Pharmacovigilance and Drug Safety

Archive for the ‘reporting’ Category

PSURs are a regulatory requirement for authorised medicines in the EU and some other countries. They are generated by companies for each of their products at specified intervals – in the EU every 6 months for the first 2 years of marketing, then annually until the first renewal (at 4.5 years) and then every 3 years.

The PSUR provides an overview of the safety of the product, and includes all ADRs reported in the period since the last PSUR, together with a summary of the registration status of the product worldwide, actions taken for safety reasons, the worldwide usage of the product and an analysis of safety. The PSUR gives an opportunity for review of benefits and risks at intervals. Their preparation involves significant work by companies and the timing of their submission and content is subject to the regulations. Analogous documents are required for clinical trials –Annual Safety Reports covering every study on each investigational product.

Spontaneous reporting

This is the reporting by healthcare professionals (and in some countries, patients, relatives and others) “spontaneously” of their suspicion of an adverse reaction having occurred. The reporting might be directly to the company marketing the product, or it could be made to the regulatory authority. If there has been spontaneous reporting of a suspected ADR to a pharmaceutical company (including reporting to any employee, such as sales representatives or to contractors) there are legal obligations on the company to report serious reactions within a specified time frame to the regulatory authority (“expedited reporting). This takes place to the authorities in that country where the report was received and possibly to other regulatory authorities also. For non-serious reactions, reports usually have to be included in periodic safety update reports (see below).

In addition, the pharmaceutical company has to identify reports of adverse reactions published in the medical and scientific literature (by a process of weekly “literature screening”) and cases must be reported by the company in a similar way to the regulatory authorities.

The authorities in turn are required to report to each company anonymised information on the serious adverse reactions that they have received in relation to that company’s marketed products. There are also requirements for companies to report spontaneous cases of serious adverse reactions that they have received from certain regulatory authorities to their own authorities. There are mechanisms in place to identify and remove duplicate reports.

All these cases – ‘Individual Case Safety Reports’ (ICSRs) – are entered on the company’s safety database and on the regulatory authority’s safety database. They are examined individually and in the aggregate for a product in order to identify clusters of reports that could represent a signal of a previously unknown adverse reaction or drug interaction or some change in the character of a known adverse reaction. It may also be possible to recognise a new risk factor for a reaction to a product, such as a sub-group of patients at particular risk.

The main limitation of spontaneous reporting schemes is that there is under-reporting of adverse reactions, as in most countries the process for the initial reporter (i.e. the healthcare professional) is voluntary and unpaid. However, their main purpose is not the quantification of the frequency of adverse reactions, but the identification of signals.

In addition to the national regulatory agency databases of spontaneous reports and the company databases, there are two over-arching international databases. The EMEA maintains the EUDRAVIGILANCE safety database, including ICSRs received from all companies with products marketed in the European Economic Area, reports received by the national regulatory agencies in the EEA, and serious cases from clinical trials. This database is linked electronically to the national regulatory agency databases and exchanges data with them and with the company databases electronically.

In addition, the World Health Organization operates a global scheme involving national collaborating centres (most of the national regulatory agencies worldwide) and a coordinating centre in Sweden – the Uppsala Monitoring Centre (UMC). The regulatory authorities send the UMC all serious adverse reaction reports that they have received. The UMC database (“Vigibase”) is the only database in the world that includes all the regulatory authority and company ADR reports. The UMC has a panel of independent experts who review the data for signals of new adverse reactions. Aggregate data from Vigibase are made available to pharmaceutical companies for purchase.