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

TY - JOUR

T1 - Does additional monitoring status increase the reporting of adverse drug reactions? An interrupted time series analysis of EudraVigilance data

T2 - An interrupted time series analysis of EudraVigilance data

AU - Segec, A.

AU - Slattery, J.

AU - Morales, D. R.

AU - Januskiene, J.

AU - Kurz, X.

AU - Arlett, P.

N1 - Funding Information: We are grateful to the members of the EMA's Pharmacovigilance Risk Assessment Committee for their comments on the design of this study. We are also grateful to Dr Georgy Genov for helpful comments on the study outline and draft article. The work presented in this article did not receive project funding or grants. Prior postings, sponsors and grants: Partial results were included in the European Commission report7 (which has since been published). DRM has received funding support from the Wellcome Trust, NIHR, Chief Scientist Office and Tenovus Scotland for research unrelated to this work. Publisher Copyright: © 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

KW - additional monitoring

KW - adverse drug reactions

KW - impact

KW - pharmacovigilance

UR - https://www.scopus.com/pages/publications/85097287003

U2 - 10.1002/pds.5174

DO - 10.1002/pds.5174

M3 - Article

C2 - 33197106

SN - 1053-8569

VL - 30

SP - 350

EP - 359

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

IS - 3

ER -