Moving Beyond Mortality : Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
BACKGROUND: 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.
METHODS: A 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.
RESULTS: In 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.
CONCLUSIONS: The 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 78(2024), 2 vom: 17. Feb., Seite 259-268 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Howard-Anderson, Jessica [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 29.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/cid/ciad576 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Moving Beyond Mortality |b Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia |
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| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: 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 | ||
| 520 | |a METHODS: A 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 | ||
| 520 | |a RESULTS: In 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 | ||
| 520 | |a CONCLUSIONS: The 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a clinical trials | |
| 650 | 4 | |a desirability of outcome ranking | |
| 650 | 4 | |a drug development | |
| 650 | 4 | |a hospital-acquired bacterial pneumonia | |
| 650 | 4 | |a ventilator-associated bacterial pneumonia | |
| 650 | 7 | |a Linezolid |2 NLM | |
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| 700 | 1 | |a Geres, Holly |e verfasserin |4 aut | |
| 700 | 1 | |a Holland, Thomas L |e verfasserin |4 aut | |
| 700 | 1 | |a Doernberg, Sarah B |e verfasserin |4 aut | |
| 700 | 1 | |a Chambers, Henry F |e verfasserin |4 aut | |
| 700 | 1 | |a Fowler, Vance G |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Evans, Scott R |e verfasserin |4 aut | |
| 700 | 1 | |a Boucher, Helen W |e verfasserin |4 aut | |
| 700 | 0 | |a Antibacterial Resistance Leadership Group |e verfasserin |4 aut | |
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| 700 | 1 | |a Cosgrove, Sara |e investigator |4 oth | |
| 700 | 1 | |a Doernberg, Sarah |e investigator |4 oth | |
| 700 | 1 | |a Evans, Scott |e investigator |4 oth | |
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| 700 | 1 | |a Gopinath, Ramya |e investigator |4 oth | |
| 700 | 1 | |a Kim, Peter |e investigator |4 oth | |
| 700 | 1 | |a Natarajan, Mukil |e investigator |4 oth | |
| 700 | 1 | |a Needles, Mark |e investigator |4 oth | |
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| 700 | 1 | |a Waack, Ursula |e investigator |4 oth | |
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