Comparative Pharmacovigilance: Herbal vs. Conventional Medicines in Adverse Events

Thesis Abstract

This study addresses the persistent challenge of comparative pharmacovigilance by examining adverse event profiles associated with herbal medicines versus conventional pharmaceutical products, aiming to determine differential safety signals, under-reporting patterns, and risk factors that influence adverse outcomes in real-world use. The central aim is to evaluate and contrast the incidence, severity, and causality of adverse events (AEs) reported for herbal and conventional medicines across a defined population, with a focus on identifying modifiable determinants and informing regulatory and clinical decision-making. Specific objectives include (1) estimating the incidence rate of AEs for herbal versus conventional medicines in a representative patient cohort; (2) characterizing the severity, seriousness, onset, and outcome of AEs by medicine class; (3) assessing reporting completeness and under-reporting patterns using capture–recapture and discrete choice modeling; (4) identifying patient- and product-level risk factors through multivariate regression analyses; (5) exploring patient perceptions, beliefs, and reporting drivers via thematic analysis of patient and healthcare professional narratives; and (6) evaluating the predictive value of two theoretical frameworks—the Safety Signal Theory and the Pharmacovigilance Risk Stratification Model—in explaining AE occurrence and reporting behavior. A mixed-methods, cross-sectional design is employed, encompassing a quantitative arm with retrospective pharmacovigilance data from 2018–2023 and a qualitative arm involving semi-structured interviews. The quantitative component analyzes 15,000 anonymized AE reports retrieved from national pharmacovigilance databases, including 7,500 herbal-related reports and 7,500 conventional-drug reports, applying descriptive statistics, incidence rate calculations, chi-square tests for categorical comparisons, and multivariable logistic regression to identify independent predictors of serious AEs and likelihood of report submission. The qualitative component conducts 40 in-depth interviews with patients, 20 with prescribers, and 10 with pharmacovigilance professionals, followed by thematic analysis to extract nuanced insights into reporting motivations, recognition of herb–drug interactions, and barriers to AE reporting. Validity and reliability are ensured through triangulation of data sources, instrument piloting, inter-coder reliability checks (Cohen’s kappa > 0.70), and sensitivity analyses with alternative model specifications. Analytical techniques include regression-based modeling for AE risk, survival analysis for time-to-onset of AEs, and thematic coding grounded in Safety Signal Theory and the Pharmacovigilance Risk Stratification Model, complemented by curvature tests to assess non-linear effects. Expected findings anticipate higher under-reporting rates for herbal AEs due to perceptions of safety, with comparable or lower incidence rates of severe AEs for conventional medicines, but a greater likelihood of drug–herb interactions contributing to serious outcomes in specific therapeutic areas. The study also expects to identify demographic and pharmacological factors—age, polypharmacy, comorbidity burden, and use of over-the-counter herbal supplements—as significant predictors of AE risk, and to reveal gaps in reporting completeness linked to healthcare access and literacy. The contribution to knowledge includes advancing empirical evidence on relative safety signals between herbal and conventional medicines, informing regulatory risk assessment, and guiding clinical monitoring strategies and patient education to improve AE detection and reporting. The study concludes that integrated pharmacovigilance frameworks combining quantitative signal detection with qualitative insights are essential to capture the complexities of herbal medicine safety alongside conventional therapies. Recommendations emphasize strengthened post-marketing surveillance for herbal products, standardized adverse event terminologies across medicine classes, active pharmacovigilance partnerships with traditional healers and herbal practitioners, and targeted educational interventions to enhance reporting behavior among patients and clinicians.