Saad Shakir writes:
“The 2012 EU pharmacovigilance legislation made it necessary in some cases to conduct a Post Authorisation Safety Study (PASS) in several European countries. While it is clearly unnecessary to conduct such studies in all 28 member states of the EU, they usually need to be conducted in a number of countries, perhaps four or five. The EMA’s pharmacovigilance committee, PRAC, and Member State rapporteurs expect some risk management and risk minimisation studies to be conducted in such a way. The DSRU has built up experience of co-ordinating and conducting PASS studies in a network of several European countries.
The “network of studies” is established by initially identifying research units in multiple European countries that have data sources capable of answering the research question and that can work together. A “grand” protocol is written which aims to convert the requirements of risk management into a specific research question(s), specify exposure and outcome definitions, as well as list possible confounding factors. Then each network partner writes their own protocol applying as much as possible (ideally everything) from the grand protocol. However, because of the diversity of data available in secondary use databases and other practical considerations, not every partner can apply the grand protocol, but the aim is to achieve as much alignment as possible.
The network’s grand protocol is submitted to PRAC and the rapporteurs, with each individual partner protocol included as an appendix. A statistical analysis plan is also written a priori.
The analysis of the network studies depends on the nature of the study and the expected results. Depending on the characteristics of the data and their analysis a meta-analysis or pooling of the results is undertaken.
One partner acts as the co-ordinating unit and is responsible for writing the grand protocol, co-ordinating the development of the partners’ protocols and interfacing with the marketing authorisation holder and the regulatory authority. The co-ordinating unit also manages the writing of accrual reports, interim reports, updates for Risk Management Plans, the final study report and publications.
The advantages of these European Network studies are many. They include conducting PASS studies in several EU countries with their different health care systems, increasing the sample size and providing assurance that risk management and risk minimisation are working in a number of member states.
The EU network studies provide a way forward to integrating pharmacovigilance across the EU.”