1066. BAC DOOR: A Clinician Ranking Exercise for Better S. aureus Bacteremia Trial Design
Session: Poster Abstract Session: Clinical Infectious Diseases: Bacteremia and Endocarditis
Friday, October 28, 2016
Room: Poster Hall
Posters
  • ID Week 2016 BAC DOOR poster.pdf (644.1 kB)
  • Background: New therapies are needed for S. aureus bacteremia (SAB). However, when comparing new antibiotic regimens, the oft-used noninferiority design fails to address the fundamental question of which treatment is better for patients. Desirability of Outcome Ranking (DOOR) is a novel method for analysis of clinical trials. Patients are ranked according to overall outcomes, taking into account both benefits and harms. We conducted a study to develop a novel DOOR strategy to utilize in future SAB treatment trials.

    Methods: Twenty SAB patient profiles were constructed by a team of ID physicians to represent the range of experiences and outcomes observed in prior trials. The profiles described the efficacy, adverse events (AEs), and treatment adjustments of a patient during a theoretical trial comparing two treatments. A computerized survey with profiles presented in random order was sent to 43 ID clinicians working in the USA (28% pediatric). The respondents were asked to rank the 20 profiles from best to worst on the basis of global outcome. We measured the agreement between respondent ranks and several pre-specified DOOR algorithms developed by the research team. Additionally, a DOOR strategy based on the respondent consensus was developed using classification and regression tree (CART) and other analyses.

    Results: Forty-two (97%) respondents completed the survey. Respondent rankings demonstrated good agreement (median Spearman correlation r=0.69, IQR 0.60-0.77). Patients with extreme positive or negative outcomes proved easy to discriminate. However, groups of patients in the middle had similar rankings (Figure 1). CART analyses suggested that features best discriminating rank are survival, severe AE, cure, infectious complications, and ongoing symptoms. Based on these analyses, we developed a DOOR strategy (Figure 2), which correlates well with the respondent consensus ranking (r=0.89).

    Conclusion: When comparing SAB patient profiles, respondents place value not just on cure, but also on AEs and symptom resolution. A DOOR strategy incorporating these outcomes can be used for future trials comparing treatment strategies for SAB and other infections with the goal of improved differentiation between management strategies.

    Figure  SEQ Figure \* ARABIC 1: Clinician Rankings by Patient

    Sarah Doernberg, MD1, Natalia Gouskova, PhD2, Scott Evans, PhD, MS3, Helen Boucher, MD, FIDSA4, G Corey, MD5, Sara Cosgrove, MD, MS, FIDSA, FSHEA6, Henry Chambers, MD, FIDSA1, Vance Fowler, MD7 and Thomas Holland, MD, MSc-GH8, (1)University of California, San Francisco, San Francisco, CA, (2)Harvard University, Chapel Hill, NC, (3)Department of Biostatistics and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA, (4)Tufts University, Boston, MA, (5)Duke Univ. Med. Ctr., Durham, NC, (6)Department of Medicine, Division of Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, MD, (7)Duke University, Durham, NC, (8)Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC

    Disclosures:

    S. Doernberg, None

    N. Gouskova, None

    S. Evans, None

    H. Boucher, None

    G. Corey, None

    S. Cosgrove, None

    H. Chambers, None

    V. Fowler, Pfizer: Consultant and Grant Investigator , Consulting fee and Research grant
    Novartis: Consultant , Consulting fee
    Galderma: Consultant , Consulting fee
    Novadigm: Consultant , Consulting fee
    Durata: Consultant , Consulting fee
    Debiopharm: Consultant , Consulting fee
    Genentech: Consultant , Consulting fee
    Achaogen: Consultant , Consulting fee
    Affinium: Consultant , Consulting fee
    Medicines Co: Consultant , Consulting fee
    Cerexa: Consultant and Grant Investigator , Consulting fee and Grant recipient
    Tetraphase: Consultant , Consulting fee
    Trius: Consultant , Consulting fee
    MedImmune: Consultant and Grant Investigator , Consulting fee and Grant recipient
    Bayer: Consultant , Consulting fee
    Theravance: Grant Investigator and Scientific Advisor , Research grant
    Cubist/Merck: Consultant and Grant Investigator , Consulting fee and Research grant
    Basilea: Consultant , Consulting fee
    Affinergy: Consultant and Grant Investigator , Consulting fee and Research support
    Janssen: Consultant , Consulting fee
    Actavis/Forest/Cerexa: Grant Investigator , Grant recipient
    Advanced Liquid Logics: Grant Investigator , Research support
    Novartis: Consultant , Consulting fee
    Medical Biosurfaces: Grant Investigator , Research support
    Locus: Grant Investigator , Research support
    Contrafect: Grant Investigator , Grant recipient
    Karius: Grant Investigator , Grant recipient
    Green Cross: Consultant , Speaker honorarium

    T. Holland, Basilea Pharmaceutica: Consultant , Consulting fee
    The Medicines Company: Consultant , Consulting fee

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.