(P-528) Measuring the Impact of Marketing Authorisation Withdrawal and Revocation on Public Health in France, Germany and UK

Background: Impact of pharmacovigilance actions such as marketing authorisation (MA) withdrawal on public health (PH) is not normally measured quantitatively. Removing a medicine from market may benefit PH by avoiding adverse drug reactions (ADRs), which should be measured quantitatively if possible.

Objectives: To quantify impact of MA withdrawals/revocations in terms of changes in morbidity and mortality.

Methods: MA withdrawals/revocations for prescription medicines for post-marketing safety reasons in Europe between July 2012 and December 2016 were identified. For each product, patients exposed to these medicines were counted for 12 months pre- and post-MA withdrawal/revocation, in IQVIA Medical Research Data (IMRD)-France, -Germany and THIN electronic health record database in the UK. Annual exposure was estimated for each. Reasons for regulatory action (ADRs of interest) were obtained from EMA records for each medicine. We conducted a systematic review for publications which quantified the ADRs of interest prior to regulatory action, allowing estimation of risk in exposed patients. PH impact, expressed as the annual number of ADRs avoided due to PV action, was estimated by modelling exposure and ADR risk. Background risk was used to put results into context.

Results: Four MA withdrawals and 2 revocations for safety reasons in France, Germany and/or UK met inclusion criteria for the study. Usage of each product decreased following MA withdrawal/revocation. Risk for ADRs of interest prior to PV action ranged from 0.1% to 41.25%. To estimate the impact of each withdrawal/revocation, average annual exposure of the medicine within each IMRD or THIN population was multiplied by the risk to give the crude number of ADRs expected to be avoided annually as a result of the regulatory action. Estimates ranged from 3 cases per year of new-onset diabetes mellitus avoided in the THIN population following withdrawal of nicotinic acid/laropiprant, to 1,464 cases per year of severe hypotension avoided amongst IMRD-France patients due to meprobamate withdrawal.

Conclusions: This new model quantifies the PH impact of MA withdrawal and revocation in terms of serious morbidity, as exposure to all included medicines was reduced or eliminated. The method can be applied to products in other settings and allows measurement of impact of decisions for product withdrawals/revocations.