Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials.

Abstract

Background

Traditional end points 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 end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared 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 used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1093/cid/ciac692

Publication Info

Howard-Anderson, Jessica, Toshimitsu Hamasaki, Weixiao Dai, Deborah Collyar, Daniel Rubin, Sumathi Nambiar, Tori Kinamon, Carol Hill, et al. (2023). Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 76(3). pp. e1157–e1165. 10.1093/cid/ciac692 Retrieved from https://hdl.handle.net/10161/29592.

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Scholars@Duke

Holland

Thomas Lawrence Holland

Associate Professor of Medicine
Fowler

Vance Garrison Fowler

Florence McAlister Distinguished Professor of Medicine

Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia
Antibacterial Resistance
Pathogenesis of Bacterial Infections
Tropical medicine/International Health


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