Exploration of a Potential DOOR Endpoint for Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia Using Six Registrational Trials for Antibacterial Drugs

Authors

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

Publication Date

7-19-2024

Journal

Clinical Infectious Diseases

Abstract

BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

METHODS: Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator.

RESULTS: DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Although infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar.

CONCLUSIONS: Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design.

Keywords

Humans, Pneumonia, Ventilator-Associated, Anti-Bacterial Agents, Pneumonia, Bacterial, Male, Healthcare-Associated Pneumonia, Female, United States, Clinical Trials as Topic, Cross Infection, Treatment Outcome, Middle Aged, United States Food and Drug Administration, Aged

Comments

Supplementary Materials

PMID: 38527855