Safety Reporting of Clinical Trials of Investigational Medical Products (CTIMPs) for UK Health Departments’ Research Ethics Service (RES)
Serious adverse reaction
A serious adverse reaction is an untoward and unintended response to an Investigational Medicinal Product (IMP) at any dose, that:
a) results in death;
b) is life-threatening.
c) requires hospitalisation or prolongation of existing hospitalisation;
d) results in persistent or significant disability or incapacity; or
e) consists of a congenital abnormality or birth defect.
An adverse reaction is unexpected if its nature and severity are not consistent with the information about the medicinal product in question set out:
- In the case of a product with marketing authorisation, in the Summary of Product Characteristics for that product
- In the case of any other IMP, in the Investigators Brochure relating to the trial in question
Reporting date for periodic safety reports
| Does the IMP have marketing authorisation in any EU member state? | Reporting date |
| Yes | The International Birth Date for the product |
| No | The date on which any trial of the IMP being conducted by the sponsor was first authorised by a competent authority in any EU member state |
For more detailed guidance, see the European Commission guidance on adverse reaction reporting (ENTR/CT3) .
| Type | Who | When | What | How | To whom |
| Reporting of individual SUSARs | Sponsor, sponsor’s legal representative or Chief Investigator. |
(a) or (b) must be reported within 7 days of the sponsor becoming aware of the event. Any additional information must be reported within 8 days of sending the first report. (c) (d) or (e) must be reported within 15 days of the sponsor becoming aware of the event. |
Any SUSAR in the relevant trial in the UK. |
For CTIMPs not submitted via combined review: email the REC with the RES Safety Report Form (CTIMPs) and SUSAR report enclosed (no form prescribed but should be in the format set out in the current version of ICH Topic E2B – Clinical Safety Data Management). Submit to the MHRA as per the guidance on the MHRA website. For CTIMPs submitted via combined review: submit SUSARs as per MHRA guidance. |
For CTIMPs not submitted via combined review: SUSARs should be submitted to the MHRA and to the REC which issued the favourable ethical opinion. For CTIMPs submitted via combined review: SUSARs should be submitted to the MHRA as per MHRA guidance. The MHRA will liaise with the REC if deemed appropriate. There is no requirement to email the REC. |
| - | Sponsor, sponsor’s legal representative or Chief Investigator. | - | If a SUSAR has occurred in a CTIMP but the SUSAR is not related to the Investigational Medicinal Product (IMP), this does not need to be reported to the MHRA or REC as a SUSAR. | Notify the manufacturer of the IMP. The correspondence should inform the manufacturer what the event was, what circumstances caused it to occur, what the implications for the safety of the study participants were and how these were addressed. All events should be recorded in the Case Report Form/study documentation regardless as to whether they were related to an IMP or to the non-IMP treatment. | Inform the manufacturer of the non-IMP of any significant safety findings. Use of the yellow card scheme is encouraged. |
| Annual safety reporting | Sponsor, sponsor’s legal representative or Chief Investigator. | Annually – within 60 days of reporting date. |
List all worldwide Suspected Serious Adverse Reactions (SSARs) in the reporting period, i.e. both expected and unexpected. Summarise any issues affecting safety of participants. |
For CTIMPs not submitted via combined review: email the REC along with the RES Safety Report Form (CTIMPs). All annual safety reports should be in the format for Development Safety Update Reports (DSUR) set out in the ICH E2F guidelines. For CTIMPs submitted via combined review: DSURs should be submitted via IRAS where at least one of the trials was submitted through combined review. |
For CTIMPs not submitted via combined review: to the MHRA as per the guidance on the MHRA website and to each REC responsible for a trial of the IMP (use separate covering form for each). For CTIMPs submitted via combined review: to the MHRA via IRAS. There is no requirement to separately notify the REC, the MHRA will liaise with the REC if deemed appropriate. |
| Urgent safety measures | Sponsor, sponsor’s legal representative or Chief Investigator. Or exceptionally by local Principal Investigator (PI). | Within 3 days. | Reasons for the urgent safety measures and the plan for further action. |
For studies not submitted via combined review: submit USMs in writing (by email). For CTIMPs submitted via combined review: submit USMs in IRAS. |
For studies that were not submitted via combined review: submit USMs to the MHRA and to the REC which issued the favourable ethical opinion. For CTIMPs submitted via combined review: submit USMs to the MHRA via IRAS. There is no requirement to separately notify the REC, the MHRA will liaise with the REC if deemed appropriate. |