Evidence map›Paper›PMID 36031403›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023

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

Jessica Howard-Anderson, Toshimitsu Hamasaki, Weixiao Dai, Deborah Collyar, Daniel Rubin, Sumathi Nambiar, Tori Kinamon, Carol Hill, Steven P Gelone, David Mariano and 7 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
8.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 34 citations in OpenAlex.

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  8. Making Sense of Hierarchical Composite End Points in Randomized Clinical Trials-A Primer for Infectious Diseases Clinicians and Researchers.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
    Review
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  11. Interagency Collaboration for Patient-Centered Antibacterial Drug Development.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 9 institutions in 2 countries.

Jessica Howard-AndersonDepartment of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.ORCID 0000-0001-9924-0458
Toshimitsu HamasakiBiostatistics Center and Department of Biostatics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
Weixiao DaiBiostatistics Center and Department of Biostatics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
Deborah CollyarPatient Advocates in Research, Danville, California, USA.
Daniel RubinCenter for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Sumathi NambiarJohnson & Johnson, Raritan, New Jersey, USA.
Tori KinamonCenter for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Carol HillDuke Clinical Research Institute, Durham, North Carolina, USA.
Steven P GeloneNabriva Therapeutics US, Inc, Fort Washington, Pennsylvania, USA.
David MarianoNabriva Therapeutics US, Inc, Fort Washington, Pennsylvania, USA.
Takamichi BabaBiostatistics Center, Shionogi & Co, Ltd, Osaka, Japan.
Thomas L HollandDuke Clinical Research Institute, Durham, North Carolina, USA.
Sarah B DoernbergDepartment of Medicine, Division of Infectious Diseases, University of California, San Francisco, California, USA.
Henry F ChambersDepartment of Medicine, Division of Infectious Diseases, University of California, San Francisco, California, USA.
Vance G FowlerDuke Clinical Research Institute, Durham, North Carolina, USA.
Scott R EvansBiostatistics Center and Department of Biostatics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
Helen W BoucherTufts University School of Medicine and Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts, USA.
Clinical Research Institute · USMilken Institute · USUnited States Food and Drug Administration · USUniversity of California, San Francisco · USEmory University · USJohnson & Johnson (United States) · USOrthopaedic Research of Virginia · USShionogi (Japan) · JPTufts University · US

Funding

Antibacterial Resistance Leadership Group (ARLG)UM1AI104681 · NIAID · DUKE UNIVERSITY · PI Vance G. Fowler, Henry F HENRY CHAMBERS · 2013 to 2026
$180.8M
NIAID NIH HHS UM1 AI104681NIH HHS UM1AI104681
6 · The paper itself

Abstract

backgroundTraditional 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.

methodsThrough 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.

resultsIn 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.

conclusionsDOOR 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.

Indexed as

Anti-Bacterial AgentsUrinary Tract InfectionsDoripenemHumansImipenemLevofloxacinAnti-Bacterial AgentsDoripenemImipenemLevofloxacinclinical trialscomplicated urinary tract infectionsdesirability of outcome rankingdrug development

Identifiers

PMID36031403
PMCPMC10169394
OpenAlexW4293512124

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.