Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar;30(3):350-359.
doi: 10.1002/pds.5174. Epub 2020 Dec 8.

Does additional monitoring status increase the reporting of adverse drug reactions? An interrupted time series analysis of EudraVigilance data

Andrej Segec  1 , Jim Slattery  1 , Daniel R Morales  1   2 , Justina Januskiene  1 , Xavier Kurz  1 , Peter Arlett  1   3
Affiliations

Does additional monitoring status increase the reporting of adverse drug reactions? An interrupted time series analysis of EudraVigilance data

Andrej Segec et al. Pharmacoepidemiol Drug Saf. 2021 Mar.

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.

Keywords: additional monitoring; adverse drug reactions; impact; pharmacovigilance.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

FLOWCHART 1
FLOWCHART 1
Selection of substances for the study. *Count includes valproic acid as one product and does not include denosumab‐Prolia (used as control)
FIGURE 1
FIGURE 1
Interrupted time series analysis. New products included in the study. Reporting of post‐marketing ADRs from the EEA. Green vertical line: addition to AM list. Red line: predicted reporting from seasonality‐adjusted model. Dashed line: de‐seasonalised trend [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Interrupted time series analysis. Products included in the study due to the requirement to conduct a PASS. Reporting of post‐marketing ADRs from the EEA. Green vertical line: addition to AM list. Red line: predicted reporting from seasonality‐adjusted model. Dashed line: de‐seasonalised trend [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Joinpoint regression analysis—new products included in the study. Reporting of post‐marketing ADRs from the EEA, addition to AM list is at time point 12 (time in months) [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 4
FIGURE 4
Joinpoint regression analysis—products included in the study due to PASS requirement. Reporting of post‐marketing ADRs from the EEA, addition to AM list is at time point 12 (time in months) [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

References

    1. Januskiene J, Segec A, Slattery JM, et al. What are the patients' and health care professionals' understanding and behaviors towards adverse drug reaction reporting and additional monitoring? Pharmacoepidemiol Drug Saf. 2020 Oct 25. 10.1111/ans.15099. - DOI - PMC - PubMed
    1. Regulation (EC) No 726/2004 of the European Parliament and of the council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, Official Journal L – 136, 30/04/2004, p. 1–33. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex:02004R0726-201.... Accessed April 30, 2019.
    1. European Medicines Agency . List of medicines subject to additional monitoring, EMA/245297/2013 Rev.60. https://www.ema.europa.eu/en/human-regulatory/post-authorisation/pharmac.... Accessed January 17, 2020.
    1. European Medicines Agency . Guideline on good pharmacovigilance practices Module X – additional monitoring. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guidelin.... Accessed April 30, 2019.
    1. Goedecke T, Morales DR, Pacurariu A, Kurz X. Measuring the impact of medicines regulatory interventions—systematic review and methodological considerations. Br J Clin Pharmacol. 2018;84(3):419‐433. - PMC - PubMed

MeSH terms