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Exploration of a Potential Desirability of Outcome Ranking Endpoint for Complicated Intra-Abdominal Infections Using 9 Registrational Trials for Antibacterial Drugs

Journal Article · · Clinical Infectious Diseases
DOI:https://doi.org/10.1093/cid/ciad239· OSTI ID:2425674
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Abstract Background

Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI).

Methods

Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and, for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator.

Results

Three key findings informed the cIAI-specific DOOR endpoint: (1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; (2) infectious complications of cIAI were diverse; and (3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment versus comparator.

Conclusions

We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease–specific DOOR endpoints.

Research Organization:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
DOE Contract Number:
SC0014664
OSTI ID:
2425674
Journal Information:
Clinical Infectious Diseases, Journal Name: Clinical Infectious Diseases Journal Issue: 4 Vol. 77; ISSN 1058-4838
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English

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