A Descriptive Study of Additional Risk Minimization Measures Included in Risk Management Plans Reviewed by the United Kingdom Regulatory Authority

摘要

Background Risk management plans (RMPs) describe known and potential safety concerns with medicines, how they will be studied further and how the risks will be minimized. Since 2005, European legislation has required RMPs to be submitted with applications for marketing authorizations for new medicines and they can also be requested if safety concerns arise post-authorization. Currently, there is limited information published on experience with RMPs. This study investigated the application of 'additional' risk minimization measures (ARMMs), which are those beyond routine product information, looking at all RMPs submitted to the UK regulatory authority during a 5-year period. Objective The aim of this article is to describe when ARMMs are successfully approved by the Medicines and Healthcare products Regulatory Agency (MHRA) according to the type of product, risks and measures included in the plan, and to identify common problems with ARMMs included in RMPs from a regulatory perspective. Methods In this study, all 225 plans assessed by the MHRA between November 2005 and January 2011 were analysed retrospectively. The RMPs and MHRA assessment reports were reviewed and information was classified using pre-defined categories: type of product, reason for the ARMM, type of safety concern, type of ARMM, type of auditing measure to assess the effectiveness of the ARMM and the MHRA assessment and comments on the plan. Results Ninety-five (42%) of 225 RMPs assessed by the MHRA included ARMMs. ARMMs were used more frequently for biological than chemical products (47 vs. 40%). The most common forms of ARMMs were educational materials for healthcare professionals (61%). These were commonly used in RMPs for all types of products and more frequently used for high-risk medicines such as biological products. MHRA regulatory review had an important impact on the content of the plans; 75% required amendments. Inadequate auditing measures, which are tools to assess the effectiveness of each additional risk minimization measure, were a common problem with ARMMs and 24% of those submitted did not include any form of auditing measure. A further 23% were refused because the auditing measures included were not appropriate. Conclusion ARMMs and their related auditing measures are important factors in designing RMPs and achieving regulatory approval. It is usual for an RMP with ARMMs to require revisions prior to approval and this should be factored in to the marketing authorization application process. The type of product, type of risks and target audience should all be considered when designing a successful risk minimization strategy and the RMP needs to be individually customized accordingly.