Active Drug Safety Monitoring Activities

Severity rating scale for adverse events 

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Active drug safety monitoring (aDSM) consists of the following 3 core activities:

1. Patients targeted for aDSM should receive active and systematic clinical and laboratory assessment during RR-TB treatment to detect drug toxicity and adverse events.
2. All adverse events detected should be managed in a timely fashion to deliver the best possible patient care.
3. All severe (Grade 3 and above) adverse events and serious adverse events (SAEs) should be systematically collected in patient files and entered on EDRWeb - these data will be reported to the national pharmacovigilance centre (NPC). The NPC collects this type of data from the entire country and uses it to characterize the types of adverse events seen most commonly, assess the safety of the RR-TB treatment and inform future policy on the use of these medicines.
4. All adverse events that lead to interruption of a drug or the entire treatment regimen must be recorded in the folder and in the EDRWeb regardless of grading.
5. Sentinel sites need to record all adverse events (Grade 1 to 5) in both the patient’s folders and the EDRWeb.

For standardized data to be collected from a wide range of providers, scales have been developed to determine the severity of common adverse events. These scales tend to use a rating system from 1 to 5, with 1 being a mild side effect, 2 being a moderate side effect, 3 being a severe side effect, 4 being considered a life-threatening and 5 leading to death, side effect. Rating severity is often easier with laboratory values since discrete cut-off values can be used. See below for an example of a rating scale.

The term serious when applied to an adverse event in aDSM denotes a very specific category of side effect and it is different from a severe adverse event. A serious adverse event (SAE) is defined as an adverse event that results in any of the following:

• Hospitalization or prolongation of hospitalization to manage the adverse event;
• Permanent disability;
• Congenital abnormality;
• Life-threatening experience;
• Death.

Providers must document adverse events when they occur, and they should attempt to rate them using the severity scale below. An attempt should be made to determine causality where possible. This may be straightforward if the side effect is known to be associated with a particular medication (e.g. thrombocytopenia due to linezolid). In a multidrug regimen, it can be difficult to determine which drug is causing which side effect. Physicians, however, should follow best management practices, and the event's evolution over time could lead to a more precise causality assessment.

Severity rating scale for adverse events

Severity	Impact of symptoms
Mild (Grade 1)	Symptoms cause no or minimal interference with usual, age appropriate, social and functional activities (e.g. going to work, shopping, cooking, using transport, hobbies)
Moderate (Grade 2)	Symptoms cause greater than minimal interference with usual, age appropriate, social and functional activities (e.g. going to work, shopping, cooking, using transport, hobbies)
Severe (Grade 3)	Symptoms cause inability to perform usual, age appropriate, social and functional activities (e.g. going to work, shopping, cooking, using transport, hobbies)
Potentially life-threatening (Grade 4)	Symptoms cause inability to perform basic, age-appropriate, self-care functions (e.g. bathing, dressing, toileting, continence, feeding, movement); OR Medical or operative intervention required to prevent permanent impairment, persistent disability, or death
Death (Grade 5)	Death, regardless of cause or relationship to TB medications

Click here to access the pdf.

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National Department of Health Clinical Management of Rifampicin-Resistant Tuberculosis, September 2023

Active Drug Safety Monitoring Activities