Good studies evaluate the disease while great studies evaluate the patient

Development and Application of a Desirability of Outcome Ranking Endpoint for Staphylococcus aureus Bloodstream Infection

Antibacterial Resistance Leadership Group

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: Desirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data. 

    Methods: We administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100% to the most desirable outcome, 0% to the least, and "partial credit" to intermediate ranks. 

    Results: Forty-two recipients (97%) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95% confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis. 

    Conclusions: Using S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.

     

    Original languageEnglish
    Pages (from-to)1691-1698
    Number of pages8
    JournalClinical Infectious Diseases
    Volume68
    Issue number10
    Early online date12 Oct 2018
    DOIs
    Publication statusPublished - 15 May 2019

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    Staphylococcus aureus
    Infection
    Communicable Diseases
    Clinical Trials
    Confidence Intervals
    Survival
    Surveys and Questionnaires
    Therapeutics

    Cite this

    @article{b9f2c14bdf0b4479b3b534972376d8e4,
    title = "Good studies evaluate the disease while great studies evaluate the patient: Development and Application of a Desirability of Outcome Ranking Endpoint for Staphylococcus aureus Bloodstream Infection",
    abstract = "Background: Desirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data.  Methods: We administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100{\%} to the most desirable outcome, 0{\%} to the least, and {"}partial credit{"} to intermediate ranks.  Results: Forty-two recipients (97{\%}) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95{\%} confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis.  Conclusions: Using S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.  ",
    keywords = "Bloodstream infection, Clinical trial, Staphylococcus aureus",
    author = "Doernberg, {Sarah B.} and Tran, {Thuy Tien Tram} and Tong, {Steven Y.C.} and Mical Paul and Dafna Yahav and Davis, {Joshua S.} and Leonard Leibovici and Boucher, {Helen W.} and {Ralph Corey}, G. and Cosgrove, {Sara E.} and Chambers, {Henry F.} and Fowler, {Vance G.} and Evans, {Scott R.} and Holland, {Thomas L.} and {Antibacterial Resistance Leadership Group}",
    year = "2019",
    month = "5",
    day = "15",
    doi = "10.1093/cid/ciy766",
    language = "English",
    volume = "68",
    pages = "1691--1698",
    journal = "Clinical Infectious Diseases",
    issn = "1058-4838",
    publisher = "Oxford University Press",
    number = "10",

    }

    Good studies evaluate the disease while great studies evaluate the patient : Development and Application of a Desirability of Outcome Ranking Endpoint for Staphylococcus aureus Bloodstream Infection. / Antibacterial Resistance Leadership Group.

    In: Clinical Infectious Diseases, Vol. 68, No. 10, 15.05.2019, p. 1691-1698.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Good studies evaluate the disease while great studies evaluate the patient

    T2 - Development and Application of a Desirability of Outcome Ranking Endpoint for Staphylococcus aureus Bloodstream Infection

    AU - Doernberg, Sarah B.

    AU - Tran, Thuy Tien Tram

    AU - Tong, Steven Y.C.

    AU - Paul, Mical

    AU - Yahav, Dafna

    AU - Davis, Joshua S.

    AU - Leibovici, Leonard

    AU - Boucher, Helen W.

    AU - Ralph Corey, G.

    AU - Cosgrove, Sara E.

    AU - Chambers, Henry F.

    AU - Fowler, Vance G.

    AU - Evans, Scott R.

    AU - Holland, Thomas L.

    AU - Antibacterial Resistance Leadership Group

    PY - 2019/5/15

    Y1 - 2019/5/15

    N2 - Background: Desirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data.  Methods: We administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100% to the most desirable outcome, 0% to the least, and "partial credit" to intermediate ranks.  Results: Forty-two recipients (97%) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95% confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis.  Conclusions: Using S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.  

    AB - Background: Desirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data.  Methods: We administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100% to the most desirable outcome, 0% to the least, and "partial credit" to intermediate ranks.  Results: Forty-two recipients (97%) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95% confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis.  Conclusions: Using S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.  

    KW - Bloodstream infection

    KW - Clinical trial

    KW - Staphylococcus aureus

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    U2 - 10.1093/cid/ciy766

    DO - 10.1093/cid/ciy766

    M3 - Article

    VL - 68

    SP - 1691

    EP - 1698

    JO - Clinical Infectious Diseases

    JF - Clinical Infectious Diseases

    SN - 1058-4838

    IS - 10

    ER -