Pharmacovigilance Interview Questions

Please note, final edits are pending.

Pharmacovigilance/ Drug safety: As per WHO, Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.

ICH: The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)

PSUR: Periodic Safety Update Reports (PSUR)

SUSAR: Suspected Unexpected Serious Adverse Reactions (SUSAR).

ADR (Adverse Drug Reaction):

What is an adverse drug reaction?

• An adverse drug reaction (ADR) is an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use, which is suspected to be related to the drug.
• The reaction may be a known side effect of the drug or it may be new and previously unrecognised.

Is the reaction an ADR or an adverse event?

'Adverse reactions' and 'adverse events' are not always the same.

• An adverse event is any undesirable event experienced by a patient whilst taking a medicine, regardless of whether or not the medicine is suspected to be related to the event. An example of an adverse event is a patient being hit by a car while on a specific medication, whereas
• An adverse drug reaction is any undesirable experience that has happened to the patient while taking a drug that is suspected to be caused by the drug or drugs. An example of an ADR could be a patient experiencing anaphylaxis shortly after taking the drug.

The Yellow Card Scheme relies on reporting of suspected adverse drug reactions where there is a suspicion that there is a causal relationship between the medicinal product taken and the suspected reaction experienced.

Classification of adverse drug reactions

Adverse drug reactions are frequently classified as ‘type A’ and ‘type B’ reactions. An extended version of this classification system is shown here:

Type A Reactions
Type A (augmented) reactions result from an exaggeration of a drug’s normal pharmacological actions when given at the usual therapeutic dose and are normally dose-dependent.

• Examples include respiratory depression with opioids or bleeding with warfarin

Type A reactions also include those that are not directly related to the desired pharmacological action of the drug (e.g. dry mouth that is associated with tricyclic antidepressants).

Type B Reactions
Type B (bizarre) reactions are novel responses that are not expected from the known pharmacological actions of the drug. These are less common, and so may only be discovered for the first time after a drug has already been made available for general use

• Examples include anaphylaxis with penicillin or skin rashes with antibiotics

Type C Reactions 
Type C, or ‘continuing’ reactions, persist for a relatively long time.

• An example is osteonecrosis of the jaw with bisphosphonates

Type D Reactions 
Type D, or ‘delayed’ reactions, become apparent some time after the use of a medicine. The timing of these may make them more difficult to detect.

• An example is leucopoenia, which can occur up to six weeks after a dose of lomustine

Type E Reactions 
Type E, or ‘end-of-use’ reactions, are associated with the withdrawal of a medicine.

• An example is insomnia, anxiety and perceptual disturbances following the withdrawal of benzodiazepines

Other classification schemes have also been proposed, such as ‘DoTS’, which takes into account Dose-related, Time-related and Susceptibility factors.

How to identify adverse drug reactions

Patients may tell you about symptoms they have experienced since taking a new medicine, and it is important to listen to the patient’s own concerns regarding their drug therapy. However, as some adverse reactions may not be apparent to the patient, you will need to be alert to the possible occurrence of ADRs.

Your own observations and initiative will be vital in this respect, in linking a sign or symptom to either current or previous therapy. (Remember these can include over-the-counter (OTC) drugs and unlicensed herbal remedies).

Other things to be alert for include:

• Abnormal clinical measurements (e.g. temperature, pulse, blood pressure, blood glucose, body weight) while on drug therapy
• Abnormal biochemical or haematological laboratory results while on drug therapy. For example, plasma drug concentrations or liver biopsy where drug-induced hepatitis is suspected
• If new drug therapy is started which may be used to treat the symptoms of an ADR
• Listening to the patient’s own concerns regarding drug therapy.

The burden of ADRs

Adverse drug reactions are frequently serious enough to result in admission to hospital. It is well recognised that adverse drug reactions place a significant burden on the health service

Studies performed in an attempt to quantify this have shown adverse drug reactions account for 1 in 16 hospital admissions, and for 4% of hospital bed capacity.

ADRs themselves are also thought to occur in 10-20% of hospital in-patients, and one study found that over 2% of patients admitted with an adverse drug reaction died, approximately 0.15% of all patients admitted.

It is clear that adverse drug reactions adversely affect patients’ quality of life and can also cause patients to lose confidence in the healthcare system. There is a significant impact through increase costs of patient care and the potential to lengthen hospital stays. Adverse drug reactions may also mimic disease, resulting in unnecessary investigations and delays in treatment.

Adverse Drug Event (ADE):
An adverse event (i.e., injury resulting from medical care) involving medication use.

Examples:

• anaphylaxis to penicillin
• major hemorrhage from heparin
• aminoglycoside-induced renal failure
• agranulocytosis from chloramphenicol

As with the more general term adverse event, the occurrence of an ADE does not necessarily indicate an error or poor quality of care. ADEs that involve an element of error (either of omission or commission) are often referred to as preventable ADEs. Medication errors that reached the patient but by good fortune did not cause any harm are often called potential ADEs. For instance, a serious allergic reaction to penicillin in a patient with no prior such history is an ADE, but so is the same reaction in a patient who has a known allergy history but receives penicillin due to a prescribing oversight. The former occurrence would count as an adverse drug reaction or non-preventable ADE, while the latter would represent a preventable ADE. If a patient with a documented serious penicillin allergy received a penicillin-like antibiotic but happened not to react to it, this event would be characterized as a potential ADE.

An ameliorable ADE is one in which the patient experienced harm from a medication that, while not completely preventable, could have been mitigated. For instance, a patient taking a cholesterol-lowering agent (statin) may develop muscle pains and eventually progress to a more serious condition called rhabdomyolysis. Failure to periodically check a blood test that assesses muscle damage or failure to recognize this possible diagnosis in a patient taking statins who subsequently develops rhabdomyolysis would make this event an ameliorable ADE: harm from medical care that could have been lessened with earlier, appropriate management. Again, the initial development of some problem was not preventable, but the eventual harm that occurred need not have been so severe, hence the term ameliorable ADE.

Please note, final edits are pending.