{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:22:55Z","timestamp":1780417375049,"version":"3.54.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI104681"],"award-info":[{"award-number":["UM1AI104681"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01-AI165671"],"award-info":[{"award-number":["1R01-AI165671"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"US Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006229","name":"Oak Ridge Institute for Science and Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000015","name":"US Department of Energy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Antibacterial Research Leadership Group"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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%\u00ad\u221255.3%). 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%\u201352.6%). 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciad576","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T06:51:42Z","timestamp":1695451902000},"page":"259-268","source":"Crossref","is-referenced-by-count":19,"title":["Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9924-0458","authenticated-orcid":false,"given":"Jessica","family":"Howard-Anderson","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine , Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimitsu","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University , Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiao","family":"Dai","sequence":"additional","affiliation":[{"name":"Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University , Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Collyar","sequence":"additional","affiliation":[{"name":"Patient Advocates in Research , Danville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rubin","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration , Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumathi","family":"Nambiar","sequence":"additional","affiliation":[{"name":"Johnson and Johnson , Raritan, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tori","family":"Kinamon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Leister-Tebbe","sequence":"additional","affiliation":[{"name":"Pfizer Inc , Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Hill","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Geres","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L","family":"Holland","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center , Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Duke University School of Medicine , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B","family":"Doernberg","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of California , SanFrancisco, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry F","family":"Chambers","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of California , SanFrancisco, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Vance G","family":"Fowler","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center , Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Duke University School of Medicine , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R","family":"Evans","sequence":"additional","affiliation":[{"name":"Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University , Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen W","family":"Boucher","sequence":"additional","affiliation":[{"name":"Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts University School of Medicine"},{"name":"Tufts Medicine , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Antibacterial Resistance Leadership Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Boucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cosgrove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Doernberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshi","family":"Hamasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Holland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Howard-Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vance","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumati","family":"Nambiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ephraim","family":"Tsalik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramya","family":"Gopinath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukil","family":"Natarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Needles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Waack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Collyar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"2024092200004852700_ciad576-B1","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1093\/cid\/ciw353","article-title":"Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society","volume":"63","author":"Kalil","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B2","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1056\/NEJMoa1801550","article-title":"Changes in prevalence of health care-associated infections in U.S. hospitals","volume":"379","author":"Magill","year":"2018","journal-title":"N Engl J Med"},{"key":"2024092200004852700_ciad576-B3","doi-asserted-by":"crossref","first-page":"e602","DOI":"10.1093\/cid\/ciaa1712","article-title":"Trends in hospital-acquired and ventilator-associated bacterial pneumonia trials","volume":"73","author":"Bart","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/ice.2019.296","article-title":"Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: summary of data reported to the National Healthcare Safety Network, 2015\u20132017","volume":"41","author":"Weiner-Lastinger","year":"2020","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2024092200004852700_ciad576-B5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41579-019-0293-3","article-title":"Antibiotic development\u2014economic, regulatory and societal challenges","volume":"18","author":"\u00c5rdal","year":"2020","journal-title":"Nat Rev Microbiol"},{"issue":"Suppl 2","key":"2024092200004852700_ciad576-B6","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1093\/cid\/ciw258","article-title":"Improving conduct and feasibility of clinical trials to evaluate antibacterial drugs to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia: recommendations of the Clinical Trials Transformation Initiative Antibacterial Drug Development Project Team","volume":"63","author":"Knirsch","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B7","doi-asserted-by":"crossref","first-page":"e420","DOI":"10.1093\/cid\/ciaa092","article-title":"Antibiotic development incentives that reflect societal value of antibiotics","volume":"72","author":"Boucher","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B8","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1086\/653033","article-title":"Challenges in the design and conduct of clinical trials for hospital-acquired pneumonia and ventilator-associated pneumonia: an industry perspective","volume":"51","author":"Barriere","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B9","author":"US Department of Health and Human Services","year":"2020"},{"key":"2024092200004852700_ciad576-B10","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1093\/infdis\/jiy578","article-title":"Evidence-based study design for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia","volume":"219","author":"Talbot","year":"2019","journal-title":"J Infect Dis"},{"key":"2024092200004852700_ciad576-B11","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1093\/cid\/civ927","article-title":"Developing outcomes assessments as endpoints for registrational clinical trials of antibacterial drugs: 2015 update from the Biomarkers Consortium of the Foundation for the National Institutes of Health","volume":"62","author":"Talbot","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B12","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1093\/cid\/civ495","article-title":"Desirability of outcome ranking (DOOR) and response adjusted for duration of antibiotic risk (RADAR)","volume":"61","author":"Evans","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B13","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1080\/19466315.2016.1207561","article-title":"Using outcomes to analyze patients rather than patients to analyze outcomes: a step toward pragmatism in benefit:risk evaluation","volume":"8","author":"Evans","year":"2016","journal-title":"Stat Biopharm Res"},{"key":"2024092200004852700_ciad576-B14","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1093\/cid\/ciy766","article-title":"Good studies evaluate the disease while great studies evaluate the patient: development and application of a desirability of outcome ranking endpoint for Staphylococcus aureus bloodstream infection","volume":"68","author":"Doernberg","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B15","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S1473-3099(19)30755-8","article-title":"Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study","volume":"20","author":"van Duin","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2024092200004852700_ciad576-B16","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/cid\/ciw243","article-title":"Ceftazidime\/avibactam and ceftolozane\/tazobactam: second-generation \u03b2-lactam\/\u03b2-lactamase inhibitor combinations","volume":"63","author":"van Duin","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B17","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1093\/cid\/ciz460","article-title":"The emperor's new clothes: prospective observational evaluation of the association between initial vancomycin exposure and failure rates among adult hospitalized patients with methicillin-resistant Staphylococcus aureus bloodstream infections (PROVIDE)","volume":"70","author":"Lodise","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B18","doi-asserted-by":"crossref","first-page":"e1157","DOI":"10.1093\/cid\/ciac692","article-title":"Improving traditional registrational trial end points: development and application of a desirability of outcome ranking end point for complicated urinary tract infection clinical trials","volume":"76","author":"Howard-Anderson","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B19","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/cid\/ciad239","article-title":"Exploration of a potential desirability of outcome ranking endpoint for complicated intra-abdominal infections using 9 registrational trials for antibacterial drugs","volume":"77","author":"Kinamon","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B20","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/cid\/cir895","article-title":"Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study","volume":"54","author":"Wunderink","year":"2012","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B21","doi-asserted-by":"crossref","first-page":"e710","DOI":"10.1093\/cid\/ciab032","article-title":"A phase 3, randomized, double-blind study comparing tedizolid phosphate and linezolid for treatment of ventilated gram-positive hospital-acquired or ventilator-associated bacterial pneumonia","volume":"73","author":"Wunderink","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2024092200004852700_ciad576-B22","author":"US Food and Drug Administration","year":"2018"},{"key":"2024092200004852700_ciad576-B23","doi-asserted-by":"crossref","first-page":"509","DOI":"10.2307\/2531493","article-title":"Distribution-free confidence intervals for a parameter of Wilcoxon-Mann-Whitney type for ordered categories and progressive censoring","volume":"45","author":"Halperin","year":"1989","journal-title":"Biometrics"},{"key":"2024092200004852700_ciad576-B24","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00605-19","article-title":"Reappraisal of linezolid dosing in renal impairment to improve safety","volume":"63","author":"Crass","year":"2019","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciad576\/52010101\/ciad576.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/78\/2\/259\/56697840\/ciad576.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/78\/2\/259\/56697840\/ciad576.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,22]],"date-time":"2024-09-22T00:00:58Z","timestamp":1726963258000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/78\/2\/259\/7280930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,22]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,9,22]]},"published-print":{"date-parts":[[2024,2,17]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciad576","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,2,15]]},"published":{"date-parts":[[2023,9,22]]}}}