1. Definitions

1.1 Adverse event (AE)

An AE is any untoward medical occurrence in a patient, consumer or a clinical investigation subject administered a medicine, which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (for example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicine, whether or not considered related to this medicine.

1.2 Adverse reaction (AR)

ARs concern noxious and unintended responses to a medicine.

This includes ARs that arise from:

• the use of a medicine within the terms of the marketing authorisation;
• the use outside the terms of the marketing authorisation, including overdose, abuse, off-label use, misuse, and medication errors; or
• occupational exposure.

The phrase 'responses to a medicine' means that a causal relationship between a medicine and an AE is at least a reasonable possibility.

A reaction, in contrast to an event, is characterised by the fact that a causal relationship between the medicine and the occurrence is suspected. For regulatory reporting purposes, if an event is spontaneously reported, even if the causal relationship is unknown or unstated, it meets the definition of an AR.

1.3 Serious adverse reactions

A serious AR is any untoward medical occurrence that at any dose:

• results in death;
• is life-threatening
• (Note: The term 'life-threatening' in the definition of 'serious' refers to an event/reaction in which the patient was at risk of death at the time of the event/reaction; it does not refer to an event/ reaction which hypothetically might have caused death if it were more severe);
• requires inpatient hospitalisation or results in prolongation of existing hospitalisation;
• results in persistent or significant disability/incapacity;
• is a congenital anomaly/birth defect; or
• is a medically important event or reaction.

Medical and scientific judgment should be exercised in deciding whether other situations should be considered serious such as important medical events that might not be immediately life-threatening or result in death or hospitalisation but might jeopardise the patient or might require intervention to prevent one of the other outcomes listed in the definition above. These should also be considered serious. Examples of such events include intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation, or development of drug dependency or drug abuse.

For reporting purposes, any transmission via a medicine of an infectious agent is also considered a serious AR and therefore must be reported in accordance with reporting timeframes for serious ARs.

Any organism, virus or infectious particle (e.g., prion protein transmitting Transmissible Spongiform Encephalopathy), pathogenic or non-pathogenic, is considered an infectious agent.

A transmission of an infectious agent may be suspected from clinical signs or symptoms, or laboratory findings indicating an infection in a patient exposed to a medicine. Emphasis should be on the detection of infections/infectious agents known to be potentially transmitted via a medicine, but the occurrence of unknown agents should also always be considered.

In the context of evaluating a suspected transmission of an infectious agent via a medicine, care should be taken to discriminate, whenever possible, between the cause (e.g., injection/ administration) and the source (e.g., contamination) of the infection and the clinical conditions of the patient at the time of the infection (immuno-suppressed /vaccinee).

If the infectious agent is specified, the MedDRA lowest level term code corresponding to the infectious agent should also be included in the report.

Confirmation of contamination (including inadequate inactivation/attenuation of infectious agents as active substances) of the concerned medicine increases the evidence for transmission of an infectious agent and may therefore be suggestive of a quality defect for which the procedures detailed in section 2.5.6 should also be applied.

1.4 Non-serious adverse reactions

All ARs that do not meet the definition of a serious AR are considered non-serious ARs.

1.5 Spontaneous reports

A spontaneous report is an unsolicited communication by a health professional or consumer to a company, regulatory authority or other organisation (e.g. WHO, Poisons Information Centre) that describes one or more suspected ARs in a patient who was given one or more medicine(s) and that does not derive from a study or any organised data collection system where AE reporting is actively sought. Stimulated reporting can occur in certain situations, such as notification by a 'Dear Healthcare Professional' letter, publication in the press, questioning of healthcare professionals by company representatives, communication from patients' organisations to their members, or class action lawsuits. These reports should be considered spontaneous.

1.6 Healthcare professional

A healthcare professional is a medically qualified person such as a medical doctor, dentist, pharmacist, or nurse.

1.7 Consumer

A consumer is a person who is not a healthcare professional such as a patient, lawyer, friend, or relative of a patient.

1.8 Post-registration study

A post-registration study is any study carried out in accordance with the conditions of registration or under normal conditions of use. This includes studies that may have commenced prior to registration that are ongoing after the product has been registered. In relation to AR reporting and PSUR requirements, reference to a post-registration study means any post-registration study (carried out in accordance with the conditions of registration or under normal conditions of use) of which the sponsor is aware.

1.9 Overdose

This refers to the administration of a quantity of a medicine given per administration or cumulatively, which is above the maximum recommended dose according to the authorised PI or the directions for use on the medicine label.

1.10 Off-label use

This relates to situations where the medicine is intentionally used for a medical purpose not in accordance with the authorised PI or the directions for use on the medicine label.

1.11 Misuse

This refers to situations where the medicine is intentionally and inappropriately used not in accordance with the authorised PI or the directions for use on the medicine label.

1.12 Abuse

This corresponds to the persistent or sporadic, intentional excessive use of a medicine, which is accompanied by harmful physical or psychological effects.

1.13 Medication error

This refers to any unintentional error in the prescribing, dispensing, or administration of a medicine while in the control of the healthcare professional, patient or consumer.

1.14 Occupational exposure

This refers to exposure to a medicine as a result of one's professional or non-professional occupation.

1.15 Primary source

The primary source of the information on a suspected AR(s) is the person who reports the facts to the sponsor. Several primary sources, such as healthcare professionals and/or a consumer, may provide information on the same case. In this situation, the details of all primary sources, including the qualifications, should be provided in the case report.

2. Guidance on data management

Sponsors must be familiar with and discharge their obligations in relation to the collection, use and disclosure of personal information in accordance with the National Privacy Principles based on the Privacy Act 1988. These obligations are set out in the Guidelines on Privacy in the Private Health Sector, Office of the Federal Privacy Commissioner, November 2001⁶⁵. This is particularly important where the consumer is the reporter. In these cases the TGA's requirement for sponsors to provide information on an identifiable reporter does not override these privacy principles and explicit consent to the disclosure of the consumer's identity to the TGA must be sought⁶⁶.

Electronic data and paper reports of suspected ARs should be stored and treated in the same way as other medical records with appropriate respect for confidentiality regarding patients' and reporters' identifiability and in accordance with data privacy laws.

In order to ensure pharmacovigilance data security and confidentiality, strict access controls to authorised personnel only should be applied to documents and to databases. This security extends to the complete data path. In this aspect, procedures should be implemented to ensure security and non-corruption of data during data transfer. When transfer of pharmacovigilance data occurs within an organisation or between organisations having concluded contractual agreements, the mechanism should be such that there is confidence that all notifications are received. A confirmation and/or reconciliation process should therefore be undertaken.

Correct data entry, including the appropriate use of terminologies, should be verified by quality assurance auditing, either systematically or by regular random evaluation. Data entry staff should be instructed in the use of the terminologies, and their proficiency confirmed.

Electronic data storage should allow traceability (an audit trail) of all data entered or modified, including dates and sources of received data, as well as dates and destinations of transmitted data.

A procedure should be in place to account for identification and management of duplicate cases at data entry and during the generation of aggregated reports.

Conformity of stored data with initial and follow-up reports should be verified by quality control procedures, which permit for the validation against the original data or images thereof. In this aspect, the source data (e.g., letters, emails, records of telephone calls that include details of an event) or an image of the source data should be easily accessible.

Footnotes

65. The Guidelines on Privacy in the Private Health Sector, Office of the Federal Privacy Commissioner, November 2001 can be viewed online at Privacy in the Private Health Sector (November 2001).
66. Section 2.6 includes further information about consumer reports.