This section deals only with investigation and reporting of adverse drug reactions and adverse drug events. Furthermore, this section seeks to clarify the pharmacovigilance reporting responsibilities of each party involved in delivering the homecare service, with the overall aim of ensuring compliance with good pharmacovigilance practice, whilst avoiding duplication of reports11.
Note: Throughout this section 9.3 the term manufacturer should be read as the manufacturer or marketing authorisation holder (MAH) if different.
Definiton: Adverse drug reaction (ADR)
Adverse Drug Reaction is defined in DIR 2010/84/EU as a response to a medicinal product that is noxious and unintended (side effect)” which results not only from the authorised use of a medicinal product at normal doses, but also from medication errors and uses outside the terms of the marketing authorisation, including the misuse and abuse of the medicinal product and occupational exposure.
Definition: Serious adverse drug reaction
The serious adverse drug reaction is defined in DIR 2001/83/EC Art 1(12) as an adverse reaction which results in death, is life-threatening, requires in-patient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect or any suspected transmission via a medicinal product of an infectious agent is also considered a serious adverse reaction.
Definition: Spontaneous adverse drug reaction report
A spontaneous adverse drug reaction report is defined in GVP VI as an unsolicited communication by a healthcare professional, or consumer to a competent authority, marketing authorisation holder or other organisation (e.g. Regional Pharmacovigilance Centre , Poison Control Centre) that describes one or more suspected adverse reactions in a patient who was given one or more medicinal products and that does not derive from a study or any organised data collection systems where adverse events reporting is actively sought, as defined in VI.B.1.2.
Stimulated reporting that occurs consequent to a “Direct Healthcare Professional Communication”, publication in the press, questioning of healthcare professionals by company representatives, communication from patients’ organisations to their members, or class action lawsuits should be considered spontaneous reports.
Definition: Solicited adverse drug reaction report
GVP VI VI.B.1.2 refers to solicited ADR reports as defined in ICH-E2D. Solicited reports of suspected adverse reactions are those derived from manufacturer’s organised data collection systems, which include clinical trials, non-interventional studies, registries, post-approval named patient use programmes, other patient support and disease management programmes, surveys of patients or healthcare providers, compassionate use or name patient use, or information gathering on efficacy or patient compliance.
Solicited ADR reports to the regulator are made by the manufacturer (or marketing authorisation holder if different) and are classified as study reports.
Reports of suspected adverse reactions obtained from any of the data collection systems listed above report should not be considered spontaneous. This is with the exception of:
- suspected adverse drug reactions in relation to those adverse drug events for which the protocol of non-interventional post-authorisation studies provides differently and does not require their systematic collection (see VI.C.1.2.1.),
- suspected adverse drug reactions originating from compassionate use or named patient use conducted in European Member States where the active collection of adverse events occurring in these programmes is not required (see VI.C.1.2.2.).
Definition: Validated adverse drug reaction report
To be valid for submission to the MHRA, an adverse drug reaction report (also known as Individual Case Safety Report or Yellow Card Report) requires the following elements:
- Anonymised Patient reference e.g. initials and gender
- Reporter identifier e.g. name/staff type/homecare provider name
- Name and details of the medicine
- Details of the adverse drug reaction
The report should also confirm:
- that the medicine was taken
- that the patient was harmed
There is reasonable suspicion or knowledge that the harm was caused by the medicine taken, usually conformed by the person first identifying or reporting the adverse drug reaction. GVP VI refers to WHO guidance on assessment of causality. It is important to note that the fact that a spontaneous ADR report is submitted to the regulator is taken to imply that the reporter has reasonable suspicion or knowledge of causality. 12
Definition: Adverse drug event (ADE)
For the purposes of this guideline, the definition of an adverse drug event is
- any untoward medical occurrence in a homecare patient administered a medicinal product and which does not necessarily have a causal relationship with the medicinal product or is related to one or more omitted doses or otherwise does not meeting the definition of a validated adverse drug reaction
- overdose, abuse, off-label use, misuse, medication error or occupational exposure with no associated adverse reaction
- pregnancy related exposure where the embryo or foetus may have been exposed to medicinal products (either through maternal exposure or transmission of a medicinal product via semen following paternal exposure) or infant exposure during breastfeeding with no associated adverse reaction.
An adverse drug reaction, by definition, results in actual patient harm so must always also be treated as a patient safety incident as described in section 9.1. Adverse drug events of clinical significance should also be reported immediately to the clinical team and treated as patient safety incidents e.g. patient harm or other clinical concerns which are not caused by the medicine; patient harm arising from omitted doses due to failed medicine delivery or medicine shortage.
The reporting of adverse drug events, which do not meet the criteria of a patient safety incident, is not so clear-cut (see section 9.3.6). Where it is suspected that an adverse drug event may meet the requirements of a valid ADR it should be reported as a possible ADR that is then subject to further validation by the manufacturer.
Whilst this section is specific to medicine and drug related incidents, it is good practice to have a similar reporting process for medical devices to capture device related events which do not fulfil the criteria for Faulty Medical Device reporting (see section 9.4), especially where the medical device manufacturer funds the homecare service.