Antibiotic rotation strategies to reduce antimicrobial resistance in Gram-negative bacteria in European intensive care units: study protocol for a cluster-randomized crossover controlled trial

Table 3 Methodological characteristics and key points

Study design feature	Advantages	Disadvantages	Remarks
Cluster allocation	Prevents allocation bias	Susceptible to case mix fluctuations in time	Prevented by adequate intervention period length
Cluster allocation	Prevents between-intervention correlation as compared with individual randomization	Creates cluster correlation of outcomes	Will be accounted for in analysis
Open treatment design	Transparency in patient treatment	Different treatment adherence between different preferred antibiotics	Does not differ between interventions
Pre-intervention control period	Enables comparison with standard care. Enables time trend analysis for time-dependent increase in prevalence	No control group parallel in time	Comparable parallel groups/intensive care units (ICUs) not available, are expected to have higher heterogeneity in ICU characteristics than within-ICU comparisons using a crossover design
Crossover	Intervention comparison within ICUs equals out differences that influence outcome	Increases trial time-span and effect of baseline resistance increases over time	Addressed with time-trend analysis using pre-intervention control period

ISSN: 1745-6215