Reporter vs Marketing Authorization Holder in Seriousness Assessment of Adverse Drug Reactions for Insulin Preparations: A Retrospective Analysis

INTRODUCTION. Inconsistent assessment of adverse drug reaction (ADR) remains a relevant pharmacovigilance challenge, particularly regarding insulin biosimilars widely used in the medical practice. This is especially critical for ADRs associated with the pharmacological effects of insulin (hypo- and hyperglycemia) and hypersensitivity reactions, frequently classified as serious due to a lack of adequate clinical context. This discrepancy reduces analytical value of the available data and results in consequent accumulation of inaccurate safety data on a medicinal product.

AIM. This study aimed to identify quality improvement approaches to data provided in spontaneous reports and to compare the assessment of ADR seriousness for insulin preparations (insulin aspart, insulin lispro, and insulin glargine) performed by reporters and by pharmacovigilance department of the marketing authorization holder.

MATERIALS AND METHODS. A retrospective observational study was conducted using spontaneous ADR reports submitted since the registration of insulin aspart, insulin lispro, and insulin glargine manufactured in the Russian Federation (2021–2024, GEROPHARM LLC). Valid cases were coded using MedDRA v.25.1 and then analyzed. Seriousness criteria were defined according to ICH E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting and the EAEU Good Pharmacovigilance Practice. Descriptive statistics and comparative analysis of MedDRA Preferred Terms were applied.

RESULTS. Significant discrepancies were identified: assessments by reporters and marketing authorization holder matched only in 41.3% of cases, while 58.7% demonstrated inconsistency. In 99.6% of the latter cases, reporters classified ADRs as serious, while marketing authorization holder assigned them as non-serious. The most disputable criteria selected by reporters were Important Medical Events (71.1% of all discrepancies) and Life-Threatening Events (25.0%). Disagreements predominantly involved ADRs related to pharmacological effects of insulins and hypersensitivity reactions. More than half of the spontaneous reports contained insufficient information, limiting the accuracy of medical assessment.

CONCLUSIONS. The substantial differences in seriousness assessment may be associated with insufficient quality and completeness of the submitted data, frequent use of subjective criteria (such as Life-Threatening and Important Medical Event), and persistent skepticism about biosimilar insulin products. Improving pharmacovigilance accuracy requires educational initiatives and measures aimed at enhancing the quality of spontaneous ADR reporting.

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