A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients

Transplant ID Diagnostics Consensus Conference Working Group

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1 Scopus citations

Abstract

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.

Original languageEnglish (US)
Pages (from-to)3150-3169
Number of pages20
JournalAmerican Journal of Transplantation
Volume22
Issue number12
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
High‐quality diagnostics facilitate early detection and treatment of infections and are central to the optimal management of SOTR. To gain endorsement from regulatory agencies for clinical use, diagnostic tests must first demonstrate analytical validity in the laboratory environment (accuracy, precision, and reproducibility in detecting an intended analyte) under CMS/CLIA oversight, followed by clinical validity (correlation with presence, absence of or risk for a specific disease), and utility (positive impact on clinical decision making) for the intended‐use population per FDA mandate. A proposed ideal pathway for the development of ID diagnostics was outlined (Figure 1 ). In addition, several barriers to the assessment of clinical validity and thus regulatory approval of emerging infectious disease diagnostics, particularly in transplantation were identified. These include (1) lack of analytical validity data in the intended‐use transplant population, (2) lack of established reference standard tests for use as comparators, and (3) inadequate funding for multicenter prospective randomized studies. To overcome these barriers, an FDA advisory panel composed of transplant infectious disease and microbiology experts should partner with FDA to determine acceptable composite reference standards (combining multiple tests and/or clinical criteria) when a single predicate test is unavailable as well as a framework to standardize validation. Additionally, collaboration between industry and FDA is needed to establish optimal study design and identify the least burdensome pathway toward approval. To support a diverse array of transplant infectious disease diagnostics (as well as therapeutics) research involving investigators across multiple transplant centers, funding should be sought from NIH through submission of research program project grants and from industry with the endorsement of AST, IDSA, the American Society for Microbiology, transplant patient advocacy groups and other stakeholders. Establishing the clinical utility of much‐needed diagnostics should pave the way for improved CMS reimbursement schemes to adequately cover testing costs. 59

Funding Information:
The authors express their appreciation and gratitude to Dr. Laurine Bow, Anne Kreiss, Amber Nolan, and Melissa Patterson for their assistance in organizing this conference and for Dr. Ribhi Shawar for providing conference attendees with an overview of regulatory approval of infectious disease diagnostics from the FDA perspective.

Publisher Copyright:
© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.

Keywords

  • clinical research/practice
  • diagnostic techniques and imaging
  • infection and infectious agents
  • infectious disease
  • organ transplantation in general
  • translational research/science

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