Estimating the Causal Effect of Lower Tidal Volume Ventilation on Survival in Patients with Acute Lung Injury

Acute lung injury (ALI) is a condition characterized by acute onset of severe hypoxemia and bliateral pulmonary infiltrates. ALI patients typically require mechanical ventilation in an intensive care unit. Low tidal volume ventilation (LTVV), a time-varying dynamic treatment regime, has been recommended as an effective ventilation strategy. This recommendation was based on the results of the ARMA study, a randomized clinical trial designed to compare low vs. high tidal volume strategies (ARDSNetwork, 2000) . After publication of the trial, some critics focused on the high non-adherence rates in the LTVV arm suggesting that non-adherence occurred because treating physicians felt that deviating from the prescribed regime would improve patient outcomes. In this paper, we seek to address this controversy by estimating the survival distribution in the counterfactual setting where all patients assigned to LTVV followed the regime. Our estimation strategy is based on Robins’s (1986) G-computation formula and fully Bayesian multiple imputation to handle intermittent missing data