rs”) [13]. This emphasis is unfortunately not a clear feature of reporting guidelines. We owe it to the general public, to our funders and to the animals. We must do this prominently, since many bibliographic databases index only the title and abstract of a paper. My 3-step recipe for better science is therefore:

1. Be PREPAREd: plan in collaboration with animal care staff from day 1
2. Demonstrate that you have ARRIVEd: submit a manuscript which documents how the potential causes of irreproducibility have been tackled
3. Flag the 3Rs: highlight efforts to refine, reduce or replace animal use

I am optimistic. In the words of Edward Everett Hale [14]:

Coming together is a beginning, Keeping together is progress, Working together is success.

About the Author

Adrian Smith studied Veterinary Medicine at Cambridge University, graduating in 1979. After working in clinical veterinary practice in the UK, he emigrated to Norway and held positions related to animal research at the Norwegian School of Veterinary Science for 30 years. He was awarded his PhD in 1988 for his work on seasonal variations in the reproductive activity of the Arctic fox (Vulpes lagopus). He held the Chair in Laboratory Animal Science from 1988 to 2011, and led the work of obtaining and renewing international accreditation of the School’s laboratory animal facilities. During this period he also arranged over 50 courses in Laboratory Animal Science for scientists and technicians, and served on the Norwegian Animal Research Authority, during which time he was involved in writing the draft of new national legislation on animal research.
   Adrian has been Secretary of the Norwegian platform for the replacement, reduction and refinement of animal experiments (Norecopa) since its foundation in 2007. He has led the work of developing Norecopa’s website (norecopa.no) into a source of international resources for scientists and the laboratory animal community. The website currently has over 9,000 pages and a quarter of a million hits annually. He led the work of publishing the PREPARE guidelines for planning animal experiments. Collaboration with international colleagues is an important part of this work, and the PREPARE checklist has been translated into over 20 languages. Other tasks for Norecopa have included the organisation of international consensus meetings on the care and use of animals in research, the production of position statements and guidelines about animal procedures, and the regular issue of newsletters in English.

References

1. Munafò MR, Nosek BA, Bishop DVM, Button KS, Chambers CD, Percie du Sert N, Simonsohn U, Wagenmakers E-J, Ware JJ, Ioannidis JPA (2017) A manifesto for reproducible science. Nat. Hum. Behav. 1, 0021.
2. Begley CG, Ioannidis JP (2015) Reproducibility in science: improving the standard for basic and preclinical research. Circ Res. 116(1):116-126. doi:10.1161/CIRCRESAHA.114.303819
3. Blood sampling. https://www.nc3rs.org.uk/3rs-resources/blood-sampling Accessed 30 September 2020
4. Baker, M (2016) 1,500 scientists lift the lid on reproducibility. Nature 533:452–454. doi:10.1038/533452a
5. Avey MT, Moher D, Sullivan KJ, Fergusson D, Griffin G, Grimshaw JM, Hutton B, Lalu MM, Macleod M, Marshall J, Mei SHJ, Rudnicki M, Stewart DJ, Turgeon AF, McIntyre L (2016) The Devil Is in the Details: Incomplete Reporting in Preclinical Animal Research. PLoSONE 11:e0166733. doi:doi:10.1371/journal.pone.0166733
6. Bradbury AG, Eddleston M, Clutton RE (2016): Pain management in pigs undergoing experimental surgery; a literature review (2012-4). Br. J. Anaesth. 116: 37-45. https://doi.org/10.1093/bja/aev301
7. Norecopa (2020) Reporting guidelines. https://norecopa.no/more-resources/reporting-guidelines Accessed 30 September 2020
8. Reichlin TS, Vogt L, Wurbel H (2016): The Researchers’ View of Scientific Rigor-Survey on the Conduct and Reporting of In Vivo Research. PLoS One 11: e0165999. 2016/12/03. DOI: 10.1371/journal.pone.0165999.
9. Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen O, Rawle F, Peynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Wurbel H (2020): The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 18(7): e3000410. doi: 10.1371/journal.pbio.3000410
10. Stop Vivisection. European Citizens’ Initiative. https://europa.eu/citizens-initiative/stop-vivisection_en Accessed 30 September 2020
11. Non-Animal Approaches – the Way Forward. Report on a European Commission Scientific Conference held on 6-7 December at The Egg, Brussels, Belgium. ISBN 978-92-79-65840-2. doi: 10.2779/373944 https://ec.europa.eu/environment/chemicals/lab_animals/3r/pdf/scientific_conference/non_animal_approaches_conference_report.pdf Accessed 30 September 2020
12. Smith AJ, Clutton RE, Lilley E, Hansen KEAa, Brattelid T (2018) PREPARE: Guidelines for planning animal research and testing. Lab. Anim. 52(2): 135-141. doi: 10.1177/0023677217724823 Accessed 30 September 2020
13. Norecopa (2020) The Three R’s. https://norecopa.no/alternatives/the-three-rs Accessed 30 September 2020
14. Edward Everett Hale. https://en.wikiquote.org/wiki/Edward_Everett_Hale Accessed 30 September 2020

Featured Image: Pixabay CC0

Views expressed by Guest Bloggers are solely those of individual authors, and not necessarily those of PLOS.

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