Improving Traditional Registrational Trial Endpoints: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Complicated Urinary Tract Infection Clinical Trials
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
clinical trials; complicated urinary tract infections; desirability of outcome ranking; drug development
BACKGROUND: Traditional endpoints used in registrational randomized controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience. METHODS: Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience we developed a DOOR endpoint for infectious disease syndromes and demonstrated how this could be applied to three registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTI). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI cefiderocol to imipenem and DORI-05 doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug. RESULTS: In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR. CONCLUSIONS: DOOR can effectively be utilized in registrational cUTI trials. The DOOR endpoint presented here can be adapted for other infectious diseases syndromes and prospectively incorporated into future clinical trials.
Howard-Anderson, Jessica; Hamasaki, Toshimitsu; Dai, Weixiao; Collyar, Deborah; Rubin, Daniel; Nambiar, Sumathi; Kinamon, Tori; Hill, Carol; Gelone, Steven P.; Mariano, David; Baba, Takamichi; Holland, Thomas L.; Doernberg, Sarah B.; Chambers, Henry F.; Fowler, Vance G.; Evans, Scott R.; and Boucher, Helen W., "Improving Traditional Registrational Trial Endpoints: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Complicated Urinary Tract Infection Clinical Trials" (2022). GW Authored Works. Paper 1424.
Biostatistics and Bioinformatics