Metagenomic Sequencing Across the Infectious Disease Risk and Care Continuum

The AXIS Network is a prospective, multicenter observational registry designed to evaluate the real-world use of metagenomic sequencing across the infectious disease care continuum. The registry serves as a scalable platform for generating real-world evidence regarding how sequencing-based infectious disease diagnostics are utilized in clinical practice and how diagnostic information influences patient management and outcomes.

AXIS is structured as a master protocol with modular cohort appendices that allow evaluation of metagenomic sequencing across diverse patient populations, clinical syndromes, care settings, specimen types, and clinical use contexts. Cohorts may include participants undergoing metagenomic sequencing as part of routine clinical care, participants receiving usual-care diagnostic testing without sequencing, or both, depending on the objectives of the specific cohort.

The registry is designed to evaluate metagenomic sequencing in several clinical contexts, including:

Diagnostic evaluation of patients with suspected infection Surveillance of populations at increased risk for infection Longitudinal monitoring of treatment response or recurrent infection

AXIS places particular emphasis on immunocompromised populations, including patients with hematologic malignancies, solid organ transplant recipients, hematopoietic stem cell transplant recipients, individuals receiving immunosuppressive therapies, and other high-risk populations. Both adult and pediatric participants may be enrolled, depending on cohort-specific eligibility criteria.

No study-mandated interventions, treatments, or diagnostic procedures are performed. All diagnostic testing and clinical management decisions are made by treating clinicians according to routine clinical practice. Data are collected through a combination of standardized case report forms and structured extraction of electronic health record data.

Data collected may include:

Demographic and baseline clinical characteristics Diagnostic testing and timing of results Antimicrobial administration and management decisions Procedures and healthcare utilization Clinical outcomes, including mortality and readmissions Longitudinal follow-up information, where applicable

The primary objective of AXIS is to evaluate how metagenomic sequencing informs clinical decision-making and its association with downstream management decisions and clinical outcomes across defined cohorts.

Secondary objectives include:

Characterizing real-world utilization patterns of metagenomic sequencing Describing integration of sequencing results into diagnostic evaluation Evaluating infection-related clinical management decisions associated with sequencing results Assessing longitudinal monitoring and surveillance applications Evaluating healthcare utilization outcomes

Exploratory objectives include assessment of patient-centered outcomes, development of predictive models and clinical decision-support approaches, and establishment of an interactome biobank utilizing residual clinical specimens where permitted.

Approximately 50 sites in the United States are expected to participate. The registry is designed to enroll up to approximately 10,000 participants over a planned study duration of approximately seven years. Data generated through AXIS are intended to improve understanding of how metagenomic sequencing is used in routine clinical practice and to inform future research, clinical care strategies, and diagnostic innovation.

Inclusion criteria

• Participant receives care at a participating AXIS site.
• Participant meets eligibility criteria for at least one active AXIS cohort as defined in the applicable cohort appendix.
• Participant or legally authorized representative is able to provide informed consent, unless waived by the reviewing IRB.

Exclusion criteria

• Any condition that, in the opinion of the investigator, would make participation inappropriate or prevent completion of required study procedures.
• Additional cohort-specific exclusion criteria may apply and are defined within the applicable cohort appendix.