Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Acute Bacterial Skin and Skin Structure Infections.

BACKGROUND: Desirability of outcome ranking (DOOR), a paradigm for the design, analysis, and interpretation of clinical trials based on patient-centered benefit-risk evaluation, could help inform drug development for acute bacterial skin and skin structure infections (ABSSSIs). METHOD: A multidisciplinary committee created an infectious diseases DOOR endpoint, incorporating clinical response, infectious complications, serious adverse events, and mortality, and adapted this for ABSSSI. We retrospectively applied DOOR to 2 previous ABSSSI randomized controlled registrational trials (OASIS-1 and OASIS-2), both comparing omadacycline with linezolid. We evaluated the DOOR distribution and estimated the probability of having a more desirable outcome with omadacycline compared with linezolid. For OASIS-2, we used the 36-Item Short Form Health Survey Version 2 (SF-36v2) scores as a "tiebreaker" for participants who would otherwise have the same DOOR outcome. We performed DOOR component, partial credit, and subgroup analyses. RESULTS: The ABSSSI DOOR demonstrated similar overall clinical outcomes between treatment arms for OASIS-1 and OASIS-2. The probability of a more desirable outcome for a participant treated with omadacycline, compared with linezolid, was 50.6% (95% confidence interval [CI], 47.4%-53.7%) and 52.1% (95% CI, 49.2%-55.0%) in OASIS-1 and OASIS-2, respectively. In OASIS-2, applying a health-related quality-of-life score as a tiebreaker did not significantly change the DOOR probability. Partial credit and subgroup analyses demonstrated similar overall results. CONCLUSIONS: DOOR may provide additional perspective on benefit versus risk in individual patients in ABSSSI trials. Future trials using DOOR prospectively will continue inform how to incorporate patient-centered outcomes in ABSSSI trials.

Duke Scholars

Author Thomas Lawrence Holland Medicine, Infectious Diseases

Author Vance Garrison Fowler Jr. Medicine, Infectious Diseases

Author Heather Alyse King Population Health Sciences