By G. Owen Schaefer.

Sorting and categorization is a classic and sometimes entertaining parlor game. Is a taco a sandwich? Is a couch a chair? Are calculators computers? Other times, though, the stakes are higher, particularly when classification has moral or legal implications – such as the question of whether corporations are people, or whether soy milk can truly be called milk. In such cases, categorizing a certain entity or activity might change what we are or are not permitted to do, the laws that apply, and/or the ethical frameworks that are most applicable.

I examine just one such case of weighty classification in “If it walks like a duck…: Monitored Emergency Use of Unregistered and Experimental Interventions (MEURI) is research”. MEURI is an ethical framework developed at the WHO that emerged out of the 2014 Ebola outbreak and was reinvigorated during the COVID-19 pandemic, under which unproven interventions in public health emergencies could be delivered outside the context of medical research. The idea is that in some circumstances, rigorous clinical trials are impracticable to set up or run properly. A strict framework that demanded unproven interventions only be provided in a research setting would potentially preclude some patients from getting treatments that are in their best interests. At the same time, lack of oversight and guidance over provision of unproven interventions could lead to wide-scale provision of interventions that are at best useless and at worst harmful, while squandering the opportunity to learn and shift interventions from unproven to proven.

Why is the question of whether or not MEURI is research so important? Partly, this is a legal or regulatory issue. In most jurisdictions, there are special rules that govern the conduct and oversight of human subjects research, including ethics board review, provision of detailed informed consent (or a waiver of that), and requirements of sufficient evidence base concerning prospect of benefit (either to the participant or society). Partly, it is ethical, as these legal rules are underpinned by well-established ethical principles fashioned to protect participants from abuse or exploitation while promoting valuable knowledge-generation.

Moreover, this is a practical matter: MEURI is motivated largely by the practical challenges in conducting rigorous research during a public health emergency. Some of these challenges come from legal compliance, while others relate to ensuring sound design and scientific methodology. MEURI is intended to be a practicable alternative to such onerous requirements that come with conducting research. When research is impracticable, MEURI offers a rigorous and principled ethical framework for deploying unproven interventions.

However, MEURI falls victim to its own complexity. In attempting a rigorous and principled framework, it ends up replicating many of the key aspects of research, such that to deny MEURI is a form of research is to make a distinction without a difference.

Firstly, MEURI does not entirely eschew the goal of knowledge-generation; one of the four challenges motivating MEURI is that “there is substantial need to generate evidence when unproven interventions are used,” while another concerns the need to ensure clinical trials are not stymied by uncontrolled provision of unproven interventions. To be sure, patient benefit remains front and center to the MEURI framework, but this is diluted by the attention paid (and requirements flowing from) the need for MEURI to contribute to evidence.

Secondly, pursuant to this evidence-generation goal, MEURI includes requirements to monitor and share relevant outcomes and data. While such data use may be distinct from research interventions, it falls more naturally into a form of prospective observational research, where plans for data gathering and analysis are circumscribed in advance even if an intervention is not being provided in a randomized controlled trial.

Thirdly, MEURI requires a detailed protocol (including background, scientific justification, risks and benefits, and data sharing plans) that should be vetted and approved by a relevant committee – with the ‘default’ in fact being a research ethics committee. Making use of a research ethics committee for this purpose is natural, since they are well-designed and trained to evaluate just the sort of protocols that MEURI requires. But it also highlights the high degree of overlap between MEURI and standard research practices.

Finally, in practice, during the COVID-19 pandemic many published uses of MEURI in fact fell explicitly into a research ethics framework. A protocol in Tunisia explicitly referred to as “MEURI” was given a formal study number, list of primary and secondary outcomes, inclusion/exclusion criteria and other features one would expect from a research study. An Argentinian study with “MEURI” in its title was registered in a national research database, ethics committee approval was obtained, individuals consistently referred to as ‘participants’ and ‘subjects’, and so forth. And a Pakistani study with similar MEURI references received IRB approval, was registered on clinicaltrials.gov, and was declared to have been conducted in accordance with the Declaration of Helsinki.

The upshot is that MEURI is, for all intents and purposes, a form of research. This is not necessarily problematic in itself; the pandemic has revealed that much more research may be feasible in low-resource settings than previously conjectured. However, some circumstances where research is infeasible may remain. In such cases, complying with the MEURI framework won’t be of much help, since one must still put together a design just as rigorous and detailed and with similar oversight as a research protocol.

Further work, then, is needed on systems that are truly practicable alternatives to providing unproven interventions when research is infeasible. I and some colleagues have proposed just one such framework elsewhere, called the “Professional Oversight of Emergency-Use Interventions and Monitoring Systems” (POEIMS), and further inspiration may be drawn from approaches like the IDEAL framework for surgical innovation. This work should take care, though, that oversight and governance not become so complex and involved that it is self-defeating as a practicable alternative to research.

Paper title: If it walks like a duck…: Monitored Emergency Use of Unregistered and Experimental Interventions (MEURI) is research

Authors: G. Owen Schaefer

Affiliations: Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore

Competing interests: None declared

Social media accounts of post author: Twitter: @G_Owen_Schaefer