Estimating the impact post randomization changes in staff behavior in infection prevention trials: a mathematical modeling approach.

BACKGROUND: Randomized controlled trials (RCTs) of behavior-based interventions are particularly vulnerable to post-randomization changes between study arms. We assess the impact of such a change in a large, multicenter study of universal contact precautions to prevent infection transmission in intensive care units.

METHODS: We construct a stochastic mathematical model of methicillin-resistant Staphylococcus aureus (MRSA) acquisition in a simulated 18-bed intensive care unit (ICU). Using parameters from a recent study of contact precautions that reported a post-randomization change in contact rates, with fewer visits observed in the treatment arm, we explore the impact of several possible interpretations of this change on MRSA acquisition rates.

RESULTS: Scenarios where contact precautions resulted in less patient visitation resulted in a mean decrease in MRSA acquisition rate of 37%, accounting for much of the effect reported in the trial.

CONCLUSIONS: Behavior changes that impact the contact rate have the potential to drastically alter the results of RCTs in infection control settings. Careful monitoring for these changes, and an assessment of which changes will likely have the greatest impact on the study before the study begins are both recommended.