Application of a Novel Desirability of Outcome Ranking Endpoint Incorporating a Framework for Resistance Assessment and Microbiologic Evaluation in Antibiotic Trials: A Proof-of-Concept in a Post Hoc Analysis of the BALANCE Trial.

Background: Desirability of Outcome Ranking (DOOR) with Response Adjusted for Duration of Antibiotic Risk (RADAR) has been suggested as an outcome for antibiotic duration trials. An endpoint incorporating a measure of antimicrobial resistance may better reflect trade-offs between different antibiotic strategies. Methods: We constructed a novel endpoint, DOOR-FRAME (Framework for Resistance Assessment and Microbiologic Evaluation), and applied it as a proof-of-concept in a post hoc analysis of the BALANCE trial comparing 7- versus 14-day antibiotic duration for uncomplicated non- Results: Two hundred seventy-one participants were included. The DOOR distributions were similar between the 7- and 14-day groups, with PI of 46.8% (95% CI 40.4%-53.2%) using DOOR alone. Nine (6.9%) and 12 (8.5%) patients in the 7 and 14-day group respectively had ARO/CDI within 180 days. Probabilistic index was 53.6% (95% CI 46.7%-60.4%) with DOOR-RADAR and 47.4% (95% CI 40.9%-53.8%) with DOOR-FRAME. Conclusions: There were no significant differences in DOOR outcomes at 180 days between patients with uncomplicated BSI treated with 7 versus 14-day antibiotic duration. Incorporating a novel measure of antimicrobial resistance did not change interpretation of the trial.