Sarah B Doernberg1, Thuy Tien Tram Tran2, Steven Y C Tong3,4, Mical Paul5,6, Dafna Yahav7,8, Joshua S Davis4,9, Leonard Leibovici8,10, Helen W Boucher11, G Ralph Corey12, Sara E Cosgrove13, Henry F Chambers1, Vance G Fowler12, Scott R Evans2, Thomas L Holland12. 1. Department of Internal Medicine, Division of Infectious Diseases, University of California, San Francisco. 2. Biostatistics Center, Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University, D.C. 3. Victorian Infectious Disease Service, the Royal Melbourne Hospital, and the University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia. 4. Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Northern Territory, Australia. 5. Institute of Infectious Diseases, Rambam Health Care Campus. 6. Faculty of Medicine, Technion, Israel Institute of Technology, Haifa. 7. Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, Petah Tikva. 8. Sackler Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Israel. 9. Department of Infectious Diseases, John Hunter Hospital, Newcastle, New South Wales, Australia. 10. Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. 11. Tufts Medical Center, Infectious Diseases, Boston, Massachusetts. 12. Duke University Medical Center, Durham, North Carolina. 13. Department of Antimicrobial Stewardship, Johns Hopkins University, Baltimore, Maryland.
Abstract
BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data. METHODS: We administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100% to the most desirable outcome, 0% to the least, and "partial credit" to intermediate ranks. RESULTS: Forty-two recipients (97%) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95% confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis. CONCLUSIONS: Using S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.
BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data. METHODS: We administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100% to the most desirable outcome, 0% to the least, and "partial credit" to intermediate ranks. RESULTS: Forty-two recipients (97%) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95% confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis. CONCLUSIONS: Using S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.
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