Development and feasibility testing of the taVNS adverse events questionnaire: a multistage methodological study

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulatory therapy gaining interest for its neural mechanisms and therapeutic effects. Although taVNS is considered safe, adverse event (AE) reporting remains inconsistent, lacking standardized procedures for assessment and documentation. This study aimed to develop a new instrument and conduct a preliminary evaluation of its use for systematic and structured assessment and reporting of AEs associated with taVNS. To achieve this objective, a multistage development process was undertaken, comprising: item generation, cognitive pretesting, pilot testing and translation into several languages. A targeted literature review of taVNS studies was performed to identify and categorize previously reported AEs and to form item generation. Based on these findings, a semi-structured taVNS Adverse Events Questionnaire (taVNS-AEQ) was developed. Its feasibility and usability were evaluated through cognitive pretesting and pilot testing in a randomized crossover study comparing active and sham taVNS. The literature search initially identified 203 records, of which 71 studies met the predefined eligibility criteria and were included in this review. Among these 71 studies, only 39 provided semi-structured AE data. A total of 539 individual AE symptoms were reported as absolute counts (19 studies), complemented by symptom data assessed using Likert-scales (20 studies), and were categorized for analysis and item generation. In a real-sham crossover study with 29 participants, the most frequent AEs were tingling, fatigue, and changes in concentration. The questionnaire demonstrated good feasibility, and after revisions version 3.0 was translated into four languages. The newly developed semi-structured taVNS-AEQ 3.0 includes four participant items, seven personnel items, and recommendations for documenting stimulation parameters. Current evidence on taVNS-related AEs is limited by the heterogeneous nature of the reporting. The taVNS-AEQ offers a newly developed semi-structured approach to AE assessment, potentially enhancing the quality and comparability of future taVNS studies.Systematic review registration: PROSPERO (Registration Number: CRD420251208237).