title: Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR).
abstract: Clinical trials that compare strategies to optimize antibiotic use are of critical importance but are limited by competing risks that distort outcome interpretation, complexities of noninferiority trials, large sample sizes, and inadequate evaluation of benefits and harms at the patient level. The Antibacterial Resistance Leadership Group strives to overcome these challenges through innovative trial design. Response adjusted for duration of antibiotic risk (RADAR) is a novel methodology utilizing a superiority design and a 2-step process: (1) categorizing patients into an overall clinical outcome (based on benefits and harms), and (2) ranking patients with respect to a desirability of outcome ranking (DOOR). DOORs are constructed by assigning higher ranks to patients with (1) better overall clinical outcomes and (2) shorter durations of antibiotic use for similar overall clinical outcomes. DOOR distributions are compared between antibiotic use strategies. The probability that a randomly selected patient will have a better DOOR if assigned to the new strategy is estimated. DOOR/RADAR represents a new paradigm in assessing the risks and benefits of new strategies to optimize antibiotic use.
authors.affiliation: Harvard University, Boston, Massachusetts.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Evans
authors.affiliation: Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rubin
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
authors.forename: Dean
authors.initials: D
authors.lastname: Follmann
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gene
authors.initials: G
authors.lastname: Pennello
authors.affiliation: Division of Pediatric Infectious Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: W Charles
authors.initials: WC
authors.lastname: Huskins
authors.affiliation: George Washington University School of Medicine, Washington D.C. Leidos Biomedical Research in support of the Division of Clinical Research, National Institutes of Health, Bethesda, Maryland.
authors.forename: John H
authors.initials: JH
authors.lastname: Powers
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: David
authors.initials: D
authors.lastname: Schoenfeld
authors.affiliation: Pfizer, Inc, Groton, Connecticut.
authors.forename: Christy
authors.initials: C
authors.lastname: Chuang-Stein
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Cosgrove
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.affiliation: University of Pennsylvania, Philadelphia.
authors.forename: Ebbing
authors.initials: E
authors.lastname: Lautenbach
authors.affiliation: University of California, San Francisco.
authors.forename: Henry F
authors.initials: HF
authors.lastname: Chambers
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy; D002986:Clinical Trials as Topic; D024881:Drug Resistance, Bacterial; D006801:Humans; D061214:Patient Safety; D012107:Research Design; D012306:Risk; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents
keywords: DOOR; RADAR; antibiotic use strategies