Use notifications for lifecycle events, not as a substitute for a modification
The normal workflow is to submit the lifecycle event through the Trial & Recruitment Periods area. The main restart exception is a temporary halt whose reasons had the potential to affect the benefit-risk balance. In that case, Article 38 requires the restart to be authorised through a substantial modification before the sponsor submits the restart notification.
Lifecycle notification matrix
First act of recruitment of a potential subject unless the protocol defines the start differently. EMA describes the operational CTIS event as initiation of the first trial site in the Member State concerned. Notify within 15 days.
First visit of the first subject in the Member State concerned. Notify within 15 days. Recruitment must start within two years of authorisation unless an extension is authorised through a substantial modification.
The date recruitment stops in the Member State concerned. EMA describes this as the date on which the last patient is enrolled in that Member State. Notify within 15 days.
An interruption not provided for in the protocol where the sponsor intends to resume the trial. Notify within 15 days. If the reason concerns participant safety, notify without undue delay and no later than 15 days, with the reasons and follow-up measures.
If the reasons for the halt had no potential effect on the benefit-risk balance, notify the restart within 15 days of resumption.
If the reasons for the halt had the potential to affect the benefit-risk balance, request the restart through a substantial modification first. Submit the restart notification only after authorisation.
Notify the restart of recruitment within 15 days. The trial itself must be restarted before recruitment can restart.
Premature end before the protocol-defined conditions are accomplished. Notify within 15 days when benefit-risk is not affected. If benefit-risk is affected, notify without undue delay and no later than 15 days, with reasons and follow-up measures.
The last visit of the last subject, or a later point defined in the protocol. Notify the relevant Member State concerned within 15 days.
If the trial also ran outside the EEA, notify the global end after the trial ends in the last country in which it was conducted. The CTR requires notification within 15 days.
Notification or substantial modification?
Start, recruitment event, temporary halt, restart, early termination or end normally starts in the notification workflow.
If the reasons had no potential effect on the benefit-risk balance, use the restart notification route.
Submit the restart request through a substantial modification and wait for authorisation before restarting.
After the applicable event occurs, record it in CTIS within the required timing.
For the broader classification test, use the substantial vs non-substantial modification guide.
Country scope matters
Trial and recruitment events can occur on different dates in different Member States. CTIS lets the sponsor select the relevant Member State or States when entering Trial & Recruitment Periods information. If the same event date applies to several Member States, the current Sponsor Handbook allows them to be selected together.
Do not copy an EU-wide programme date into a country notification unless the lifecycle event actually occurred on that date in that Member State.
Who can prepare and submit notifications
Can perform the notification workflow within the user's authorised trial scope.
Can prepare and submit lifecycle notifications.
Can prepare a notification but cannot submit it.
Write structured notification text for a public record
Lifecycle notifications affect the CTIS trial record. EMA guidance warns specifically that temporary-halt structured data can become publicly available. Avoid placing personal data or commercially confidential information in public structured fields.
If a notification is later corrected or withdrawn, preserve a clear internal record of the original event, the reason for the correction and the final lifecycle sequence.
End-of-trial notification is not the results submission
The notification records that the trial reached the relevant end event. Final results and the layperson summary follow under a separate CTIS workflow and timetable.
Continue with Ending a trial and submitting results in CTIS for the closure-to-disclosure sequence.
Official sources and resources
- EMA CTIS Sponsor Handbook, version 6.4, section 4.1 on trial and recruitment-period notifications.
- Regulation (EU) No 536/2014, Articles 36 to 38.
- European Commission EudraLex Volume 10, including the July 2026 CTR Questions & Answers.
- CCMO: Temporary halt and restart.
Last reviewed: 19 September 2026