Individual consent in cluster randomised trials for non-pharmaceutical interventions: going beyond the Ottawa statement

ABSTRACT

This paper discusses the issue of overriding the right of individual consent to participation in cluster randomised trials (CRTs). We focus on CRTs testing the efficacy of non-pharmaceutical interventions. As an example, we consider school closures during the COVID-19 pandemic. In Norway, a CRT was promoted as necessary for providing the best evidence to inform pandemic management policy. However, the proposal was rejected by the Norwegian Research Ethics Committee since it would violate the requirement for individual informed consent. This sparked debate about whether ethics stand in the way of evidence-based health policy, since the Norwegian Research Ethics law’s strict requirements for individual consent make it practically impossible to carry out CRTs of public health interventions. We argue that, in the case of the school closure trial, the suggested CRT would not have eliminated an epistemic gap and thus would not have justified the violation of consent rights. First, we focus on the methodological challenges to estimating quantifiable effects of school closures in the specific case of an airborne infectious disease. Second, in line with Evidential Pluralism, we highlight the value of alternative lines of evidence for informing school closure policy in a pandemic. In general, we propose that a trial requiring the waiver of participants’ consent rights must be highly likely to eliminate an epistemic gap. We elaborate on the practical aspects of this criterion and discuss the potential advantages of adding it to the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials.

KEYWORDS:

• COVID-19
• evidence-based policy
• infectious disease management
• Ottawa statement on the ethical design and conduct of cluster randomized trials
• Evidential pluralism

Acknowledgements

We are grateful to an anonymous reviewer and to Alexandra Trofimov for insightful and helpful comments.

Disclosure statement

Marissa LeBlanc reports the receipt of a speaker fee from MSD for activities unrelated to this work.

Notes

1. The Monographs programme of the International Agency for Research on Cancer (IARC), which conducts evaluations of carcinogenicity, provides an example of an agency whose methodology conforms closely to the principles of Evidential Pluralism (Williamson, 2019b). Evidential Pluralism should arguably also be applied to the evaluation of pharmaceutical interventions (Aronson et al., 2018; Maziarz & Stencel, 2022; Park et al., 2023). Currently, however, drug approval agencies only systematically scrutinise mechanistic evidence in certain contexts. One such context is the evaluation of biosimilar medicines, where mechanistic studies are routinely considered in place of clinical studies. Another is the US FDA Accelerated Approval Program: instead of demonstrating that a medicine directly induces a clinical outcome, the program evaluates whether there is some mechanism that leads to the clinical outcome via a surrogate endpoint, i.e. a mediating variable.

Additional information

Funding

Jon Williamson’s research is supported by Leverhulme Trust grant [Reference: RPG-2022-336].