Updating the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials
Goal: To develop and disseminate an updated Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials (CRTs) and two novel implementation guidance documents.
Background and rationale: CRTs differ from individually randomized trials in that they allocate groups of people—rather than individuals—to study interventions. While commonly used to evaluate clinical, health policy, health systems, and public health interventions, CRTs raise complex ethical issues. Published ten years ago, the Ottawa Statement is the only international guidance document specific to CRTs. It has informed the design of many CRTs and influenced policy internationally. However, due to novel CRT designs, the increasing availability of routinely collected data, and emphasis on pragmatic approaches to trial design, patient and other stakeholder engagement, and health equity considerations in trial designs, it is now time to update the Ottawa Statement.
Research aims and methods: Our specific aims are to: (1) conduct conceptual and empirical research to identify gaps in the Ottawa Statement; (2) update the Ottawa Statement to address identified gaps in guidance while incorporating patient and other stakeholder perspectives; (3) develop implementation guidance documents with examples and commentary to facilitate application of the updated Ottawa Statement; and (4) create a research agenda to enable researchers to work collectively on unresolved ethical issues raised by CRTs. Our mixed-methods approach incorporates conceptual and empirical work and involves substantial stakeholder engagement. Empirical work includes a citation analysis of the Ottawa Statement and systematic reviews. This work will inform concurrent ethical analyses, and results from all activities will inform working groups updating the Ottawa Statement, developing two implementation guidance documents, and creating a research agenda.
Expertise: Development of ethics guidance requires an interdisciplinary team. Our nominated PI is a leading expert on the ethics of randomized controlled trials and first author of the Ottawa Statement. Our co-PI is a biostatistician and an expert in CRTs who co-led the development of the Ottawa Statement. Our internationally recognized research team brings together 31 ethicists, knowledge users, methodologists, patient engagement experts, patient partners, and trialists from Africa, Europe, North America, and South America. Our research team has extensive practical experience with CRTs, clinical and ethics guideline development, and patient engagement.
Significance and expected outcomes: The major impact of the proposed work will be internationally applicable ethics guidance for CRTs. Publications will include: (1) an Ottawa Statement citation analysis; (2) systematic reviews of (a) CRTs in low-resource setting, and (b) CRTs in long-term care facilities; (3) the updated Ottawa Statement; (4) implementation guidance documents for (a) low-resource settings and (c) long-term care facilities; and (6) a research agenda.
Charles Weijer (Western University)
Monica Taljaard (Ottawa Hospital Research Institute)
Fernando Althabe (Institute for Clinical Effectiveness and Health Policy, Argentina)
Ariella Binik (McMaster University)
Jamie Brehaut (Ottawa Hospital Research Institute)
Sandra Eldridge (Queen Mary University London, United Kingdom)
Rashida Ferrand (London School of Hygiene and Tropical Health and Health Research Unit, Zimbabwe)
Katie Gillies (University of Aberdeen, United Kingdom)
Bruno Giraudeau (University of Tours, France)
Cory Goldstein (Ottawa Hospital Research Institute)
Jeremy Grimshaw (Ottawa Hospital Research Institute)
Lars Hemkens (University of Basel, Switzerland)
Karla Hemming (University of Manchester, United Kingdom)
Mira Johri (University of Montreal)
Scott Kim (National Institutes of Health, USA)
Emily Largent (University of Pennsylvania, USA)
Jennifer Leese (Ottawa Hospital Research Institute)
Alex London (Carnegie Mellon University, USA)
Olivia Magwood (Bruyère Research Institute)
Susan Marlin (Clinical Trials Ontario)
Lawrence Mbuagbaw (McMaster University)
Susan Mitchell (Harvard University, USA)
Stuart Nicholls (Ottawa Hospital Research Institute)
Jennifer Petkovic (Bruyère Research Institute)
Shaun Treweek (University of Aberdeen, United Kingdom)
Peter Tugwell (Ottawa Hospital Research Institute)
Rieke van der Graaf (UMC Utrecht, The Netherlands)
Vivian Welch (University of Ottawa)
Mary Beaucage (Ontario Renal Network)
Claudia Hampel (Ottawa Hospital)
Maureen Smith (Research Canada)
Ethik-dumping: Koloniales denken in der wissenschaft. Wissenschaft im Brennpunkt, Deutschlandfunk (Germany). December 27, 2020.
Local students heading back to class as COVID-19 case counts tick down. Let’s Talk London with Jess, AM980 News. February 1, 2021.
WHO’s malaria vaccine study represents a “serious breach of international ethical standards." British Medical Journal. February 26, 2020.
WHO accused of conducting vaccine trial without participant consent in three African countries. Gizmodo. February 26, 2020.
Canadian bioethicist calls WHO malaria study involving kids 'serious breach' of standards. CTV News. February 27, 2020.
Bioethicists criticize WHO’s malaria vaccine trial. The Scientist. February 28, 2020.
More evidence needed to inform policy on sending kids back to school. Western News. January 21, 2021.
Here's what medical experts say about the importance of kids returning to school. CTV News. January 21, 2021.
Study needed to determine COVID-19 risks of keeping schools open: researcher. London Free Press. January 22, 2021.
When should kids return to in-person learning? Western University researcher, colleagues finding answers. Global News. January 23, 2021.
Mtande TK, Weijer C, Hosseinipour MC, Taljaard M, Matoga M, Goldstein CE, Nyambalo B, Rosenberg NE. Ethical issues raised by cluster randomised trials conducted in low-resource settings: identifying gaps in the Ottawa Statement through an analysis of the PURE Malawi trial. Journal of Medical Ethics 2019; 45(6): 388-393.
Weijer C, Taljaard M. Ottawa Statement does not impede randomised evaluation of government health programmes. J Med Ethics 2020; 46(1): 31-33.
Taljaard M, Goldstein CE, Giraudeau B, Nicholls SG, Carroll K, Hey SP, Brehaut JC, Jairath V, London AJ, Eldridge SM, Grimshaw JM, Fergusson DA, Weijer C. Cluster over individual randomization: are study design choices appropriately justified? Review of a random sample of trials. Clinical Trials 2020; 17(3): 253-263.
Weijer C, Hemming K, Phillips Hey S, Fernandez Lynch H. Reopening schools safely in the face of COVID-19: Can cluster randomized trials help? Clinical Trials 2021;18(3) :371-376.
Nix HP, Weijer C, Brehaut JC, Forster D, Goldstein CE, Taljaard M. Informed consent in cluster randomised trials: a guide for the perplexed. BMJ Open 2021; 11(9): e054213.
Nix HP, Largent EA, Taljaard M, Mitchell SL, Weijer C. Ethical analysis of vulnerabilities in cluster randomized trials involving people living with dementia in long-term care homes. JAGS: Journal of the American Geriatric Society 2023; 71(2): 588-598.
McIntyre LA, Fergusson DA, McArdle T, Fox-Robichaud A, English SW, Martin C, Marshall J, Cook DJ, Graham ID, Hawken S, McCartney C, Menon K, Saginur R, Seely A, Stiell I, Thavorn K, Weijer C, Iyengar A, Muscedere J, Forster AJ, Taljaard M; Canadian Critical Care Trials Group. FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer's lactate. BMJ Open 2023; 13(2): e067142. [12 pages]
Weijer C. The WHO Malaria Vaccine Trial: a bioethicist responds. Rapid Response. BMJ. March 5, 2020.
Weijer C, Taljaard M. Unnatural experiments. Journal of Medical Ethics Blog. November 28, 2019.
Stepped wedge cluster randomised trials raise important ethical issues. Stepped Wedgehog Blog. March 22, 2021.
Informed consent in cluster randomized trials: a guide for the perplexed. Biomedical Research and Training Institute. Harare, Zimbabwe. February 1, 2022.
Informed consent in cluster randomized trials: a guide for the perplexed. Health Research Board Trials Methodology Research Network. Ireland. February 9, 2022.
Ethical challenges of cluster randomized trials in implementation research. Panel on Equity and Justice in Designing, Funding, and Conducting Implementation Research. World Congress of Bioethics. Switzerland. July 22, 2022.
The ethics of pragmatic trials: common pitfalls and a way forward. Congress of the International Pediatric Nephrology Association. Calgary. September 9, 2022.
Goldstein CE, Beaucage M, Cook C, Taljaard M, Weijer C. The Ottawa Statement implementation guidance document for CRTs in the Hemodialysis setting (OSimpleHD): ethics guidance for researchers and research ethics committees co-developed with patient partners. Gardener’s Grove 2023. March 30, 2023.
Updating the Ottawa Statement. Cluster Randomized Trials Pre-Workshop Meeting. France. June 20, 2023.
Ethical issues in cluster randomized trials. INSERM Workshop 274: Cluster Randomized Trials and Within Person Trials: Statistical, Practical, and Ethical Issues. France. June 21, 2023.