Adverse Events: Recognizing and Recording Them

Part of Clinical Research Coordinator (CRC) Training: Participant Safety.

About 6 minutes. Free, in your language, no account needed.

Why this matters

Safety reporting is the part of your job where a mistake can hurt somebody who is not your participant. Harms are detected by pooling events across hundreds of sites. An event your site never recorded is an event that cannot contribute to that picture.

The rule is simple to state and hard to apply under time pressure: if in doubt, record it and let the investigator decide.

What an adverse event is

An adverse event is any untoward medical occurrence in a participant who has been given a medicinal product, whether or not it is related to that product.

Read that definition twice, because two parts of it are counter-intuitive.

It does not have to be caused by the treatment. A participant who breaks an ankle falling off a bicycle has had an adverse event. Relatedness is assessed separately, and by the investigator.

It does not have to be dramatic. Headache, nausea, tiredness, a rash, an abnormal laboratory result that the investigator considers clinically significant — all are adverse events.

An adverse reaction is an adverse event for which there is a reasonable possibility that the product caused it. That is a judgment, and it belongs to the investigator.

Two independent judgments

New coordinators confuse these constantly. They are separate and they do not affect each other.

Severity is how bad the event is: commonly mild, moderate or severe, or graded on a scale the protocol specifies.

Seriousness is a regulatory classification with a defined list of criteria. An event is serious if it:

• results in death;
• is life-threatening;
• requires hospitalization or prolongs an existing hospitalization;
• results in persistent or significant disability or incapacity;
• is a congenital anomaly or birth defect;
• or is another important medical event that, in medical judgment, may jeopardize the participant or require intervention to prevent one of the above.

A severe headache is not necessarily serious. A symptomless finding that leads to hospital admission is serious. Never use the two words interchangeably.

Finding events

Adverse events do not announce themselves. Find them systematically.

• Ask an open question first, at every visit: "Since we last saw you, have you had any change in your health?" Open questions before specific ones; leading with a symptom list produces reporting bias.
• Review the sources. Clinic notes, letters from other doctors, hospital discharge summaries, laboratory and imaging results, the participant's diary, and the medication list. A new medicine usually means a new problem.
• Follow up telephone calls and cancellations. A missed visit is sometimes a hospital admission.
• Know the protocol's collection period. When adverse event collection begins — often at consent or at first dose — and how long after the last dose it continues.

Recording an event

Record in source first, then in the CRF. Each event needs:

• A diagnosis if one exists, rather than a list of symptoms. "Community-acquired pneumonia" is better than "cough, fever, breathlessness". If there is no diagnosis, record the signs and symptoms as reported.
• The onset date, and the end date when it resolves.
• Severity, using the protocol's scale.
• Whether it meets any seriousness criterion.
• The investigator's causality assessment.
• Action taken with the investigational product: none, dose reduced, interrupted, or withdrawn.
• Treatment given for the event.
• The outcome: resolved, resolving, ongoing, resolved with sequelae, fatal.

One event per record. Do not merge two problems into one line because they happened together.

Do not use abbreviations the reader may not share, and do not write "as above".

The investigator's part

The investigator assesses causality and clinical significance. These are medical judgments and E6(R3) requires them of the investigator, not of the coordinator.

Your job is to make sure the assessment happens, is recorded, and is dated. Chasing the investigator for a causality assessment is a legitimate and important part of the role.

Ongoing events and follow-up

An event is not finished when the visit ends.

• Follow every event to its outcome, and record it.
• Update severity, seriousness and causality if new information changes them. An event that becomes serious later must be re-reported as serious.
• Keep supporting documents: discharge summaries, specialist letters, test results.
• Some events continue past the participant's last visit. The protocol says how long you must follow them.

In practice

At a routine VT-201 visit, Nadia asks her open question. The participant mentions, almost in passing, that she was in hospital overnight three weeks ago with dizziness, and that it was "nothing to do with the study".

Nadia does not accept that assessment, kindly or otherwise, because it is not the participant's to make. An overnight admission meets a seriousness criterion. She records the event, obtains the discharge summary with the participant's permission, and takes it to Dr. Osei the same day.

Dr. Osei assesses causality. He judges it possibly related, because dizziness on standing is consistent with blood pressure lowering. The event is reported to Vantis Pharma as a serious adverse event, dated from the day the site became aware.

The participant is surprised that her overnight stay mattered. Nadia explains that this is exactly the kind of thing the study exists to detect, and that reporting it does not mean she has to stop.

Participants routinely decide, on their own, that an event is not worth mentioning. Ask in a way that makes it easy for them to be wrong about that.

Key takeaways

• An adverse event is any untoward medical occurrence in a participant given a medicinal product, whether or not it is related to that product.
• Severity and seriousness are different judgments: severity is how bad the event is, seriousness is a defined regulatory classification including death, life-threatening events, hospitalization, disability and congenital anomaly.
• Ask an open question about health changes before any specific symptom question, and review notes, letters, results, diaries and medication lists systematically.
• Record a diagnosis where one exists, with onset and end dates, severity, seriousness, causality, action taken with the product, treatment and outcome, one event per record.
• Causality and clinical significance are the investigator's medical judgments, and the coordinator's job is to ensure they are made, recorded and dated.