Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia (in EN)
Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation.
MethodsA multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses.
ResultsIn both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%−55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%–52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid.
ConclusionsThe HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR.
- Research Organization:
- Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- DOE Contract Number:
- SC0014664
- OSTI ID:
- 2582313
- Journal Information:
- Clinical Infectious Diseases, Journal Name: Clinical Infectious Diseases Journal Issue: 2 Vol. 78; ISSN 1058-4838
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- EN
Similar Records
Exploration of a Potential DOOR Endpoint for Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia Using Six Registrational Trials for Antibacterial Drugs