16. Seriousness assessment of adverse event reports

Correct seriousness assessment is critical in case processing as it impacts regulatory reporting and product safety. Below guidance must be followed while assessing seriousness criteria of events.

Regulatory Definition of a Serious Adverse Event:

Any untoward medical occurrence or effect that at any dose results in 

1. death, 
2. life-threatening, 
3. requires hospitali­sation or prolongation of existing hospitalisation, 
4. results in persistent or significant disability or incapacity, 
5. congenital anomaly or birth defect, 
6. any event that may not result in death/be life threatening/require hospitalisation may be considered a serious adverse drug experience when, based upon medical judgment, it may jeopardise the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Seriousness – Death: 

1. Death should be considered as seriousness criteria only if it is reported by reporter. 
2. The reporter must mention in the report that patient died while on/after receiving treatment medication. 
3. If reported event is completed suicide then it should be categorised under death.
4. If reported event is suicide then follow up request to be sent to confirm as attempted suicide or completed suicide. 

Seriousness – Life threatening: 

1. Life-threatening refers to a reaction in which the patient was at risk of death at the time of the reaction; it does not refer to a reaction that hypothetically might have caused death if more severe.
2. For example, if patient had cardiac arrest and taken to hospital then seriousness will be hospitalisation not life threatening. 
3. If patient was in coma or require ventilator support can be considered as life threatening conditions. 
4. Life threatening can be considered as seriousness if reporter clearly mentions in report that patient is in Life threatening condition.

Seriousness – Hospitalisation:

Hospitalisation considered as serious criteria if patient administered to hospital (with minimum 24 hrs stay) or caused prolongation of hospitalisation for any event. 

Below cannot be considered as hospitalisation: 

1. If hospitalisations described in the Protocol e.g., for drug administration or protocol required tests. 
2. If hospitalisations for social reasons in the absence of an AE e.g., subject with Alzheimer’s Disease admitted to hospital in order to give caregiver relief. 
3. Surgery/procedure planned prior to trial entry (record in CRF at screening visit) 
4. Accident and Emergency visit – subject treated and released 
5. Subject held 24 hrs for observation and not admitted 
6. Procedure performed in hospital on an out- patient basis (if stay <24 hrs) 
7. Treatment at centres not associated with a hospital, usually for minor surgical procedures, e.g., chiropody, laser eye surgery 

Seriousness – Disability:

Disability to be considered as seriousness criteria if:

1. Reported by reporter 

2. Loss of body part because of event

3. Injuries requiring major intervention, e.g.:

• Surgical intervention in the OR
• Burns needing debridement/skin grafts 

4. Loss, or substantial limitation of, bodily function lasting greater than 7 days, e.g., 

• Bodily functions related to: breathing; dressing/undressing; drinking; eating; eliminating waste products; getting into or out of bed, chair, etc; hearing; seeing; sitting; sleeping; or walking.

Seriousness – Congenital anomaly:

1. Congenital anomalies, also commonly referred to as birth defects, congenital disorders, congenital malformations, or congenital abnormalities, are conditions of prenatal origin that are present at birth, potentially impacting an infant’s health, development and/or survival. 
2. This seriousness criteria can be used only in pregnancy reports where parent exposed to medication while mother being pregnant and baby had birth defect because of medication.

Seriousness – Important medical event: 

Based upon medical judgment any event can be considered as serious adverse event 

1. If patient require medical or surgical intervention to prevent one of the outcomes listed in the definition (i.e, death/hospitalisation/life threatening etc…)

2. If the reported event present in Important medical event (IME) terms list which is prepared and maintained by EMA.

3. The events which meets criteria of grade 3 and above in Common Terminology Criteria for Adverse Events (CTCAE) list must be considered as serious.

Common Terminology Criteria for Adverse Events:

The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.

Grades: Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:

Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age- appropriate instrumental Activities of Daily Living.

Grade 3: Severe or medically significant but not immediately life-threatening; hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self care ADL.

Grade 4: Life-threatening consequences; urgent intervention indicated.

Grade 5: Death related to AE.