@article{3164c2bb4fe24f7f8fb09bc7306f1c73,
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",
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.",
keywords = "Bloodstream infection, Clinical trial, Staphylococcus aureus",
author = "{Antibacterial Resistance Leadership Group} and Doernberg, {Sarah B.} and Tran, {Thuy Tien Tram} and Tong, {Steven Y.C.} and Mical Paul and Dafna Yahav and Davis, {Joshua S.} and Leonard Leibovici and Boucher, {Helen W.} and {Ralph Corey}, G. and Cosgrove, {Sara E.} and Chambers, {Henry F.} and Fowler, {Vance G.} and Evans, {Scott R.} and Holland, {Thomas L.}",
note = "Funding Information: Financial support. This study was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH; award UM1AI104681). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. V. G. F. was supported by the NIH (K24-AI093969). J. S. D. and S. Y. T. received salary support from Australia{\textquoteright}s National Health and Medical Research Council (Career Development Fellowships 1083105 and 1145033, respectively). Funding Information: Durata, Theravance, and Debiopharm; and royalties from UpToDate and has a patent Sepsis Diagnostics pending. T. L. H. reports grants from NIH during the conduct of the study and personal fees from Motif Bio, Basilea Pharmaceutica, Genentech, and Theravance outside the submitted work. All remaining authors: no reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Funding Information: This study was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH; award UM1AI104681). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. V. G. F. was supported by the NIH (K24-AI093969). J. S. D. and S. Y. T. received salary support from Australia's National Health and Medical Research Council (Career Development Fellowships 1083105 and 1145033, respectively). Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.",
year = "2019",
month = may,
day = "1",
doi = "10.1093/cid/ciy766",
language = "English (US)",
volume = "68",
pages = "1691--1698",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "10",
}