Editorial commitment to trust and integrity in science: implications for pain and anaesthesiology research*

We are a group of journal editors (online Supporting Information Appendix S1) dedicated to advancing discoveries and innovations in basic, translational and clinical research across anaesthesiology and pain-related disciplines, which play a crucial role in reducing the burden of pain, improving health, enhancing peri-operative outcomes and optimising healthcare delivery. Across scientific disciplines, concerns have been raised about research quality and trustworthiness 1, 2. While these challenges are not unique to pain and anaesthesiology research, we recognise this as a judicious opportunity to raise awareness and collaborate across our journals to align and strengthen initiatives to enhance research integrity, trust, and impact across our field. In a 2005 landmark paper, John Ioannidis concluded with the dramatic and troubling assertion that “most published research findings are false”, stimulating a large focus in the biomedical research community on understanding issues of integrity, reproducibility and replication that continues to be relevant to this day 3. Indeed, there are many instances in which authors, institutions, funders, publishers and journals have failed to embody the core values that produce trustworthy science. The trustworthiness of research is affected by both intentional actions (e. g. fabrication and falsification of data, lack of rigour and image manipulation) and unintentional actions (e. g. inadequate oversight, awareness and understanding of both technical and scientific issues). Most concerning are instances of research misconduct including fabrication, falsification or plagiarism, sometimes revealed by failure to replicate or reproduce results, duplication of publications, a rise in the number of retractions 4, 5 and calls for larger numbers of papers to be retracted (for example 2). In support of Ioannidis' disquiet, some reviews (for example 6, 7) report low replication rates of positive findings in the social and life sciences across clinical trials, epidemiological research and molecular studies. In anaesthesiology specifically, low agreement has been found between randomised clinical trials (RCTs) and meta-analytic findings for clinical pain interventions, where positive findings in meta-analyses were often not confirmed by subsequent large RCTs. For example, using individual patient data from RCTs published in Anaesthesia, Carlisle demonstrated that almost half of the databases had false data as detected from the duplication of figures, tables, and other data from published work; the duplication of data in the rows and columns of spreadsheets; impossible values; and incorrect data analytic strategies and calculations 8. Reproducibility, clinical validity and utility in pain and anaesthesiology research are often compromised by non-representative samples (e. g. limited representation on characteristics such as race, ethnicity, age, sex/gender or socio-economic status that do not match population-level data of those most affected by pain) 9-11; reliance on surrogate outcomes with limited clinical relevance; underutilisation of common data elements and core outcome sets; underpowered studies prone to false-negative results; and flawed statistical analysis plans that generate misleading conclusions 12. To ensure integrity of the literature, retraction of articles may be necessary due to such issues as major errors; data fabrication; plagiarism; or unethical research practices. The authors are encouraged to identify errors in their own work and may request a corrigendum to correct the literature. However, when ethical issues are brought to a journal's attention, they have a duty to investigate and, when there is conclusive evidence, to impose a retraction to alert readers that the findings and conclusions cannot be relied upon 13. Retractions, when reported, can have a widespread impact due to the interconnectedness of studies attributed to the same authors 14. In the field of anaesthesiology, the Retraction Watch Leaderboard indicates four of the top 10 authors are anaesthetists, and two of these individuals occupy the top two positions 15. Systematic reviews have summarised characteristics of retracted publications for research misconduct in pain (for example 16) and anaesthesiology research (for example 17). Concerns regarding retractions in all scientific fields are particularly noteworthy because they undermine trust in science, can have a lasting impact on conclusions made about treatments and, ultimately, impact clinical practice. In one study by O'Connell et al. , a set of eight untrustworthy trials (i. e. identified due to concerns including data anomalies and implausible results) in spinal pain was determined to substantially impact the results of subsequent recommendations made in systematic reviews and international clinical practice guidelines in management of spinal pain 18. Meta-research studies regarding open science practices highlight critical remaining gaps across many fields in reproducible research practices, open access data, and availability of protocols (for example 1). In 2018, Lee et al. examined open science efforts in the pain field including preregistration of trials; sharing code; data; reproducible workflows; and the use of reporting guidelines 19. Among 10 pain journals, a low level of engagement with open and transparent research policies was identified at that time. Cashin et al. also reviewed the policies of 10 leading pain journals and determined that there were few journal policies adhering to transparency standards for review and publication 20. These observations have fuelled many recent efforts and initiatives in open science including in pain and anaesthesiology research. Open and transparent research practices, as embodied in the ‘open science’ movement, provide a more complete and accurate report of the research conducted and what was found, and share important aspects of the research process (e. g. availability of study materials, data and code) 21. Trust and transparency are interwoven because when research is conducted and reported openly and transparently it increases confidence in the findings by enabling verification, replication and critical appraisal. Recommendations were made for short-term as well as more extended-term actions and behaviours for several different stakeholder groups (e. g. researchers, institutions, publishers, funders, policymakers and regulators and peer reviewers) to support trustworthy research within each of the core values of ENTRUST. These recommendations are intended to guide the development of a strategy for enhancing trustworthy research, rather than serving as a mandated policy. From the perspective of engagement with our journals, here we focus on recommendations for researchers and editors/publishers. We strongly recommend that researchers thoroughly review the proposed framework, which we as editors endorse, and explore the full suite of resources available through the ENTRUST-PE network project. These can be accessed at https: //entrust-pe. org and on the Open Science Framework (https: //osf. io/cua7g/? viewₒnly=ec1d9e6b1d774dbca9306ff5ae4dec67). The initiative is designed to support researchers to understand how to conduct and report science in a manner that enhances the transparency and trustworthiness of their work. By following these recommendations, researchers can provide the highest quality of research and facilitate confidence in pain science. Moreover, peer reviewers and consumers of research can be alerted to potential issues of methodological rigour, transparency, lack of equity and inclusivity, and markers of potential data inauthenticity or research misconduct that play a critical role in raising concerns to editors and publishers when these are identified. Recently, both the International Association for the Study of Pain (IASP) 23 and the European Pain Federation (EFIC) 24 endorsed the ENTRUST-PE initiative, recognising that trustworthy research not only benefits investigators and healthcare professionals but also serves patients and the public by promoting science that produces more effective pain management strategies. For a concise, actionable summary, we reproduce the guidance provided by O'Connell et al. , which outlines practical suggestions researchers can implement immediately to align with the core values of the ENTRUST-PE framework (Table 1) 22. Engage diverse potential patient and public partners before the project begins and involve them throughout the process. Plan PPIE at the very start (conception and planning) of the research process. Clearly report PPIE. Ensure the aims and questions of research are clearly conceptualised and communicated. Choose appropriate research designs for the research question. Provide adequate detail to reproduce study methodology. Pre-register your research, regardless of design. Update registrations with modifications to plans and results. Report all planned results regardless of the findings. Consider the range of possible alternative interpretations as well as study limitations in your interpretation of study findings. Evaluate journal policies on transparency and openness to inform potential improvements As highlighted in several prior reviews 19, 20, journals can use existing tools to conduct self-assessments of their policies and procedures. Tools have been developed to facilitate transparency, including the Transparency and Openness Evaluation Tool 20 and the Centre for Open Science (COS) Transparency Factor 25. As a first step, pain and anaesthesiology journals can sign on to COS as signatories (if they are not already) to express support for transparency and openness principles. In addition, the Transparency and Openness Factor metric provides information on where opportunities exist for improvement, which can contribute to decision-making and policy development by editors and publishers to improve transparency and openness. For example, this can guide changes to journals 26 along such areas as research pre-registration where appropriate; reporting guidelines; open data analytic codes and materials; transparent reporting of authorship contributions; and defining the role of the corresponding author as the point of contact for accountability and transparency. Gain access to automated tools to improve transparency and trustworthiness, while fostering innovation in new methodologies Innovations are needed to support a range of automated processes to enhance transparency and integrity. At present, multiple checks of transparency and trustworthiness are conducted manually by reviewers and editorial teams. Journals can carry out protocols in the workflow prior to the initiation of peer review around many indicators for quality, trustworthiness and ethics concerns such as possible image manipulation; internal inconsistencies in referral to figures and tables; text plagiarism; adherence to reporting checklists; registration of systematic reviews; identifying discrepancies between research registrations (e. g. ClinicalTrials. gov) and reporting of clinical trial outcomes; and the inclusion of relevant animal and human review board approvals, to name a few. One example of checking for random sampling in RCTs is the method suggested by Carlisle et al. , but this is labour-intensive and does not apply where recruitment has not been entirely random 27, 28. Although there are automated processes to check for duplicate text, there are none yet to assist with these data integrity checks, and this requires dedicated staff effort. In this regard, several publishers/journals have introduced advanced technology (i. e. artificial intelligence) to detect duplicate manuscript submissions across all their respective journal platforms. Others have initiated ‘flag alerts’ for authorships that include individuals who have been associated with multiple manuscript retractions. Additional automated processes are needed to help authors, reviewers and editors to standardise more thorough yet efficient approaches to enhance transparency of reporting and enhance trustworthiness of published work. Create a platform for collaboration among editors of leading pain and anaesthesiology journals Offer educational opportunities and resources to professional societies, forums, journal reviewers and early-career professionals Journals can be an important resource to guide and teach researchers and consumers about transparency and integrity standards, and we see several opportunities to make an impact. For example, one opportunity to introduce standards for trustworthiness is through the system adopted by several of our journals for manuscript review mentorship and editorial fellowship that provides tutorials, training and experience reviewing or managing manuscripts. Moreover, we can leverage our partnerships with the professional societies that are associated with many of our journals to offer training and instruction on transparency and integrity. This could include professional development programmes for reviewers, as well as early-career faculty (e. g. North American Pain School) and offerings developed by groups such as the International Association for the Study of Pain's Early Career Network (https: //www. iasp-pain. org/early-career-network) and by setting expectations for presenting and sharing research at scientific meetings (e. g. checking for retractions of any published studies discussed in presentations). Our journals can help disseminate information on tools targeting researchers directly 30 that can be made available to authors in a toolkit to assist them in pursuing values of openness and integrity. For example, statistical assessment tools to assess the accuracy of reported findings may be implemented by running simple, automated error checks, such as using the StatCheck tool 31. It should be stressed that increasing the education provided enhances quality, reliability, and integrity. Ultimately, as a community of scientists and clinicians in pain and anaesthesiology, we must recognise that trust is a dynamic and multifaceted concept. It requires ongoing effort to maintain; once lost, it is hard to regain, and it is built through consistent actions and open communication. Resources are available through the ENTRUST-PE framework that can guide actions and values to promote trust and integrity. These principles apply to all scientific fields beyond those that are pain-related, and we encourage other specialties to harmonise such efforts. As editors, we will work together to advance the trustworthiness of research through upholding rigorous standards, ethical conduct, and open dialogue. By doing so, we can strengthen the foundation of trust in research and ensure that anaesthesia and pain science continue to optimally inform care for people undergoing anaesthesia or living with pain. TMP receives research grant funding from NIH, provides consultation to TriveniBio, and serves as Editor-in-Chief, The Journal of Pain. DB serves as Editor-in-Chief, European Journal of Pain. KDD serves as Editor-in-Chief, PAIN. HCH receives research grant funding from NIH and serves as Editor-in-Chief, British Journal of Anaesthesia. RWH has received co-operative research grants from NIH and Nevro, Inc. , provides expert/consulting to State Farm, and serves as Editor-in-Chief, Pain Medicine. JK is the Research Director of ManagingLife and serves as Editor-in-Chief, Canadian Journal of Pain. JJP is Editor-in-Chief, Anesthesia & Analgesia. TJP is a co-founder of and holds equity in 4E Therapeutics, NuvoNuro, PARMedics, Nerveli, and Doloromics, has received research grants from AbbVie, Eli Lilly, Grunenthal, Evommune, GSK, Hoba Therapeutics, and the National Institutes of Health, and serves as Editor-in-Chief, Neurobiology of Pain. MVdV has received honoraria for lectures and/or consultancy from CSL Behring, CSL Vifor, BBraun, Werfen, Viatris, CAF-DCF and Aquettant, and serves as Editor-in-Chief, European Journal of Anesthesiology. MES is Senior Medical Advisor, APURANO Pharma, and serves as Editor-in-Chief, Journal of Pain Research. SKWS holds the Dr Jean Templeton Hugill Chair in Anesthesia, supported by the Dr Jean Templeton Hugill Endowment for Anesthesia Memorial Fund (Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada) and gratefully acknowledges the Department of Anesthesia, St. Paul's Hospital/Providence Health Care (Vancouver, BC, Canada) for ongoing support. SKWS serves as Editor-in-Chief, Canadian Journal of Anesthesia. DCT holds the John and Emma Bonica Endowed Chair in Anesthesiology and Pain Research at the University of Washington, has received research grants from NIH and NIOSH, and has provided consultation to Vertex. DCT is also Associate Director of Analgesic, Anesthetic, and Addiction Clinical Trials Translations, Innovations, Opportunities, and Networks and Pediatric Anesthesia Safety Initiative (ACTTION/PASI). DCT serves as Editor-in-Chief, Clinical Journal of Pain. MDW serves as Editor-in-Chief, Anaesthesia. TLY is co-founder of Raft Pharmaceuticals, serves on the Scientific Advisory Board for Navega Therapeutics, and serves as the Editor-in-Chief for Frontiers in Pain Research. DY is a partner in a current Horizons grant, holds equity in BrainsGate and Theranica, and receives honorariums from Dr Reddy and from IASP. DY serves as Editor-in-Chief, PAIN Reports. No new data were generated or analysed in this study. Data sharing is not applicable to this article. No competing interests related directly to this work. Appendix S1. Details of editorial affiliations Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.