A DSM Definitions

Clinical description

Pharmacovigilance: is one of the components of aDSM and is defined by WHO as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.” Adverse drug reaction (ADR): is a response to a TB medicine which is noxious and unintended, and which occurs at doses normally used in humans. This term is used to qualify adverse events that are thought to be related to a drug e.g. Peripheral neuropathy is an adverse reaction of linezolid.

Adverse event (AE): is any untoward medical occurrence that may present in a TB patient during treatment with a pharmaceutical product, but which does not necessarily have a causal relationship with this treatment.

Serious adverse event (SAE): is an AE that leads to: death or a life-threatening experience;

hospitalization or prolongation of hospitalization; persistent or significant disability; or a congenital anomaly. SAEs that do not immediately result in one of these outcomes but that require an intervention to prevent it from happening are included. SAEs may require a drastic intervention, such as termination of the drug suspected of having caused the event. All SAEs 124 National Tuberculosis Control Programme require completion of the SAEs Reporting Form and should be reported within 24 hours as part of the core package of aDSM.

Adverse event of special interest: is an AE documented to have occurred during clinical trials and for which the monitoring programme is specifically sensitized to report regardless of its seriousness, severity, or causal relationship to the TB treatment. Only provincial hospitals chosen to provide an intermediate or advanced package of aDSM (e.g. a selected sentinel site)

will include all AEs of special interest in their reporting.

Table 10.8-1 Adverse events of special interest

• Acute kidney injury (acute renal failure) • Ototoxicity
• Psychiatric disorders and central nervous system toxicity • Myelosuppression
• Optic nerve disorder (optic neuritis) or retinopathy • Peripheral neuropathy (paresthesia)
• Phospholipidosis • Hypokalemia,
• Prolonged QT interval • Pancreatitis
• Lactic acidosis
• Hepatitis
• Hypothyroidism

Adverse event leading to treatment discontinuation or change in drug dosage: is one that leads a clinician to stop, interrupt temporarily or change the dosage of one or more drugs, regardless of its seriousness, severity, or causal relationship to the TB treatment.

Adverse event of clinical significance: is an AE which is either (i) serious, (ii) of special interest, (iii) leads to a discontinuation or change in the treatment, or (iv) judged as otherwise clinically significant by the clinician. Only provincial hospitals providing the advanced package of aDSM (e.g. a selected sentinel site) will include all AEs of clinical significance in their reporting.

Medical errors: Unintended mistakes in the prescribing, dispensing or administration of a medicine that could cause harm to a patient (e.g. wrong drug prescribed, overdose) must be managed on a case by case basis. Medical errors (including overdoses) should be reported in expedited manner even if they did not lead to serious medical consequences.

Causality assessment: is the evaluation of the likelihood that a DR-TB drug was the causative agent of an observed adverse reaction. The formal causality assessment is performed by experts at the national Pharmacy and Poison Board.

Causal relationship: is a relationship between an exposure (A) and an event (B) in which (A)

precedes and causes B. This may refer to the causal association between an exposure to a TB medicine and the occurrence of an adverse reaction.

Signal: is reported information on a possible causal relationship between an adverse event and a DR-TB drug, the relationship being unknown or incompletely documented previously or representing a new aspect of a known association.