- Revisions in VI.A.2.1.1. (Causality), VI.A.2.4. (Seriousness), VI.B.1.2. (Solicited reports), VI.B.3. (Follow-up of reports), VI.B.6.3. (Reports of overdose, abuse, off-label use, misuse, medication error or occupational exposure), VI.C.1. (Reporting rules for clinical trials and post-authorisation studies in the EU), VI.C.2.2.2. (Solicited reports), VI.C.188.8.131.52. (Reports of suspected adverse reactions originating from organised data collection systems and other systems)
- Clarifications on the clock start for the reporting of valid ICSRs in VI.B.7
- Clarifications on the handling of ICSRs when reported in an official language in VI.C.184.108.40.206
- Replacements of tables highlighting interim arrangements applicable to marketing authorisation holders in VI.App.3.1.1
- Correction in VI.C.2.2.9. (Period during a public health emergency)
Primary versus Secondary Data Collection:
- Non-interventional post-authorisation studies should be distinguished between those with primary data collection directly from healthcare professionals or consumers and study designs which are based on the secondary use of data. Depending on the study design, the requirements provided hereafter apply.
- In case of doubt, the reporting requirements should be clarified with the concerned competent authorities in Member States. National legislation should be followed as applicable regarding the obligations towards local ethics committees.
Impact on Non-Interventional Post-Authorisation Studies with Primary Data Collection:
- Information on all adverse events should be collected from healthcare professionals or consumers in the course of the study unless the protocol provides differently with a due justification for not collecting certain adverse events. For all collected adverse events, comprehensive and high quality information should be sought in a manner which allow for valid ICSRs to be reported within the appropriate timeframes
- A system should be put in place to record and document complete and comprehensive case information on solicited adverse events which need to be collected
- These adverse events should be systematically assessed to determine whether they are possibly related to the studied (or supplied) medicinal products
- A method of causality assessment should be applied for assessing the causal role of the studied (or supplied) medicinal products in the solicited adverse events
- An adverse event should be classified as an adverse reaction, if there is at least a reasonable possibility of causal relationship
- Only valid ICSRs of adverse reactions, which are suspected to be related to the studied (or supplied) medicinal product by the primary source or the receiver of the case, should be reported in accordance with the requirements
- In certain circumstances, fatal outcome may not be subject to expedited reporting as ICSRs. A justification should always be provided in the protocol
- All fatal outcomes should be considered as adverse events which should be collected. In certain circumstances, suspected adverse reactions with fatal outcome may not be subject to expedited reporting as ICSRs, for example because they refer to study outcomes (efficacy end points), because the patients included in the study have a disease with high mortality, or because the fatal outcomes have no relation to the objective of the study. For these particular situations, the rational for not reporting certain adverse reactions with fatal outcomes should be clearly described in the protocol.
- Other reports of adverse events should be summarised as part of any interim safety analysis and in the final study report, where applicable
- In situations where adverse reactions are suspected to be related to medicinal products other than the studied (or supplied) medicine, these reports should be managed, classified and reported as spontaneous ICSRs. They should be notified by the primary source to the competent authority in the Member State where the reactions occurred or to the marketing authorisation holder of the suspected medicinal product, but not to both (to avoid duplicate reporting).
- For adverse events for which the protocol provides differently and does not require their systematic collection, healthcare professionals and consumers should be informed in the protocol (or other study documents) of the possibility to report adverse reactions (for which they suspect a causal role of a medicine) to the marketing authorisation holder of the suspected medicinal product (studied or not) or to the concerned competent authorities via the national spontaneous reporting system. Valid ICSRs should be managed, classified and reported as spontaneous by the receiver of the reports. When made aware of them, these reports should also be summarised in the relevant study reports.
- Note: New requirements for non-interventional post-authorisation studies will become mandatory for any new study started after 01-JAN-2015. Implementation for new or ongoing studies started before that date is optional
Requirements for Non-Interventional Post-Authorisation Studies with Secondary Data Collection:
- The design of such studies is characterised by the secondary use of data previously collected from consumers or healthcare professionals for other purposes. Examples include medical chart reviews (including following-up on data with healthcare professionals), analysis of electronic healthcare records, systematic reviews, meta-analyses.
- For these studies, the reporting of suspected adverse reactions in the form of ICSRs is not required. Reports of adverse events/reactions should be summarised as part of any interim safety analysis and in the final study report unless the protocol provides for different reporting.