ASR

The first ASR should cover the period from the authorisation date of the trial (not from the start date of the trial) up to one year later. For example, if the study is approved on 15 January 2025, the first ASR covers the period from 15 January 2026 up to and including 14 January 2027. The second ASR then covers the period from 15 January 2027 up to and including 14 January 2028, and so on.

If there is a deviation from this period, this, together with the reason, should be described in the introduction of the ASR or in an attached cover letter. The period of an ASR should never be longer than one year.

An ASR should be submitted no later than 60 days after the ‘Data Lock Point’. The ‘Data Lock Point’ is the last day of the period covered by the ASR. The submission date of the ASR cannot be the same date as the date on which the ASR expires. Therefore, after the Data Lock Point, there are 60 days to write and submit the ASR.

For all studies approved under the CTR, region-specific information as stated in question 7.45 of the CTR Q&A should be included. This concerns:

• A cumulative overview of the SARs (Serious Adverse Reactions) reported from the trial authorisation date up to and including the end date of the ASR.
• A list of participants who died during the period covered by the ASR, including case number, assigned treatment, cause of death, and causality to the IMP.
• A list of participants who discontinued the study due to an Adverse Event (AE), including case number, assigned treatment, description of the event (‘Preferred MedDRA term’), and causality to the IMP.
• Safety signals (when the ASR is written for an IMP developed by a non-commercial sponsor).

Yes, you can use the simplified template, since the headings in the template are based on the ICH E2F guideline. However, in this case, the entire template should be completed, and the example text cannot simply be adopted. Therefore, information should also be entered if the template indicates ‘Not applicable’ or ‘If applicable’, or it should be explained why the section is not applicable.

No, the RSI determines which adverse events should be reported as SUSARs in EudraVigilance. Therefore, an RSI is not the same as the safety profile of an investigational medicinal product or the investigator information. The RSI should be located in one place in the study dossier (as a separate section in the IB or section 4.8 of the SmPC) and must be approved before it is being used.

Referring to multiple versions of the RSI is permitted. If multiple RSI were effective during the period covered by the ASR, all versions used should be described in the ASR. The RSIs should either be added as an appendix to the ASR or added as separate documents in CTIS. More information about the RSI can be found in the Q&A CTR questions 7.8 to 7.21.

If the SmPC does not contain a version number and/or date, as is the case for example with the European product information on the EMA website, the date of the last update should be indicated. This date is located on the EMA website on the product overview page and not in the PDF document itself.

No, it is not necessary to include comparable studies from public registers in section 5 of the ASR. Data from other studies that are relevant to the study covered by the ASR should be included in section 10 ‘Other clinical trial/study safety information’ or section 13 ‘Literature’ of the ASR.

Unfortunately, no alert or notification is generated for an ASR RFI in the ‘notices & alerts’ tab in CTIS, although this is described as such in the CTIS Sponsor Handbook. A video tutorial is available showing where the RFI can be found and how to respond to it.

To submit an ASR and respond to ASR RFIs, an ‘ASR submitter’ role is required. It is important to assign this role to multiple persons so that an RFI can be answered on time in the absence of the submitter. The ‘CT Admin’ role cannot view or answer ASR RFIs.