A randomization strategy for a cluster-randomized controlled trial with variable operating room availability

A single-center, open-label, pragmatic, non-inferiority, cluster randomized controlled trial was conducted to compare the clinical outcomes of two diagnostic bronchoscopy approaches, Platform A and Platform B. A cluster was defined as an operating room (OR) day. The expected allocation ratio at the cluster level was 1:1 between Platform A and Platform B. The resources available for this trial included one Platform A, one Platform B, two ORs available for two days a week, and one OR available for the other three days. When one platform was randomly assigned to one OR, the other platform was placed in the other OR. Due to limitations in OR and bronchoscopy platform availability precluding individual patient randomization, a stratification strategy was proposed to randomize ORs to a given platform. A simulation with 1000 replicates was performed to assess balance of assignments, using imbalance (defined as the difference/imbalance in the number of patients enrolled between Platform A and Platform B) and its standard deviation as evaluation metrics. At day 150 (210 assignments), a permuted-block randomization method, incorporating stratification by weekdays, reduced both imbalance and variation (mean = 0.044, standard deviation (SD) = 1.110, median = 0, range = (-4, 4)), compared to a permuted-block randomization method (mean = -0.238, SD = 7.064, median = 0, range = (-24, 22)). We further explored an alternative strategy: stratification by OR availability. This evaluation analysis revealed a greater reduction in imbalance, with a range of -2 and 2 (mean = -0.006, SD = 0.690, median = 0). Our innovative study designs, incorporating a permuted-block randomization method stratified by OR availability, effectively reduced the imbalance assignments and optimized allocation of resources. Trial registration ClinicalTrials.gov registration (NCT05705544) for RELIANT on January 30, 2023. ClinicalTrials.gov registration (NCT06654271) for RELIANT 2 on January 12, 2024.