Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR)

Scott R Evans; Daniel Rubin; Dean Follmann; Gene Pennello; W Charles Huskins; John H Powers; David Schoenfeld; Christy Chuang-Stein; Sara E Cosgrove; Vance G Fowler Jr; Ebbing Lautenbach; Henry F Chambers

doi:10.1093/cid/civ495

Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR)

Clin Infect Dis. 2015 Sep 1;61(5):800-6. doi: 10.1093/cid/civ495. Epub 2015 Jun 25.

Authors

Affiliations

¹ Harvard University, Boston, Massachusetts.
² Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring.
³ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
⁴ Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
⁵ Division of Pediatric Infectious Diseases, Mayo Clinic, Rochester, Minnesota.
⁶ 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.
⁷ Massachusetts General Hospital, Boston.
⁸ Pfizer, Inc, Groton, Connecticut.
⁹ Johns Hopkins University, Baltimore, Maryland.
¹⁰ Duke University, Durham, North Carolina.
¹¹ University of Pennsylvania, Philadelphia.
¹² University of California, San Francisco.

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.

Keywords: DOOR; RADAR; antibiotic use strategies.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Anti-Bacterial Agents / administration & dosage*
Anti-Bacterial Agents / therapeutic use*
Bacterial Infections / drug therapy
Clinical Trials as Topic*
Drug Resistance, Bacterial*
Humans
Patient Safety
Research Design*
Risk
Treatment Outcome

Substances

Anti-Bacterial Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding