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Exploration of a Potential DOOR Endpoint for Complicated Intra-Abdominal Infections Using Nine Registrational Trials for Antibacterial Drugs

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April 19, 2023

Tori Kinamon, Ramya Gopinath, Ursula Waack, Mark Needles, Daniel Rubin, Deborah Collyar, Sarah B Doernberg, Scott Evans, Toshimitsu Hamasaki, Thomas L Holland, Jessica Howard-Anderson, Henry Chambers, Vance G Fowler, Jr, Sumati Nambiar, Peter Kim, Helen W Boucher


Background: Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intraabdominal infection (cIAI).

Methods: Initially, we applied an a priori DOOR prototype to electronic patient-level data from nine Phase 3 noninferiority trials for cIAI submitted to the FDA between 2005-2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator.

Results: Three key findings informed the cIAI-specific DOOR endpoint: 1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; 2) infectious complications of cIAI were diverse; and 3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment vs. comparator.

Conclusions: We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease-specific DOOR endpoints.

Keywords: DOOR; Intraabdominal infection; antimicrobial therapy; clinical trials; endpoints.

Source: https://pubmed.ncbi.nlm.nih.gov/37073571/