Challenges in the design and analysis of a factorial-design cluster randomised trial

Introduction Optimising sedation quality in mechanically ventilated intensive care patients is important because excessive sedation is associated with increased hospital acquired infections, longer intensive care (ICU) and hospital stay, and possibly higher mortality. The Development and Evaluation of Strategies to Improve Sedation Quality in InTensive Care (DESIST) study aims to optimise sedation practice. Here we focus on the study design, statistical analysis plan, performing the analysis and issues that occurred. DESIST randomised eight ICUs in pairs to four different combinations of sedation-related quality improvement interventions. The primary outcome assessed optimum sedation within each 12 hour nursing shift (referred to as a DESIST care period). This resulted in a three-level hierarchical data structure: DESIST care periods within admissions, within ICU.