مقایسه اداره غذا و دارو(FDA) و پیاده سازی مدیریت ریسک آژانس داروهای اروپا برای مصوبات اخیر دارویی : گزارش از جامعه بین المللی برای اقتصاد شرکت دارویی و نتایج تحقیقات گروه کاری مدیریت سود ریسک

Objective 1) To compare the Food and Drug Administration’s (FDA’s) Risk Evaluation and Mitigation Strategies (REMS) and European Medicines Agency’s (EMA’s) Risk Management Plan (RMP) guidances and 2) to compare REMS and RMPs for specific chemical entities and biological products. Methods FDA, EMA, and pharmaceutical company Web sites were consulted for details pertaining to REMS and RMPs. REMS requirements include medication guides, communication plans, elements to ensure safe use, implementation systems, and specified assessment intervals. RMP requirements are increased pharmacovigilance and risk minimization activities. We compared these requirements for drugs requiring both REMS and RMPs. Results We identified 95 drugs on FDA’s REMS list as of March 2010. Of these, there were 29 drugs (11 biologics and 18 new chemical entities) with EMA RMPs. REMS and RMPs are similar in objectives, with comparable toolkits. Both allow flexibility in product-specific actions, recognizing adverse effects of potential concern. Of the 29 drugs reviewed, REMS requirements not included in RMPs were patient medication guides (100% of the drugs), provider communication plans (38%), and routine monitoring of REMS (66%). RMP requirements not included in REMS were specific adverse event reporting (45% of the drugs), prospective registry studies (34%), prospective epidemiology studies (24%), additional trial data (28%), and Summary of Product Characteristics contraindications (76%). Conclusions Both REMS and RMPs provide positive guidance for identification, monitoring, and minimization of risk to patient safety. Currently, neither agency provides specific guidance on how risk should be related to benefit either qualitatively or quantitatively.

Partly in response to the withdrawal of high-profile branded drugs such as Vioxx [1], Seldane [2], Rezulin [3], Propulsid, Baycol [4], and Lotronex [5] over the last few years, regulatory authorities have changed emphasis from the reactive collection of safety data to a more proactive risk management approach. Public scrutiny of regulatory bodies has also increased the focus on drug safety surveillance with the downstream impact of increased regulatory requirements for postmarketing pharmacovigilance. From discussions on potential approaches for establishing acceptable methodologies for quantitative benefit-risk assessment, both European and US constituents determined that transparency and consistency were required, as well as flexibility in judgment [6] and [7]. The European Medicines Agency (EMA) has issued a reflection paper [6] and initiated a benefit-risk methodology project aimed at making the assessment of risks and benefits of medicines more consistent and transparent. The U.S. Food and Drug Administration (FDA) is also working on providing a framework to facilitate a more structured approach to risk-benefit assessment [8]. The FDA identifies risk management as an iterative process designed to optimize the benefit-risk balance for regulated products throughout the product life cycle [9]. In March 2005, the FDA issued three guidance documents that defined the formal basis of risk management. These were Premarketing Risk Assessment [10], Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment [11], and the Development and Use of Risk Minimization Action Plans (RiskMAPs) [12]. These three documents subsequently provided the building blocks for the more recent Risk Evaluation and Mitigation Strategies (REMS) [13]. The final content of a product’s REMS, however, reflects the unique mix of product attributes as well as the intended prescriber and patient populations. For several years, the focus by the EMA has been directed toward a proactive approach in ensuring patient safety, while continuing efforts to further improve the spontaneous reporting scheme. This resulted in a number of legislative changes in 2005 and the introduction of new tools including the concept of Risk Management Plans (RMPs) [14]. In September 2008, the EMA issued guidelines on risk management systems, a template for an RMP, and new regulations governing pharmacovigilance [15]. The EMA emphasizes the importance of having pharmacovigilance systems in place and mandates the creation of the position of a Qualified Person for Pharmacovigilance to be responsible for a company’s pharmacovigilance efforts for marketed products. Much of the emphasis is placed on databases and reporting systems, especially for postmarketing; however, different EMA member states have taken varying approaches to the collection and reporting of safety data [15]. In summary, through REMS and RMPs, both the FDA and the EMA require proactive approaches for drug safety surveillance. As a result, they have reframed the traditional business model of the pharmaceutical industry.

Both REMS and RMPs provide positive guidance for identification, monitoring, and minimization of risk to patient safety. They do differ on elements such as the monitoring of the implementation of risk minimization actions and the reporting time requirements. Currently, neither agency provides specific guidance on how risk should be related to benefit either qualitatively or quantitatively. The authors recommend that this review exercise should be repeated in 2013 to detect any new trends or threats to the current degree of harmony between the approaches of the FDA and the EMA and to examine what progress, if any, is being made in the development and implementation of quantitative risk and benefit approaches.