The increasing use of cluster randomised trials in low-resource settings raises unique ethical issues. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomised Trials is the first international ethical guidance document specific to cluster trials, but it is unknown if it adequately addresses issues in low-resource settings. In this paper, we seek to identify any gaps in the Ottawa Statement relevant to cluster trials conducted in low-resource settings. Our method is (1) to analyse a prototypical cluster trial conducted in a low-resource setting (PURE Malawi trial) with the Ottawa Statement; (2) to identify ethical issues in the design or conduct of the trial not captured adequately and (3) to make recommendations for issues needing attention in forthcoming revisions to the Ottawa Statement. Our analysis identified six ethical aspects of cluster randomised trials in low-resource settings that require further guidance. The forthcoming revision of the Ottawa Statement should provide additional guidance on these issues: (1) streamlining research ethics committee review for collaborating investigators who are affiliated with other institutions; (2) the classification of lay health workers who deliver study interventions as health providers or research participants; (3) the dilemma experienced by investigators when national standards seem to prohibit waivers of consent; (4) the timing of gatekeeper engagement, particularly when researchers face funding constraints; (5) providing ancillary care in health services or implementation trials when a routine care control arm is known to fall below national standards and (6) defining vulnerable participants needing protection in low-resource settings.
- research ethics
- clinical trials
- policy guidelines/inst. review boards/review cttes
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Contributors TKM and CW conceptualised the paper. TKM wrote the first draft, and CW edited and rewrote sections of the next draft. All other authors provided comments on subsequent drafts of the paper. All authors approved the final paper.
Funding TKM is a SARETI scholar funded by a Global Forum on Bioethics in Health Research fellowship, Wellcome Trust grant number 211061/Z/18/Z. This work is also supported by the Canadian Institutes of Health Research through the Project Grant competition (competitive, peer-reviewed), award number PJT-153045. CW holds the Canada Research Chair in Bioethics at Western University. NER is supported by the National Institutes of Health through R00 MH104154 and P30 AI50410.
Competing interests CW receives consulting income from Eli Lilly and Company Canada.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement This article is argument-based, so there are no unpublished data to be shared.
Patient consent for publication Not required.
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