Abstract
PURPOSE: To evaluate the impact of including a medicine in the list of medicinal products subject to additional monitoring (AM) on the reporting of adverse drug reactions (ADRs) in the european economic area (EEA). METHODS: Interrupted time series using the monthly number of EEA ADR reports in EudraVigilance during 12 months before and after the addition to AM list. The main outcome was the change (%) in reporting of ADRs with step change as the a priori impact model. Further time series analysis was performed using Joinpoint Regression. RESULTS: The analysis included 11 active substances. No significant immediate (step change) increase of reporting was identified for any product at time of addition to AM list. We identified a significant gradual increase of ADR reporting after addition to AM list (slope change) for two out of five new products-boceprevir (10% per month, 95% confidence interval (CI) 3%-18%) and denosumab-Xgeva (13% per month, 95% CI 4%-22%). No change was identified for Prolia, another denosumab-containing product not subject to AM. No significant increase was identified for any product included in the AM list due to the requirement to conduct a PASS. Conversely, a gradual decrease in reporting was identified for natalizumab (-5% per month; 95% CI -10% to -1%), rivaroxaban (-5%; -8 to -3%), and varenicline (-16%; -21 to -10%). The results were corroborated by the Joinpoint analyses, which yielded similar results. CONCLUSIONS: We identified limited evidence that reporting of ADRs increased modestly and gradually for some new products and not for products with PASS requirement.