Cory Goldstein

Cluster randomization is an increasingly important trial design that can help advance the agenda of the pragmatic trial and provide essential information about the effectiveness and comparative effectiveness of interventions used routinely in medical practice. In addition to the parallel-arm design, cluster cross-over and stepped wedge designs are becoming increasingly popular. When such designs are embedded within routine clinical practice with waivers of informed consent, they have several methodological and logistical advantages over traditional patient randomized designs. However, these trials raise ethical issues that challenge researchers, research ethics committees, regulators, and sponsors as they seek to responsibly fulfill their respective roles. This workshop will use the FLUID and TRACTION trials to illustrate these issues, stimulate discussion, and inform the development of proposed solutions. FLUID is an ongoing pragmatic comparative effectiveness cluster cross-over trial currently taking place ─ with waived consent ─ at hospitals in Ontario. FLUID compares the effects of two commonly used resuscitation fluids: Normal Saline versus Ringer’s Lactate, on death and hospital readmissions. TRACTION is a pragmatic trial currently being planned at hospitals in Ontario and Manitoba, to evaluate whether a hospital policy of universal use of tranexamic acid during major surgeries safely reduces red blood cell transfusions. The methodological and ethical implications of cluster versus individual randomization will be discussed. Both FLUID and TRACTION raise several challenging ethical issues: What is an appropriate justification for cluster randomization? When individual-level interventions are implemented institution-wide as a policy in a cluster randomized trial, may one proceed without patient consent? Do patients need to be notified about the trial; if so, how? How should risk be evaluated given prior efficacy and safety data in other settings? After a series of presentations by trialists, methodologists and ethicists, we will engage in interactive discussions with the audience using a web-based audience response system.