Sarah B. Doernberg, MD, MAS
Associate Professor
Medical Director of Adult Antibiotic Stewardship
University of California, San Francisco

I consider my role in ARLG as a “Trialist in Training.” I have been involved in the development and execution of protocols for three studies:

1) MASTER GC: Performance of Nucleic Acid Amplification Tests for the Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in extragenital sites. This novel study involved collaboration with three manufacturers and input from the Food and Drug Administration (FDA) to evaluate performance of molecular diagnostic tests for extragenital gonorrhea and chlamydia. The primary goal was for the study results to support each company’s FDA application. This trial used the MASTERMIND (MASTER protocol for evaluating Multiple INfection Diagnostics) concept developed by the ARLG that is based on the following premise: One single participant can provide information and samples for the simultaneous evaluation of multiple diagnostics. The MASTER GC trial has completed enrollment of more than 2700 participants at nine sites. FDA submissions from the participating manufacturers and manuscripts from the scientists are underway.

2) RAPIDS GN: RAPid IDentification and phenotypic Susceptibility testing for Gram-Negative bacteremia. This randomized controlled trial is studying the impact of a platform that rapidly identifies and performs antimicrobial susceptibility testing on antimicrobial utilization and clinical outcomes in patients with Gram-negative bacillus bacteremia. The trial has just completed enrollment of 500 participants at two sites.

3) The third protocol consists of multiple, separate studies to improve Staphylococcus aureus bloodstream infection (BSI) trial design. These studies incorporate mixed methods to define a novel Desirability of Outcome Ranking (DOOR) endpoint as well as to develop a quality of life (QoL) measure for patients with S. aureus BSI. The DOOR endpoint was developed through a survey to infectious diseases clinicians. It has been used for the secondary analysis of two completed trials and disseminated widely at several international conferences. The S. aureus DOOR endpoint is now published in Clinical Infectious Diseases. We will continue to collaborate with other researchers on use of this innovative approach and anticipate using it in future ARLG trials. Manuscript development is underway from the first phase of the QoL substudy of patients with bloodstream infection, which will lay the groundwork for future studies and a validated measure of QoL for BSI.

Impact of these ARLG studies

Each study I have been involved with carries important contributions to the fight against antimicrobial resistance. The MASTER-GC study is novel in its ability to generate diagnostic performance data from a single sample that collaborating manufacturers can use to support their own FDA submissions. This design approach brings efficiencies and economies of scale that can be adapted for other infectious diseases studies of novel diagnostics.

The RAPIDS GN study takes a pragmatic approach to evaluate the impact of a novel diagnostic on clinical outcomes. Lessons learned from this study will be critical to inform future approaches to the implementation of the many diagnostics that are coming into the market. The studies for S. aureus BSI will contribute to a shift in how clinical trials for this condition are designed and analyzed resulting in more data to inform clinicians facing complex treatment decisions. All of these studies will advance our knowledge in the ability to detect and manage complex antimicrobial-resistant infections.

Impact of ARLG research funding to my career

Being a Trialist in Training and protocol clinician on several high-impact studies has been a transformative training experience, providing practical skills so I can progressively manage and lead future studies to advance ARLG’s mission. The mentorship and opportunities provided to me have been unparalleled and it is difficult to imagine how I would have gained the skills and knowledge in clinical trials without the ARLG. I am extremely grateful for the support that I have received.

Benefits of ARLG

The entire ARLG organization, from the operations team to the committee members and investigators, thrives on an innovative dedication to the vital challenge of addressing antibiotic resistance. The work being done by ARLG will influence and improve this problem for the generations to come.