A new method to address unmeasured confounding of mortality in observational studies

INTRODUCTION: The prior event rate ratio (PERR) overcomes “unmeasured confounding” by adjusting study outcomes for all confounding (measured and unmeasured) by comparing exposed to unexposed cohort outcomes prior to study entry when neither group is receiving treatment. However, PERR cannot address “unmeasured confounding” of death since prior events cannot occur. METHODS: This study's goal is to determine whether a new method, built on the concepts that led to the PERR development, reliably overcomes unmeasured confounding for death. In contrast to the PERR, which precedes study onset, the new mortality analysis uses exposed and unexposed cohorts, not taking the treatment medication, at the end of the study. It is called the post‐treated event rate ratio (PTERR). RESULTS: Theoretical and simulation studies were used to evaluate the likelihood for reliable results using of this new analytic strategy. Also, prior empiric studies, which used both the UK GPRD and THIN databases to examine and validate the PERR method, were used to ascertain the validity of the PTERR method. CONCLUSION: In the aggregate the results provide strong evidence that the PTERR method to evaluate unmeasured confounding will be a valuable analytic tool.