Scott Evans, PhD, MS
Director, Biostatistics Center
Professor and Founding Chair, Department of Biostatistics and Bioinformatics
Milken Institute School of Public Health
George Washington University

What is your specialty and primary area of focus in your therapeutic area?

Design, data monitoring, analyses, and reporting of and education in clinical trials and diagnostic studies; benefit-risk evaluation.

When did your role with the ARLG begin?

From the very beginning. I wrote the Statistical and Data Management Center (SDMC) section of the ARLG grant in 2012, and I have served as the SDMC Director since the group launched in 2013.

Please tell us more about your primary role(s) in the ARLG, projects and groups you’ve led or supported, and other contributions or work you’d like to include.

My role is multifaceted. One role is to collaborate on ARLG studies, ensuring protection of scientific research integrity throughout the study lifecycle. The SDMC gets involved at all stages of nearly every ARLG study.

Another important role is to enhance the scientific value of ARLG studies and beyond through the development and implementation of methods and tools that provide more informative answers to the most important questions. The methods may be utilized in ARLG studies, although the impact of the methods and tools are much broader. Some of the methods and tools that we have developed are DOOR, BED-FRAME / AWA, SMART COMPASS, MASTERMIND, Intention-to-Diagnose, DOOR MAT, and Predicted Interval plots (PIPs).

Lastly, it is important for us to serve as a resource for the scientific community on the design and analyses of clinical trials and diagnostic studies, particularly on complex issues in infectious diseases and antimicrobial resistance.

In your role with the ARLG, who have you mentored and how were you able to support or guide their career in AMR?

As a biostatistician, my role in mentoring clinical investigators is less structured. Perhaps I have had some indirect impact on the development of early career investigators in the ARLG through our collaborative interactions, helping them with study design, writing papers, or understanding biostatistical concepts.

There is a less heralded but important success story of mentoring early career biostatisticians. At the SDMC, we have had about a dozen doctoral students work on ARLG projects over the years. As part of their academic training, they must select dissertation topics and develop methodologies. These students, mentored by me and my ARLG faculty colleagues Professors Hamasaki and Diao, selected dissertation topics motivated by the methods developed in the ARLG, such as DOOR, BED-FRAME, and SMART-COMPASS, and created extensions to these methods.

Why is the ARLG’s mission important to you?

Antimicrobial resistance affects everyone and nearly any aspect of medicine. In addition to undermining our ability to treat specific infections, antibiotic resistance threatens the safety and effectiveness of many medical and surgical procedures that rely on having potent antibiotics to prevent infections. This includes patients undergoing chemotherapy for cancer, dialysis for renal failure, orthopedic procedures, cardiac and complex surgeries, treatment of rheumatoid arthritis, and organ and bone marrow transplantation. As you go through life, you see how important it is to conduct research in this area to address ever-evolving challenges and questions, particularly in an era of decreasing industry interest in this area of medicine. This puts a lot on ARLG’s shoulders. The ARLG’s work in conducting rigorous research studies that address questions of clinical practice importance, developing methods and tools for the research community, and seeding and developing research careers is critical.

In your opinion, what are some of the ARLG’s most important or impactful achievements?

The ARLG is finding answers to the pragmatic questions of clinical practice that industry studies are unable to answer using studies that protect research integrity. As a network we have developed a culture of thinking deeply about what the most relevant questions are and designing studies that address these most important questions. Some of the important studies that come to mind:

• The CRACKLE study that compared ceftazidime/avibactam vs. colistin for infections caused by carbapenem-resistant Enterobacterales (CRE), impacting treatment guidelines;
• The PROVIDE study that impacted treatment guidelines for vancomycin dosing for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections;
• The MASTER-GC study that evaluated the performance of nucleic acid amplification tests for the detection of Neisseria gonorrhoeae and Chlamydia trachomatis in extragenital sites, resulting in FDA clearance of the first two diagnostic tests for extragenital testing for these pathogens;
• The DOTS trial that compared dalbavancin vs standard therapy for completion of treatment of complicated aureus bacteremia, which not only informed therapy-selection but stands as one of the first trials to evaluate uses outcomes to analyze what happens to patients rather than the other way around; assessing patient data to analyze study outcomes;
• The PRIMERS series of studies that evaluated the use of rapid molecular diagnostics for informing empiric therapy decisions for infections caused by carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, three critical priority pathogens as identified by the World Health Organization;
• The FAST trial that compared rapid antimicrobial susceptibility testing (AST) performed directly from positive blood culture bottles vs. standard AST methods on clinical outcomes for gram-negative bacteremia;
• The MDRO series of studies, which provided unparalleled data and epidemiological investigations of infections due to carbapenem-resistant Enterobacterales, aeruginosa, and A.  baumannii.

The yet-to-be-reported results from the PHAGE clinical trial that is evaluating phage therapy in persons with cystic fibrosis colonized with P. aeruginosa, and the MASTERMIND-RING study evaluating multiple diagnostics for ciprofloxacin-resistant N. gonorrhoeae, will also have important impact.

The ARLG’s creative methodologies have impact far beyond the ARLG studies that utilize them. Furthermore, they raise the bar in terms of addressing the most important questions for clinical practice while protecting research integrity. The DOOR paradigm became a foundation for multiregional guidance on benefit-risk assessment from the Council for International Organizations of Medical Sciences (CIOMS). The MASTERMIND design has become an extremely valuable tool. Other methods and tools such as the intention-to-diagnose (ITD) principle and BED-FRAME are critical for advancement and growth of the field from an integrity and utility perspective.

The foundation for career development and opportunities for involvement in important projects is unmatched in this area of medicine.