VII.B.2. Principles for the evaluation of the risk-benefit balance within PSURs and scope of the information to be included

Benefit-risk evaluation should be carried out throughout the lifecycle of the medicinal product to promote and protect public health and to enhance patient safety through effective risk minimisation.

After a marketing authorisation is granted, it is necessary to continue evaluating the benefits and risks of medicinal products in actual use and/or long term use, to confirm that the risk-benefit balance remains favourable.

The analysis of the risk-benefit balance should incorporate an evaluation of the safety, efficacy and effectiveness information that becomes available2 , with reasonable and appropriate effort, during the reporting interval for the medicinal product in the context of what was known previously.

The risk evaluation should be based on all uses of the medicinal product. The scope includes evaluation of safety in real medical practice including use in unauthorised indications and use which is not in line with the product information. If use of the medicinal product is identified where there are critical gaps in knowledge for specific safety issues or populations, such use should be reported in the PSUR (e.g. use in paediatric population or in pregnant women). Sources of information on use outside authorisation may include drug utilisation data, information from spontaneous reports and publications in the literature.

The scope of the benefit information should include both clinical trial and real world data in authorised indications.

The integrated benefit-risk evaluation should be performed for all authorised indications and should incorporate the evaluation of risks in all use of the medicinal product (including use in unauthorised indications). The evaluation should involve:

1. Critically examining the information which has emerged during the reporting interval to determine whether it has generated new signals, led to the identification of new potential or identified risks or contributed to knowledge of previously identified risks.
2. Critically summarising relevant new safety, efficacy and effectiveness information that could have an impact on the risk-benefit balance of the medicinal product.
3. Conducting an integrated benefit-risk analysis for all authorised indications based on the cumulative information available since the development international birth date (DIBD), the date of first authorisation for the conduct of an interventional clinical trial in any country. For the cases where the DIBD is unknown or the marketing authorisation holder does not have access to data from the clinical development period, the earliest possible applicable date should be used as starting point for the inclusion and evaluation of the cumulative information.
4. Summarising any risk minimisation actions that may have been taken or implemented during the reporting interval, as well as risk minimisation actions that are planned to be implemented.
5. Outlining plans for signal or risk evaluations including timelines and/or proposals for additional pharmacovigilance activities.