Browsing by Author "Nambiar, Sumathi"
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Item Open Access Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials.(Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023-02) Howard-Anderson, Jessica; Hamasaki, Toshimitsu; Dai, Weixiao; Collyar, Deborah; Rubin, Daniel; Nambiar, Sumathi; Kinamon, Tori; Hill, Carol; Gelone, Steven P; Mariano, David; Baba, Takamichi; Holland, Thomas L; Doernberg, Sarah B; Chambers, Henry F; Fowler, Vance G; Evans, Scott R; Boucher, Helen WBackground
Traditional 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.Methods
Through 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.Results
In 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.Conclusions
DOOR 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.Item Open Access Pediatric Antibacterial and Antifungal Trials From 2007 to 2017.(Pediatrics, 2018-09) Thaden, Joshua T; Chiswell, Karen; Jaffe, Ian; Bergin, Stephen P; Yang, William E; Romaine, Andrew; Roberts, Jamie; Nambiar, Sumathi; Farley, John; Benjamin, Daniel K; Smith, P Brian; Tsalik, Ephraim LBACKGROUND AND OBJECTIVES:The impact of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) on pediatric antibacterial or antifungal drug trials is unknown. Our objective was to identify and characterize trials conducted under the BPCA and/or the PREA. METHODS:Pediatric antibacterial and antifungal drug trials with industry or US federal funding registered in clinicaltrials.gov from 2007 to 2017 were identified. Those conducted under BPCA and/or PREA were identified through US Food and Drug Administration and National Institute of Child Health and Human Development databases. RESULTS:Of 17 495 pediatric trials registered on clinicaltrials.gov between October 2007 and September 2017, 122 systemic antibacterial or antifungal drug trials with industry or US federal funding were identified. Of these 122 trials, 98 (80%) involved antibacterials only, 23 (19%) antifungals only, and 1 (1%) both antibacterials and antifungals. These represented <1% (122 of 17 495) of pediatric trials. Neither pediatric antibacterial nor antifungal drug trials commonly enrolled neonates 0 to 30 days old (30% [30 of 99] vs 42% [10 of 24], respectively). Pediatric antibacterial and antifungal trials were commonly industry funded (79% [78 of 99] and 83% [20 of 24], respectively). In total, 65% (79 of 122) of pediatric antibacterial and/or antifungal drug trials were conducted under BPCA and/or PREA. Researchers in trials conducted under BPCA and/or PREA, relative to non-BPCA and/or PREA trials, more often collected pharmacokinetic data (70% [55 of 79] vs 26% [11 of 43]). CONCLUSIONS:Although the majority of pediatric antibacterial and/or antifungal drug trials were conducted under BPCA and/or PREA, the overall number was low. Greater effort is needed to stimulate such trials.