Table 2.
Antibacterial Resistance Leadership Group Innovation in Clinical Trials Design
| Clinical trial design | ||
|---|---|---|
| Program | Purpose | Status |
| DOOR | Uses partial credit strategies involving an ordinal ranking of global outcome to analyze patients | Published. Used in interventional trials [18] and cohort studies [2, 8]. |
| National Institutes of Health–FDA collaboration | Creates standardized, validated, publicly available DOOR and QOL end points for common entry indications in infectious diseases to be available for use by industry as exploratory end points within registrational clinical trials of novel antibiotics for FDA approval | Bloodstream infection: published, validated, and integrated QOL [17, 21] and DOOR [23] measures into clinical trial (DOTS). Acute bacterial skin and skin structure infection, complicated urinary tract infection, hospital-acquired/ventilator-associated bacterial pneumonia ,intraabdominal infection; in progress. |
| Diagnostics trial design | ||
| Program | Purpose | Status |
| MASTERMIND (MASTER protocol for Evaluating Multiple INfection Diagnostics) | Allows evaluation and comparison of multiple diagnostic tests on biological samples from a single patient | MASTERMIND-GC: Published [11]. Study of >2500 patients simultaneously led to FDA approval of 2 diagnostic platforms. MASTERMIND-BSI: in development. |
| SMART COMPASS (Sequential, Multiple-Assignment, Randomized Trials for COMparing Personalized Antibiotic StrategieS) | Allows for pragmatic assessment of patient-management strategies that span empiric and definitive therapy choices | Published [24]. |
| BED-FRAME (Benefit-Risk Evaluation of Diagnostics: A Framework) | Introduces the diagnostic yield concept and incorporates prevalence and the relative importance of diagnostic errors | Published [25]. Used to evaluate rapid molecular diagnostics in carbapenem-resistant Enterobacterales [26], Pseudomonas aeruginosa [27], and Acinetobacter baumannii [28]. |
| AWA (Average Weighted Accuracy) | Extends BED-FRAME to allow pragmatic assessment of diagnostic utility | Published [29]. |
| DOOR MAT (DOOR for the Management of Antimicrobial Therapy) | Quantitatively evaluates the desirability of antibiotic selection to evaluate utility of stewardship strategies | Published [30] |
| Isolate Biorepository | Web-based catalogue that offers the research community access to clinically, genotypically, and phenotypically well-characterized multidrug-resistant bacteria for research and development | Active: >2300 isolates provided to research community to date [19]. |
Abbreviations: DOOR, desirability of outcome ranking; FDA, US Food and Drug Administration; MASTERMIND BSI, MASTER protocol for evaluating Multiple INfection Diagnostics for rapid detection of BloodStream Infection; QOL, quality of life.