What does it mean for scientific evidence to be trustworthy? When we think of trust, we might reflexively think about methodological rigor and features of the design and conduct of the study that increase or reduce the risk of bias in a study. But they are only part of the story.

A few years ago we identified substantial concerns around the trustworthiness of some published clinical trials in the field of pain management. Those concerns focused not on risk of bias but on multiple aspects of research governance and integrity and the authenticity of the data in those studies. We went on to find that these trials had had a powerful and worrying impact on the evidence base for the treatments they studied. This got us thinking about trustworthiness more broadly.

In 2023 we received funding from the ERA-NET NEURON Co-fund to bring together a network of experts to create a framework for enhancing the trustworthiness of evidence in pain. The ENTRUST-PE project brought together an international team from the world of pain research.

We included pre-clinical and clinical researchers across the range of career stages, senior journal editors, experts in a range of methodologies, scientific and clinical disciplines, and importantly people with lived experience of pain. We met regularly across a year and through discussion, debate and consensus we created the ENTRUST-PE framework.

Our discussions identified multiple threats to the trustworthiness of data. Beyond methodological rigor, these included incomplete research governance, a lack of diversity and inclusivity, inadequate patient engagement, incomplete reporting, a lack of data accessibility and transparency, and a failure to communicate findings with appropriate balance. These issues span pre-clinical research, clinical trials and systematic reviews and impact the development of clinical guidance and practice. Research misconduct and inauthenticity present a further critical risk.

Each of these core values should drive universal actions and behaviors in researchers and stakeholders across all roles and stages of the research process. This means taking practical steps to meet standards of best practice, to make our research and our research communities genuinely equitable, diverse and inclusive, to proactively engage and involve people with lived experience of pain in the research process, to ensure rigor and transparency in our methods, to embrace open research practices, to avoid spin and report our results with balance and to be vigilant to and act fast to recognize inauthentic data and potential misconduct and remove it from the literature.

Whose responsibility?

It would be easy to think this is all about researchers and their choices. But researchers operate within a complex ecosystem of stakeholders and power-brokers that contains myriad pressures and incentives that can positively or negatively affect behaviors.

This includes institutions that conduct research, research funders, journal editors, publishers and peer reviewers, regulators and policymakers, consumers of research and researchers themselves. All have a vital role to play. ENTRUST-PE offers recommendations for each stakeholder group for each of the core values. Many or most researchers routinely perform multiple roles in the ecosystem, holding different levels of power in each. We ARE the system. With this lies an opportunity and an imperative to promote and model the values and behaviors of trustworthy evidence consistently through our actions across each of these roles (figure).

Toward change

In a recent "Call to Action" article published in the Journal of Pain, we suggested that change is needed from all the players in the ecosystem to incentivize and normalize better processes and behaviors and that it will require resources, education and, for all of us, reflection and humility about our own practices. There is a collective responsibility to foster positive change and prioritize the development of our research culture(s) to truly embrace research integrity. On that basis, we are delighted that, at the time of writing, the International Association for the Study of Pain (IASP), the European Pain Federation (EFIC), the Australian Pain Society, and the Editors-in-Chief of 15 International Pain and Anesthesiology journals have all chosen to officially endorse the ENTRUST-PE framework.

But for the individual researcher, we know that this can feel overwhelming, so we suggest they might conduct an inventory of the current core values they are already incorporating and then commit to seeing what changes they can implement immediately and what medium-to-long-term changes they can plan a path towards. A "commitment to making one change now" may be more realistic than “do everything immediately." We have attempted to offer clear and specific short-term actions for each element of the framework, including suggestions for "What change can I make now?" (box).

Resources

As part of the project, we have published a detailed White Paper that outlines the challenges and recommendations in more detail. We created factsheets with a summary of the recommendations for a wide range of those stakeholder groups and an explainer for patients and the public. All of these are free to download and share. We also curated a collection of excellent external resources that we signpost researchers to support them towards each Core Value. All are openly available on our project website.

White Paper

Website

Article

Is it really about pain?

We undertook this project with and for the pain research community. But it quickly became clear that few, if any, of the challenges and solutions are specific to pain research. We think and hope the framework could have a life and a use in health research more broadly.

Too often, critical conversations on methods and processes in research fail to adequately penetrate beyond the methods community. The benefit of our focus on pain is that it raises this critical issue and starts a conversation about better methods and practices within our community, where it has a better chance of being heard.

How important is this?

None of this is easy. But it is worth considering for a moment the unlimited costs and consequences of not acting: research waste, stalled progress, inadequate care, and potentially avoidable suffering. We hope that ENTRUST-PE amplifies the conversation about trust and integrity in research and offers support and tools for the research community to enhance the trustworthiness of our evidence.

References

1. O’Connell NE, Moore RA, Stewart G et al. Investigating the veracity of a sample of divergent published trial data in spinal pain. Pain 2023;164:72–83. https://doi.org/10.1097/j.pain.0000000000002659

2. O’Connell NE, Moore RA, Stewart G. Trials we cannot trust: Investigating their impact on systematic reviews and clinical guidelines in spinal pain. J Pain 2023; 24:2103-2130. https://doi.org/10.1016/j.jpain.2023.07.003

3. Branney PE, Brooks J, Kilby L et al. Three steps to open science for qualitative research in psychology. Soc Personal Psychol Compass 2023;17:e12728. https://doi.org/10.1111/spc3.12728

4. The British Psychological Society Research Board. Position Statement: Open Data 2020. https://www.bps.org.uk/guideline/open-data-position-statement

5. O’Connell N, Belton J, Crombez G et al. Enhancing TRUST in pain evidence: The ENTRUST-PE framework. A Summary for Researchers. 2024. https://doi.org/10.31219/osf.io/y6e3s_v1

6. O’Connell NE, Belton J, Crombez G et al. Enhancing the trustworthiness of pain research: A call to action. J Pain 2024:104736. https://doi.org/10.1016/j.jpain.2024.104736