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

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).

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.

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.

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.