SUSAR Reporting: Suspected, Unexpected, Serious, and the Clocks That Follow

At a glance

• A SUSAR is the intersection of three conditions: suspected (a reasonable possibility the drug caused it), unexpected (not consistent with the reference safety information), and serious. Miss any one and it is not a SUSAR.
• Expectedness is judged against the reference safety information (RSI) in force at the time the event occurred. A change to the RSI changes what counts as a SUSAR.
• The clocks are the same shape across jurisdictions: 7 calendar days for a fatal or life-threatening SUSAR, 15 days for the rest. The EU adds an 8-day follow-up window after a 7-day report.
• The recipients differ by region. In the EU, the competent authorities, the ethics committee, and the investigators. In the US, FDA via an IND safety report, with the sponsor informing investigators and the IRB.
• All SUSARs are SAEs, but not all SAEs are SUSARs. The filter is unexpectedness and causality, and getting that filter wrong is how teams over- or under-report.

The three-part test

SUSAR stands for suspected unexpected serious adverse reaction, and the name is the definition. All three conditions must hold at once.

Serious is the defined outcome category (death, life-threatening, hospitalisation or its prolongation, persistent or significant disability, congenital anomaly). Suspected means causality: the term “reaction” carries the requirement that a causal relationship between the drug and the event is at least a reasonable possibility (ICH E2A, basic terms). Unexpected is the discriminator that separates a SUSAR from a routine SAE. ICH E2A makes the combined trigger explicit: all adverse drug reactions that are both serious and unexpected are subject to expedited reporting (ICH E2A, single cases of serious, unexpected ADRs). So the chain is: serious event, with a reasonable possibility of drug causation, that is also unexpected. That is a SUSAR. Remove unexpectedness and you have an expected serious reaction, which is documented and reported periodically, not expedited.

Expectedness lives in the RSI, and the RSI is a moving target

“Unexpected” is not a clinical opinion; it is a comparison against a specific document. EU guidance defines an unexpected adverse reaction as one whose nature or severity is not consistent with the applicable product information (EU CT-3, definition of unexpected adverse reaction). That product information is the reference safety information. The expectedness of an adverse reaction is determined by the sponsor in the reference safety information, and for SUSAR reporting the version of the RSI at the moment of occurrence of the SUSAR applies (EU CT-3, reference safety information).

Two practical consequences follow. First, the same event can be a SUSAR in one trial and not in another, because the RSI differs. Second, when the RSI is updated, the population of reportable SUSARs shifts with it. Teams that treat expectedness as a fixed clinical judgment, rather than a comparison against the RSI version in force at the time, mis-sort cases in both directions.

The clocks: 7 days, 15 days, and the EU follow-up

The reporting windows are consistent in shape across the major frameworks. For the most urgent cases, the US rule is that any unexpected fatal or life-threatening suspected adverse reaction must be reported to FDA no later than 7 calendar days after the sponsor’s initial receipt of the information (FDA IND safety reporting, §312.32(c)(2)). The EU sets the same 7-day clock and adds a follow-up window: relevant information about SUSARs that are fatal or life-threatening must be recorded and reported as soon as possible to the competent authorities in all Member States concerned and to the ethics committee, and in any case no later than 7 days after the sponsor’s knowledge, with relevant follow-up information communicated within an additional 8 days; all other SUSARs must be reported within a maximum of 15 days of first knowledge by the sponsor (EU CT-3, reporting timelines). ICH E2A states the 15-day rule for the non-urgent case in the same terms: serious, unexpected reactions that are not fatal or life-threatening must be filed as soon as possible but no later than 15 calendar days (ICH E2A, reporting time frames).

SUSAR type	Clock	Note
Fatal or life-threatening	7 calendar days	EU adds 8-day follow-up after the initial report
All other SUSARs	15 calendar days	From first knowledge by the sponsor

The frameworks align by design; EU guidance is written to be read in conjunction with ICH E2A, and FDA’s causality standard is explicitly consistent with E2A. The differences are jurisdictional mechanics, not conflicting requirements.

Who you report to (and it is more than the regulator)

A SUSAR report fans out, and the recipients are where the EU and US diverge on detail. Under EU rules, SUSARs are reported to the national competent authority of the Member State concerned, and the sponsor’s responsibilities entail reporting SUSARs to the competent authority directly or through the EudraVigilance Clinical Trials Module (EU CT-3, sponsor responsibilities). The same EU obligation runs to the ethics committee, and the sponsor must also inform all investigators. In the US, the channel is the FDA IND safety report, with the sponsor notifying participating investigators and the reviewing IRB.

ICH E6(R3) sits above both and states the principle for the investigator-and-IRB leg: the reporting of SUSARs to investigators and IRBs/IECs should reflect the urgency of action required and be performed in accordance with applicable regulatory requirements (ICH E6(R3) §3.13.1). The point of all this fan-out is protective: regulators assess whether the product poses an unknown risk, ethics committees stay aware of what is happening to participants in their jurisdiction, and investigators get the safety signal they need to protect the people in front of them.

The minimum criteria: when a case becomes reportable

A SUSAR clock cannot start on a rumor. ICH E2A sets a floor of information a case must reach before it is a reportable case at all. For regulatory purposes, initial reports should be submitted within the prescribed time as long as the following minimum criteria are met: an identifiable patient, a suspect medicinal product, an identifiable reporting source, and an event or outcome that can be identified as serious and unexpected, and for which, in clinical investigation cases, there is a reasonable suspected causal relationship (ICH E2A, minimum criteria). Until those four elements exist, you do not yet have a SUSAR; you have a fragment to chase down.

This matters operationally because the reporting clock is measured from the sponsor’s first knowledge that the case meets those minimum criteria, not from the first vague mention of an event. Two practical consequences follow. First, follow-up is part of the obligation: when an incomplete report arrives, the sponsor is expected to actively seek the missing elements rather than wait. Second, you cannot game the clock by deliberately staying ignorant. Once the minimum criteria are in hand, the 7- or 15-day window is running, and “we hadn’t finished investigating” is not a defense for a late expedited report.

It helps to remember what the whole exercise is for. ICH E2A states that the purpose of expedited reporting is to make regulators, investigators, and other appropriate people aware of new, important information on serious reactions (ICH E2A, expectedness). That framing resolves a lot of edge cases. The question is never “can we technically avoid reporting this,” it is “would a regulator or an investigator need to know this now to protect participants.” A case that clears the minimum criteria and carries genuinely new safety information is exactly what the system exists to surface quickly, and that is the spirit in which the clocks and the criteria should be read.

Where teams get it wrong

• Reporting every SAE as a SUSAR. All SUSARs are SAEs, but the SUSAR filter also requires unexpected and suspected. Expected serious reactions go to periodic reporting.
• Treating expectedness as opinion. It is a comparison against the RSI version in force when the event occurred. Use the wrong RSI version and you mis-sort the case.
• Forgetting the EU 8-day follow-up. A 7-day initial report on a fatal or life-threatening SUSAR carries an additional 8-day follow-up obligation.
• Reporting only to the regulator. The ethics committee and the investigators are recipients too, not afterthoughts.
• Starting the clock at the wrong moment. The window runs from first knowledge that the minimum criteria are met, not from the first vague mention. Stalling on follow-up to delay the start is not a defense; the obligation includes actively chasing the missing elements.
• Letting an RSI update slip. When the RSI changes, the set of reportable SUSARs changes. The safety-reporting process has to track RSI versions.

A SUSAR programme that works is really a precise sorting machine: take each serious event, test causality and expectedness against the right RSI, and if both hold, run the case to the right recipients on the 7- or 15-day clock. The errors that draw findings are almost always a fuzzy filter or a missed recipient.

Sources

• ICH E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
• FDA, Safety Reporting Requirements for INDs and BA/BE Studies (21 CFR 312.32 guidance), 2012
• EU CT-3, Detailed guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials (2011)
• ICH E6(R3) Good Clinical Practice, version R3