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.