AUTHOR=Fallon Brian A. , Kuvaldina Mara , Zubcevik Nevena , DeBiasi Roberta , Mulkey Sarah B. , Chiu Charles , Chow Felicia , Paolino Kristopher , Lai Randy , Putrino David , Proal Amy , Pavlicova Martina , Aucott John 

TITLE=Proposed research classification criteria for Lyme disease in infection associated chronic illness studies

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1519163

DOI=10.3389/fmed.2025.1519163

ISSN=2296-858X

ABSTRACT=BackgroundResearch on patients with persistent symptoms despite prior treatment for Lyme disease can be challenging to interpret given the diversity of criteria selected to characterize Lyme disease and to define the syndrome of those with persistent symptoms. Because most research studies only include patients with well-documented prior Lyme disease, the generalizability of the study results is limited, excluding the larger group of patients often seen in community practice who do not meet these stringent enrollment criteria. Researchers at the Lyme and other Tick-borne Diseases Clinical Trials Network (LTD-CTN) recognized early on that a research classification system was needed to facilitate the design of studies that are more inclusive. This paper presents a proposed research classification system.MethodsCriteria used in published clinical research on previously treated Lyme disease were reviewed. Clinical expertise was provided by principal investigators in the LTD-CTN. Further input was obtained from a diverse panel of stakeholders in the field, including clinicians, academic researchers, and patient advocates. This classification system was developed based on feedback collected from all these sources.ResultsThe new research classification system proposes criteria for Lyme disease at different levels of diagnostic certainty: well-defined, probable, possible, and uncertain. Criteria for ascertainment for each classification level and additional factors to be considered in patient selection for research are described.ConclusionThe proposed research classification system should improve the quality and generalizability of clinical research by providing clear case definitions for enrollment of a more diverse group of patients with sequelae from Lyme disease.