Unblinding risk score: a measure of risk for guessing the treatment group in blinded studies

Music City Center 

Randomized double-blind clinical trials are considered the "gold standard" for evaluating the effects of a new intervention. Traditionally, only the treatment assignment is blinded to the investigator and sponsor. However, differences in response variables between the investigational and control arms is typically hypothesized. If such differences are large, awareness of the response variables could reveal the treatment assignment and potentially introduce bias into the study. To mitigate this, responses are sometimes blinded to prevent reverse guessing, but this complicates study monitoring. However, are such measures really required to protect study integrity? We propose an unblinding risk score (URS) to quantify the risk that blinded site or Sponsor personnel could correctly guess the treatment assignment based on an individual patient's efficacy response. Our findings are applied to several published studies to demonstrate how the URS can evaluate unblinding risk, and we demonstrate an interactive tool built in R Shiny tool to help study teams assess this risk before deciding to mask or not mask the efficacy data.

Clinical trials

data masking

unblinding

risk assessment

randomized double-blinded placebo-controlled studies

unblinding risk 

Biopharmaceutical Section