Gaps in the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials: a citation analysis reveals a need for updated ethics guidelines

Cory E Goldstein; Jessica du Toit; Nicholas B Murphy; Stuart G Nicholls; Julia F Shaw; Fernando Althabe; Ariella Binik; Jamie Brehaut; Sandra Eldridge; Rashida A Ferrand; Katie Gillies; Bruno Giraudeau; Rieke van der Graaf; Lars G Hemkens; Karla Hemming; Mira Johri; Scott Y H Kim; Emily Largent; Alex John London; Lawrence Mbuagbaw; Susan L Mitchell; Maureen Smith; Peter Tugwell; Shaun Treweek; Vivian A Welch; Monica Taljaard; Charles Weijer

doi:10.1186/s41073-025-00166-y

Gaps in the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials: a citation analysis reveals a need for updated ethics guidelines

Res Integr Peer Rev. 2025 Jun 18;10(1):10. doi: 10.1186/s41073-025-00166-y.

Authors

Cory E Goldstein^{1

2}, Jessica du Toit³, Nicholas B Murphy^{4

5}, Stuart G Nicholls^{6

7}, Julia F Shaw^{6

8}, Fernando Althabe⁹, Ariella Binik¹⁰, Jamie Brehaut^{6

8}, Sandra Eldridge¹¹, Rashida A Ferrand^{12

13}, Katie Gillies¹⁴, Bruno Giraudeau^{15

16}, Rieke van der Graaf¹⁷, Lars G Hemkens^{18

19

20}, Karla Hemming²¹, Mira Johri^{22

23}, Scott Y H Kim²⁴, Emily Largent²⁵, Alex John London²⁶, Lawrence Mbuagbaw²⁷, Susan L Mitchell²⁸, Maureen Smith²⁹, Peter Tugwell⁶, Shaun Treweek¹⁴, Vivian A Welch^{8

30}, Monica Taljaard^{6

8}, Charles Weijer^{4

5

31}

Affiliations

¹ Methodological and Implementation Research Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. cogoldstein@ohri.ca.
² School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. cogoldstein@ohri.ca.
³ Department of Clinical and Organizational Ethics, The University Health Network, Toronto, ON, Canada.
⁴ Department of Medicine, Western University, London, ON, Canada.
⁵ Department of Philosophy, Western University, London, ON, Canada.
⁶ Methodological and Implementation Research Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁷ Office for Patient Engagement in Research Activity, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁸ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁹ Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina.
¹⁰ Department of Philosophy, McMaster University, Hamilton, ON, Canada.
¹¹ Pragmatic Clinical Trials Unit, Barts and The London, School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
¹² Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
¹³ The Health Research Unit Zimbabwe, Biomedical Research and Training Institute, Harare, Zimbabwe.
¹⁴ Aberdeen Centre for Evaluation, University of Aberdeen, Aberdeen, UK.
¹⁵ Université de Tours, Université de Nantes, INSERM SPHERE U1246, Tours, France.
¹⁶ INSERM CIC1415, CHRU de Tours, Tours, France.
¹⁷ Department of Bioethics and Health Humanities, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Pragmatic Evidence Lab, Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel, University of Basel, Basel, Switzerland.
¹⁹ Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
²⁰ Meta-Research Innovation Center at Stanford, Stanford University, Stanford, CA, USA.
²¹ Institute of Applied Healthcare Research, University of Birmingham, Birmingham, UK.
²² Centre de Recherche du CHUM, Montreal, QC, Canada.
²³ Département de Gestion, d'évaluation, Et de Politique de Santé, École de Santé Publique de L'Université de Montréal, Montreal, QC, Canada.
²⁴ Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
²⁵ Department of Medical Ethics and Health Policy, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
²⁶ Department of Philosophy, Carnegie Mellon University, Pittsburgh, PA, USA.
²⁷ Biostatistics Unit, St Joseph's Healthcare, Hamilton, ON, Canada.
²⁸ Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.
²⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³⁰ Bruyère Research Institute, Ottawa, ON, Canada.
³¹ Department of Epidemiology & Biostatistics, Western University, London, ON, Canada.

Abstract

Background: Although commonly used to evaluate health interventions, cluster randomized trials raise difficult ethical issues. Recognizing this, the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, published in 2012, provides 15 recommendations to address ethical issues across seven domains. But due to several developments in the design and implementation of cluster randomized trials, there are new issues requiring guidance. To inform the forthcoming update of the Ottawa Statement, we aimed to identify any gaps in the Ottawa Statement discussed within the literature.

Methods: We searched Google Scholar, Scopus, and Web of Science using the 'cited by' function on 11 November 2022.We included all types of publications, including articles, book chapters, commentaries, editorials, ethics guidelines, theses and trial-related publications (i.e., primary reports, protocols, and secondary analyses), that cited and engaged with the Ottawa Statement, the Ottawa Statement précis, or one or more of its four background papers. Data were extracted by four reviewers working in rotating pairs. Reviewers captured relevant text verbatim and recorded whether it reflected a gap relating to one or more of the Ottawa Statement domains. Using a thematic analysis approach, semantic coding was used to summarize the content of the data into distinct gaps within the Ottawa Statement domains, which was subsequently expanded in an inductive manner through discussion.

Results: The qualitative analysis of the text from 53 articles resulted in the identification of 24 distinct gaps in the Ottawa Statement: 4 gaps about justifying the cluster randomized design; 2 gaps about research ethics committee review; 3 gaps about identifying research participants; 4 gaps about obtaining informed consent; 3 gaps about gatekepeers; 6 gaps about assessing benefits and harms; 1 gap about protecting vulnerable participants; and 1 gap about equity-related issues in cluster randomized trials.

Conclusion: Identifying 24 gaps reveals a need to update the Ottawa Statement. Alongside additional gaps identified in ongoing empirical work and through engagement with our patient and public partners, the gaps identified through this citation analysis should be considered in the forthcoming Ottawa Statement update.

Keywords: Benefit-harm assessment; Citation analysis; Ethics guidelines; Informed consent; Research ethics; Research ethics committee review; Vulnerability.

Grants and funding

PJT-479757/CAPMC/ CIHR/Canada