Cluster identification, selection, and description in cluster randomized crossover trials: the PREP-IT trials

Abstract

Background In cluster randomized crossover (CRXO) trials, groups of participants (i.e., clusters) are randomly allocated to receive a sequence of interventions over time (i.e., cluster periods). CRXO trials are becoming more comment when they are feasible, as they require fewer clusters than parallel group cluster randomized trials. However, CRXO trials have not been frequently used in orthopedic fracture trials and represent a novel methodological application within the field. To disseminate the early knowledge gained from our experience initiating two cluster randomized crossover trials, we describe our process for the identification and selection of the orthopedic practices (i.e., clusters) participating in the PREP-IT program and present data to describe their key characteristics. Methods The PREP-IT program comprises two ongoing pragmatic cluster randomized crossover trials (Aqueous-PREP and PREPARE) which compare the effect of iodophor versus chlorhexidine solutions on surgical site infection and unplanned fracture-related reoperations in patients undergoing operative fracture management. We describe the process we used to identify and select orthopedic practices (clusters) for the PREP-IT trials, along with their characteristics. Results We identified 58 potential orthopedic practices for inclusion in the PREP-IT trials. After screening each practice for eligibility, we selected 30 practices for participation and randomized each to a sequence of interventions (15 for Aqueous-PREP and 20 for PREPARE). The majority of orthopedic practices included in the Aqueous-PREP and PREPARE trials were situated in level I trauma centers (100% and 87%, respectively). Orthopedic practices in the Aqueous-PREP trial operatively treated a median of 149 open fracture patients per year, included a median of 11 orthopedic surgeons, and had access to a median of 5 infection preventionists. Orthopedic practices in the PREPARE trial treated a median of 142 open fracture and 1090 closed fracture patients per year, included a median of 7.5 orthopedic surgeons, and had access to a median of 6 infection preventionists. Conclusions The PREP-IT trials provide an example of how to follow the reporting standards for cluster randomized crossover trials by providing a clear definition of the cluster unit, a thorough description of the cluster identification and selection process, and sufficient description of key cluster characteristics. Trial registration Both trials are registered at ClinicalTrials.gov (A-PREP: NCT03385304 December 28, 2017, and PREPARE: NCT03523962 May 14, 2018).

A pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solutions in open fractures (Aqueous-PREP): statistical analysis plan

“…The study is a pragmatic, multicenter, open-label, randomized multiple period cluster crossover trial. We defined clusters as orthopedic practices within participating hospitals, with each participating hospital having only one participating orthopedic practice [ 13 ]. The intervention periods are approximately 2 months in length.…”

“…We will report the number of clusters (orthopedic practices) screened, included, and excluded in a flow diagram. The number of clusters excluded by reason has been reported previously [ 13 ]. Cluster randomization allocation will be included in the flow diagram, and adherence with treatment allocation during the run-in period by cluster will be summarized using percentages.…”

Managing work flow in high enrolling trials: The development and implementation of a sampling strategy in the PREPARE trial

“…The clinical sites participating in the PREPARE trial are mostly level one trauma centers that treat a high volume of open fractures and closed fracture [ 8 ]. For example, the lead clinical site in the PREPARE trial, R Adams Shock Trauma Center, operatively treats approximately 400 open fracture patients and 1600 closed fracture patients each year.…”

A Pragmatic Randomized trial Evaluating Pre-operative aqueous antiseptic skin solutions in open fractures (Aqueous-PREP): Statistical Analysis Plan

“…The number of clusters excluded by reason has been reported previously. 13 Cluster randomization allocation will be included in the ow diagram, and adherence with treatment allocation during the run-in period by cluster will be summarized using percentages.…”

“…Speci c details on characteristics of participating clusters, orthopaedic characteristics, and surgical infection prevention information in the Aqueous-PREP trial have been previously published. 13 4.6 Participant Demographics, Fracture Characteristics, and Descriptions of Surgical and Perioperative Care…”