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

Tori Kinamon, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Ursula Waack, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Mark Needles, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Daniel Rubin, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Deborah Collyar, Patient Advocates in Research, Danville, CA, USA.
Sarah B. Doernberg, Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Scott R. Evans, Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, D.C., USA.
Toshimitsu Hamasaki, Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, D.C., USA.
Thomas L. Holland, Department of Medicine, Duke University Medical Center, Durham, NC  USA.
Jessica Howard-Anderson, Antibacterial Resistance Leadership Group, Durham, NC, USA.
Henry Chambers, Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Vance G. Fowler, Department of Medicine, Duke University Medical Center, Durham, NC  USA.
Sumati Nambiar, Antibacterial Resistance Leadership Group, Durham, NC, USA.
Peter Kim, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Helen W. Boucher, Antibacterial Resistance Leadership Group, Durham, NC, USA.
Ramya Gopinath, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.

Document Type

Journal Article

Publication Date

3-25-2024

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

DOI

10.1093/cid/ciae163

Keywords

DOOR; antimicrobial therapy; clinical trials; hospital-acquired bacterial pneumonia; ventilator-associated bacterial pneumonia

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 4,000 participants enrolled in six registrational trials for HABP/VABP submitted to the FDA between 2005-2022, 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. Though 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.

Department

Biostatistics and Bioinformatics

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