The public believes that governments and regulators will ensure the safety of the medicines they use. This means that efforts to improve available drug safety systems are always high on agendas — particularly as zerorisk medicines do not exist — but this often requires considerable investment in new electronic technologies. To achieve drug safety objectives, greater demands have also been placed on the pharmaceutical industry. Since 1995, for instance, EU regulations have required new drug applications to include details of a risk management system. Following the EU's large expansion in 2004, there was increased emphasis on drug safety in new legislation and a number of Directives touch upon key topics in this area.
Existing systemsThe full extent of medicinal risk is rarely known at the outset of the application; clinical trials are limited in size and feature restrictions in the scope of patients studied, so full information relating to age, gender, ethnicity, restricted co-morbidities and interactions with other medications is impossible at this stage. As such, risk should be managed over a product's lifecycle and reflect the product's use in the wider population. The processes involved in such programmes include risk detection, risk assessment, risk minimisation and risk communication. Because multiple risks may be associated with a product, however, their combined impact in relation to the benefit conferred by the drug must be assessed. The EMA has published guidelines on risk management systems to help companies meet requirements in this area.4
EudraVigilance, a joint effort between the EMA and the competent authorities in member states, is a system that forms an integral part of the European approach to risk management. First developed in 2001, EudraVigilance consists of a data processing network and management system for reporting and evaluating suspected adverse drug reactions across the European Economic Area (EEA). By implementing an electronic approach to pharmacovigilance, the authorities hoped to facilitate early detection of possible safety signals associated with medicines. Data generated cover both the development and postauthorisation periods for products, but some critics of the system worry about an over-reliance on companies to report data that is used in the system.
The EudraVigilance Clinical Trial Module (EVCTM) focuses on the reporting of suspected unexpected serious adverse reactions (SUSARs) during clinical trials. SUSARs from clinical trials must be reported by the trial sponsor to the regulatory body in the country where the event occurred, and it is then that agency's responsibility to electronically report the event to the EudraVigilance system. Study sponsors in the EU must have a EUDRACT number, which functions as a unique identifier of the trial within the EU's clinical trial database. In this way, SUSARs from the same clinical programme being run at different European sites can be collectively assessed and processed. There is also a EudraVigilance Post-Authorisation Module (EVPM) designed for post-authorisation individual case study reports. Similarly with EVCTM, SUSARs must be reported to the national regulatory body, which then electronically reports the event to the EudraVigilance system.
Because drug safety issues have an international dimension, efforts have been made to enable the global exchange of relevant safety information. ICH, for example, brings together regulatory agencies from Europe, the US and Japan, along with their industry counterparts. ICH's technical working groups have produced several guidelines and documents on the secure electronic exchange of safety data for pharmacovigilance and the EudraVigilance system makes use of such safety information if it arises from outside Europe. SUSARs occurring in a trial outside the EEA must be reported electronically to the EudraVigilance system by the sponsor rather than the regulatory agency. A similar responsibility is assigned to companies regarding safety issues occurring outside the EEA for authorised products.