Cannibinoid and cannibis-based medicines for pain tend to have significant amounts of narrative bias in the title and abstracts. (Photo by Nataliya Vaitkevich)
A group of European, Australian, and U.S. researchers identified several factors that reduce the trustworthiness of pain research, according to a review published in The Journal of Pain in 2025. These factors include:
- Failure to meet current standards of governance and integrity
- Undeclared or poorly managed conflicts of interest
- Unethical practices (e.g. false reporting, fabricating data)
- Inadequate quality assurance and/or poor data stewardship
Led by Dr. Neil O’Connell of Brunel University in the U.K., the researchers gave an example where 86% of systematic reviews of cannabinoid’s efficacy for pain management were rated as having low or critically low confidence with all 36 of the included studies having “unclear” or “high risk of bias.”
They also identified 374 animal trials that have “very poor” quality in methodology reporting.
In fact, a 2024 study of cannabinoid and cannabis-based medicines for pain by Moore et al. found 24% (8 out of 34) of the randomized-controlled trials has “moderate or severe narrative bias in the title and abstract and 17% (11 out of 64) of systematic reviews.
“There was no significant or meaningful association between narrative bias and study characteristics in correlation or cluster analyses. Bias was always in favour of the experimental cannabinoid or cannabis-based medicine,” Moore et al. wrote.
Meanwhile, O’Connell et al. cited moderate to high levels of spin in 33% of abstracts in analgesic studies.
“The critical lack of rigour and transparency across cannabinoid research resulted in substantial, avoidable and ongoing clinical uncertainty and research waste,” O’Connell et al. wrote. “Research waste is reflected in terms of wasted funding, resource, researcher and participant time and in opportunity costs. This is not an issue limited to research on cannabinoids, but can be seen across other fields of pain evidence.”
They added that pain research that overlooks certain societal groups—such as race, women, older adults, rural residents, or veterans—or entire global regions, reduces the applicability of findings both nationally and internationally.
“This can reinforce inappropriate conclusions and inequities of care and fails to meet the fundamental ethical pillar of justice,” O’Connell et al. wrote. “Yet each of these issues of systemic underrepresentation remain common across pain research.”
A potential solution?
The researchers proposed the ENTRUST-PE framework (ENhancing TRUSTworthiness in Pain Evidence) to address the systemic problems in pain research. The framework revolves around seven core values:
- Equity, inclusion, and diversity: Research must include groups that are not typically included to improve generalizability in large populations.
- Governance and integrity: Research must comply with the best standards of governance and integrity.
- Patient and public involvement: Allow people to share their pain experiences and include them as part of research.
- Methodological rigor: Promote high-quality research methods, and avoid and call out questionable research practices.
- Transparency and openness: Make research as transparent and open as possible.
- Balanced communication: Report all results regardless of the findings; make clear distinctions between reasonable interpretation and speculation, exploratory vs. confirmatory research.
- Data authenticity: Be aware of markers of potential inauthentic data and research misconduct; commit timely action to remove or correct such errors.
A visual summary of the ENTRUST-PE Framework. (Image by the ENTRUST-PE project, licensed under CC BY 4.0)
To adopt these values into practice, O’Connell et al. recommended that researchers “normalise activities” that promote these core values throughout the research processes from project inception to publication. For editors and publishers, they should “safeguard” these core values through the peer-review process.
“To guard against bias, we must first acknowledge and recognise its effects,” O’Connell et al. wrote. “It is important to reflect, with honesty and humility, on your position as a researcher, your relevant professional, financial and personal background and interests, financial and practical constraints and how these factors may influence your approach to the research.”
They also call for “seeking engagement and partnership with appropriately diverse communities” and allow patients to share the research process with researchers when engaging in pain research. “[These] are key features of high-quality research that ultimately address the significant burden and inequities in pain and pain care,” they wrote.
While it seems like the responsibility of promoting these core values and trustworthiness fall on the shoulders of researchers, O’Connell et al. wrote that larger factors can influence how research is conducted, such as pressure, politics, and incentives.
“Regulators and Policymakers are gatekeepers for the approval of healthcare interventions for pain and of clinical practice guidelines,” they wrote. “Funders are gatekeepers to the allocation of research resources. Research Institutions can foster cultures that promote, support, and incentivise positive behaviours. Editors, publishers and peer reviewers are gatekeepers to the published research literature.
“All have the responsibility to use that power to promote trustworthiness.”
Promoting trust and taking action
In an interview with Massage & Fitness, O’Connell said that he and his colleagues have just gone live with ENTRUST-PE in December 2024, promoting it through papers, social media and art conferences.
“Our finding was just to develop the framework, and we don’t currently have funding beyond that,” O’Connell said. “The idea, I guess, is that we have laid down a marker and started a conversation and that the pain research community can hopefully engage with that: Reflect and make positive change.
“We have no enforcement power. We created factsheets and offer recommendations for a wide range of stakeholders—not just researchers but funders, institutions, regulators and policymakers, editors and publishers, peer reviewers, and learned societies,” he continued. “These are all agents that hold power and that can make change. I am delighted that so far, IASP, [European Pain Federation], and the Australian Pain Society have all officially endorsed ENTRUST-PE. Just this week, we saw the framework referenced in guidance to applicants for national research funding here in the U.K.”
O’Connell clarified that the policymakers are people who work in organizations similar to the First Division Association (FDA) and National Institute for Health and Care Excellence (NICE) in the U.K.
“Gatekeepers are all of us,” he said. “Most researchers hold more than one role in the research ecosystem. We are often researcher, mentor, manager, editors. Many of us sit on grant panels or hold leadership roles in societies, and we all peer review.”
O’Connell reminded that what they are doing is not policework. “A healthy research ecosystem should act to reward scientific excellence, identify and filter out things that fall short,” he said. “In terms of the dark end of this—intentional misconduct—we need a strong line of communication between editors, institutions and also funders to investigate , fairly and transparently, claims of misconduct and take action on them. Action may mean sanctions against researchers. There are lots on unfortunate examples in the wider research world of where institutions have ignored concerns and closed ranks, putting reputation ahead of patient welfare and transparency. We should expect better.”
Dr. Neil O’Connell teaches a workshop on making sense of evidence in research at the 2020 San Diego Pain Summit. (Photo by Nick Ng)
Why does research trustworthiness matter?
O’Connell said that promoting trustworthiness in research boils down to the question, “Why do we do research?” or “What is research for?”
“As human beings, we are pretty bad observers of reality as we see everything through a loaded lens,” he said. “That is one reason we do research. You can view research as ‘the application of process to observation.’”
In other words, that means “the search for truth,” he added.
“That process should afford us more rigour, mechanisms to minimise those biases and transparency,” O’Connell continued. “That is why research is held up as a trustworthy source of information. So the process is king. If we do research to improve knowledge (and in pain, therefore, patient care), then we need to ensure our research meets these standards. Otherwise, research becomes a kind of theatre in which many can build careers and reputations but nothing improves. If we aren’t careful about quality then none of it matters.”
O’Connell and his colleagues are looking for funding to do more research in this niche. “We will keep promoting ENTRUST and hopefully developing it, keep pulling on levers to try to achieve incremental improvements, [and] keep reflecting on what we, as researchers, can do to improve the trustworthiness of our research.” he said.
Nick Ng is the editor of Massage & Fitness Magazine and the managing editor for My Neighborhood News Network.
An alumni from San Diego State University with a bachelor’s in graphic communications, Nick also completed his massage therapy training at International Professional School of Bodywork in San Diego in 2014. In 2021, he earned an associate degree in journalism at Palomar College.
When he gets a chance, he enjoys weightlifting at the gym, salsa dancing, and exploring new areas in the Puget Sound area in Washington state.
