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

Area of Science:

• Clinical Trials
• Infectious Diseases
• Pharmacoeconomics

Background:

• Desirability of Outcome Ranking (DOOR) is a patient-centered framework for clinical trial design and analysis.
• DOOR evaluates benefit-risk profiles to inform drug development, particularly for acute bacterial skin and skin structure infections (ABSSSIs).

Purpose of the Study:

• To adapt and apply the infectious diseases DOOR endpoint to retrospectively analyze two ABSSSI registrational trials (OASIS-1 and OASIS-2).
• To compare the efficacy of omadacycline versus linezolid using the DOOR methodology and assess patient-centered outcomes.

Main Methods:

• A multidisciplinary committee developed an ABSSSI-specific DOOR endpoint including clinical response, complications, adverse events, and mortality.
• DOOR was applied retrospectively to OASIS-1 and OASIS-2 trials comparing omadacycline and linezolid.
• Health-related quality of life (SF-36v2) was used as a tiebreaker in OASIS-2; component, partial credit, and subgroup analyses were performed.

Main Results:

• The ABSSSI DOOR analysis revealed similar overall clinical outcomes between omadacycline and linezolid arms in both trials.
• The probability of a more desirable outcome with omadacycline was 50.6% (OASIS-1) and 52.1% (OASIS-2), indicating comparable or slightly favorable results.
• Using quality-of-life scores as a tiebreaker did not significantly alter the DOOR probability; subgroup analyses confirmed overall findings.

Conclusions:

• The DOOR methodology provides valuable patient-centered insights into benefit-risk assessments for ABSSSI treatments.
• Prospective implementation of DOOR in future ABSSSI trials can further refine the incorporation of patient-reported outcomes.