A patient-centric paradigm and tool for clinical research: the DOOR is open

Toshimitsu Hamasaki, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Yijie He, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Qihang Wu, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
Jessica Howard-Anderson, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.
Helen W. Boucher, Tufts University School of Medicine and Tufts Medicine, Boston, Massachusetts, USA.
Sarah B. Doernberg, Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, USA.
Thomas L. Holland, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
John H. Powers, Department of Medicine, George Washington University School of Medicine, Washington, DC, USA.
Jing Wang, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Guoqing Diao, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
David van Duin, Division of Infectious Diseases, School of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA.
Vance G. Fowler, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Henry F. Chambers, Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, USA.
Scott R. Evans, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.

Document Type

Journal Article

Publication Date

11-24-2025

Journal

Antimicrobial agents and chemotherapy

DOI

10.1128/aac.01478-25

Keywords

DOOR; DOOR probability; benefit:risk; partial credit; patient-centric; pragmatic trial

Abstract

Randomized clinical trials are the gold standard for evaluating the benefits and harms of interventions and yet may not provide the evidence needed to inform medical decision-making, an ultimate goal for clinical research. Commonly used design and analysis approaches are often not suited to answer the most important questions to inform clinical practice, specifically how do resulting patient experiences, when comprehensively considering benefits and harms, compare between therapeutic alternatives? The standard approach of siloed analysis of one outcome at a time: (i) does not incorporate associations between multiple outcomes; (ii) does not recognize the cumulative nature of multiple outcomes in individual patients or recognize important gradations of global patient response; (iii) suffers from competing risk complexities during interpretation of individual outcomes; (iv) provides for ambiguous generalizability with respect to benefit:risk since efficacy and safety analyses are often conducted on different populations. Evaluation of treatment effect heterogeneity to identify subgroups for treatment or avoidance of treatment is typically evaluated based on a single efficacy or safety endpoint and rarely evaluated based on the overall benefit:risk. Methods that quantify and compare the patient experience are needed. The desirability of outcome ranking (DOOR) is a paradigm for the design, monitoring, analysis, interpretation, and reporting of clinical trials and other research studies based on patient-centric benefit:risk evaluation, developed to address these issues and advance clinical trial science. Aligning the clinical research strategy with the relevant question for clinical practice will enhance research applicability. Careful design and comprehensive analyses are critical for DOOR paradigm application. We provide a recommended statistical analysis plan for research studies implementing DOOR, describe its elements, and illustrate analysis application using examples. A freely available online tool for the recommended analyses and the design of studies implementing the DOOR paradigm is provided.ClinicalTrials.gov ID: NCT05641298.

Department

Biostatistics and Bioinformatics

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