Standard Operating Procedure
Spontaneous Reporting of Adverse Drug Reactions
(This SOP consists of X pages (including this cover sheet and addendum).
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Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
Table of Contents
Standard Operating Procedure ..................................................................................................... 1
1
Introduction ......................................................................................................................... 3
2
Purpose ................................................................................................................................ 3
3
Scope .................................................................................................................................... 4
4
Responsibilities .................................................................................................................... 4
5
Reporting Procedure ............................................................................................................ 4
5.1 Reporting : Reporting Form .......................................................................................... 4
5.2 Where to Report ............................................................................................................ 5
5.3 What to Report: Essential data elements ...................................................................... 6
5.4 Advice to reporters ........................................................................................................ 8
5.5 Report follow-up ........................................................................................................... 9
5.6 When to report .............................................................................................................. 9
5.7 Who should report......................................................................................................... 9
5.8 Reporters feedback...................................................................................................... 10
5.9 Alternative Reporting methods ................................................................................... 10
5.10 Data Entry and Data Management .......................................................................... 11
6.0 Definitions ......................................................................................................................... 12
6.1 Pharmacovigilance ...................................................................................................... 12
6.2 Pharmacovigilance Centre .......................................................................................... 12
6.3 Signal .......................................................................................................................... 12
6.4 Adverse Drug Reaction ............................................................................................... 13
6.5 Serious adverse reaction ............................................................................................. 13
6.6 Adverse Event ............................................................................................................. 13
6.7 Healthcare Proffessional ............................................................................................. 13
6.8 References ................................................................................................................... 13
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
1 Introduction
Pharmacovigilance using a spontaneous reporting system is designed to detect Adverse Drug
Reactions (ADRs) occurring in clinical practice, particularly those not previously observed in
preclinical or clinical studies, to improve understanding of the potential risks, including
reactions resulting from drug interactions or drug effects in particular populations, and to
help provide a basis for effective patient management, drug regulation, education and
consequent changes in practices by prescribers and consumers.
Spontaneous reporting is dependent on the potential reporter being educated
and
motivated to record and submit her/his observations . This is the most common form of pharmacovigilance. It is sometimes referred to as “voluntary” reporting. In some countries this
form of reporting is mandatory. Clinicians, pharmacists and community members should be
trained on how, when and what to report. Targeted (stimulated, facilitated, enhanced)
spontaneous reporting provides reporters with targets (drugs and ADRs of special interest),
tools (standardized data collection forms and facilitation of transmission to the
pharmacovigilance centers) and training as to what methods to use to overcome the known
limitations of spontaneous reporting especially under-reporting. While cohort event
monitoring may be "gold standard" it may not always be feasible or sustainable in resource
limited settings. In such situations, spontaneous reporting may be an acceptable alternative.
Spontaneous reporting also provides a long-term view of medicines.
By definition, a spontaneous report is an unsolicited communication by health care professionals or consumers that describes one or more ADRs in a patient who was given one or
more medicinal products and that does not derive from a study or any organized data
collection scheme.
2 Purpose
The purpose of this standard operating procedure is to outline a step by step approach for
employing the spontaneous reporting of adverse drug reactions in monitoring medicines
safety for use at National Pharmacovigilance Centers. It is applicable to all medicines.
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
3 Scope
This document is relevant to personnel intending to establish and/ or running a
pharmacovigilance centre (PvC).
4 Responsibilities
Identify the personnel that have a primary role in the SOP and describe how their
responsibilities relate to this SOP. If necessary, include contact information.
5 Reporting Procedure
5.1
Reporting : Reporting Form
5.1.1 Each country with a pharmacovigilance centre needs to have at least one standard
reporting form for documenting ADRs.
5.1.2 Pharmacovigilance centers will have, or should develop their own standard reporting
form(s)
5.1.3 The reporting form needs to be available in the local language(s)
5.1.4 The reporting form should have features relating it to the responsible authority e.g. a
logo, the address and contact details of the issuing institution.
5.1.5 The reporting form should be simple and easy to complete
5.1.6 The reporting form should not request too much information, particularly information
that is difficult to find and record, or information that is unlikely to be used.
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
5.1.7 The reporting form should be widely distributed to all health professionals including
those who are working privately. Difficulty in finding a reporting form is a common
barrier to reporting.
5.1.8 The forms should be printed on a single sheet of paper and be easily folded and
sealed.
5.1.9 To facilitate postage, the return address should be printed on the outside, preferably
with postage pre-paid.
5.1.10 It is desirable to have only one type of reporting form available in the country for use
for all medicines.
5.1.11 The reporting form should have sufficient space in which to describe the suspected
reaction(s).
The form should carry a statement reassuring confidentiality of information given
5.2
Where to Report
5.2.1 Reports should be sent to the designated PvC (national,regional, or zonal).
5.2.2 If it is not practical to send the forms directly to the centre, it may be necessary to
arrange points of collection at other sites such as specific hospitals or clinics.
5.2.3 The reports should be stored securely to maintain privacy.
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
5.3
What to Report: Essential data elements
5.3.1 Patient details
5.3.1.1 Health number (depending on availability): this may be a national identifier
(preferred), hospital, clinic, or programme number.
5.3.1.2 Name: full name or initials depending on the requirements of local privacy legislation.
Patient identification is important for follow-up purposes and avoidance of
duplication.
5.3.1.3 Address: to allow for follow-up and accurate identification. This may take various
forms depending on the location.
5.3.1.4 Sex
5.3.1.5 Date of birth (preferred) or age (add ‘est’ if age is estimated).
5.3.1.6 Weight and height
Pregnancy status
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
5.3.2 Patient medical history of significance
5.3.3 Details of medicines:
5.3.3.1 Name(s): (this may be brand or generic) and formulation (e.g. tablets, syrup,
injection). Reporting the brand name gives more specific information and is
recommended.
5.3.3.2 Mode of administration (e.g. oral, rectal, injection).
5.3.3.3 Indication(s) for use.
5.3.3.4 Dose: Size of each dose and dosage interval is preferred. If not availablerecording the
total daily dose is appropriate.
5.3.3.5 Date of commencement
5.3.3.6 Date of withdrawal.
5.3.3.7 Duration of use, if dates of commencement and withdrawal are not available.
5.3.3.8 All medicines being taken at the time of the event should be listed. Each suspect
medicine can be indicated by an asterisk or any other appropriate means.
5.3.4 Reaction details
5.3.4.1 Date of onset.
5.3.4.2 Reporters should be asked to give a brief clinical description. They should not be
asked to give the official pharmacovigilance reaction term.
5.3.4.3 Laboratory or other test results if available, together with units.
5.3.4.4 Seriousness and outcome of event: resolved, resolving, no change, disabling,
worsening, requiring hospitalization or treatment , life-threatening, fatal (with date),
congenital anomaly.
5.3.4.5 Effect of drug withdrawal and re-exposure (if relevant)re-challenge (if any).
Previous medical history e.g. allergy or experience with same or similar medicine
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
5.3.5 Reporter details
5.3.5.1 Name.
5.3.5.2 Contact details.
5.3.5.3 Status: e.g. physician, nurse, patient.
5.3.5.4 Date and place of report
5.4
Advice to reporters
5.4.1 Report any suspected adverse reaction of concern.
5.4.2 Report all suspected serious reactions. A serious reaction:
 results in death;
 is life-threatening;
 requires hospitalization or prolongation of hospitalization;
 results in persistent disability;
 is a congenital anomaly.
5.4.3 Report persistent adverse reactions that could threaten adherence.
5.4.4 Reporters should be advised that they need not to be sure that the medicine caused
the event.
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
5.5
Report follow-up
5.5.1 All reports of serious events should be followed up if details are incomplete. This may
require the involvement of health professionals trained and appointed for this type of
work.
5.5.2 Occasionally follow-up information is required to fully assess reports of non-serious
events. Follow-up requests should be kept to a minimum because they can act as a
deterrent to further reporting. Examples might be:
 a request for essential missing details;
 information on the final outcome;
 the result of re-exposure;
 the results of laboratory or other tests;
 post-mortem results from the health facility where autopsy is undertaken.
5.6
When to report
5.6.1 A report should be completed and submitted as soon as possible after the reaction
happened.
5.6.2 It is better to advice reporters not to wait until final results and information such as
hospital letters are received, because the report may be forgotten. These additional
details can be sent to the PvC at a later date
5.7
Who should report
The following is a list of potential reporters. They may work in the public or private health
sectors.
 Physicians and dentists.
 Pharmacists.
 Nurses.
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
 Other (literate) health and community workers should be encouraged to detect and
report, preferably to the clinician who prescribed the treatment, or directly to the
PvC.
 Public health programmes.
 Pharmaceutical companies.
 Patients or patient representatives.
5.8
Reporters feedback
5.8.1 Anyone who sends in a report should receive an acknowledgement letter and further
reporting forms.
5.8.2
The letter should, if possible,provide some brief information about the reaction
reported and measures that will be taken to potentially prevent reoccurrence in that
particular patient or other patients
5.9
Alternative Reporting methods
5.9.1 Telephone. The person receiving the report should have a reporting form to record the
details and make sure that essential data are not missing.
5.9.2 Fax. Sending reports by fax is equivalent to posting the report, but faster. A fax
machine is a very important asset for national PvC and its major sentinel sites.
5.9.3 E-mail. A written case-report submitted by e-mail may be acceptable. Further details
can be obtained by follow-up. Reporting forms can be sent to reporters as e-mail
attachments and they can be e-mailed, faxed or posted to the PvC when completed.
5.9.4 The Internet. An Internet site is a valuable asset for a PvC and a reporting form could
be made available for downloading or for completion online (entering data through
web-based data entry) if the site is secure
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
5.10
Data Entry and Data Management
5.10.1 All PvC should have a complete data/ case management system e.g. VigiFlow™ (see
below) for managing data within the country
5.10.2 All PvC should have trained data entry personnel
5.10.3 Details of reports should be sent for international analysis to the WHO Collaborating
Centre for International Drug Monitoring (UMC) at least monthly.
5.10.4 The PvC should decide which data can be transferred to WHO database (Vigibase) and
when it will be transferred. The use of VigiFlow (described below) simplifies this
procedure.
5.10.4.1 VigiFlow
 It is web-based and requires no local support or maintenance.
 VigiFlow provides an online database unique to the national PvC.
 Data entered are confidential to, and are owned by the country that enters them.
 VigiFlow is compatible with the international standard for exchange of individual case
safety information (ICH-E2b) and provides for standardized entry of data from reports.
 It has built-in error avoidance features.
 A search and statistics module provides summary tabulations, line listings and a range
of standard statistical analyses
 National data can be accessed and used by the national and local PvC.
 The data can be exported to local country databases or to marketing authorization
holders (e.g. in pdf or Excel format) for ad hoc searches and to meet local analytical
requirements.
 It provides live access to up-to-date terminologies: WHO Drug Dictionary (DD) and
MedDRA and WHO Adverse Reactions Terminology (WHO-ART).
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
 VigiFlow is maintained, continuously developed and provided to national PvCs by the
Uppsala Monitoring Centre
6 Definitions
6.1
Pharmacovigilance
Pharmacovigilance has been defined as: The science and activities relating to the detection,
assessment, understanding and prevention of adverse effects or any other drug-related
problem (WHO).
6.2
Pharmacovigilance Centre
The Pharmacovigilance Centre (PvC) of an individual country is responsible for meeting the
requirements for pharmacovigilance of all medicines and is a centre of expertise for the art
and science of monitoring and analysis, and use of the analysed information for the benefit of
patients. National and any regional Pharmacovigilance Centers should be set up with the
approval of the authority responsible for the regulation of medicines (“regulatory authority”).
The centre may function within the regulatory authority, a hospital, an academic institution
or as an independent facility such as a trust or foundation.
6.3
Signal
Reported information on a possible causal relationship between an adverse event and a drug,
the relationship being unknown or incompletely documented previously. Usually more than a
single report is required to generate a signal, depending upon the seriousness of the event
and the quality of the information. (WHO)
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
6.4
Adverse Drug Reaction
A response to a medicinal product which is noxious and unintended and which occurs at
doses normally used in man for the prophylaxis, diagnosis or therapy of disease or for the
restoration, correction or modification of physiological function. (WHO)
6.5
Serious adverse reaction
Any untoward medical occurrence that at any dose results in death, is life threatening,
requires or prolongs patient hospitalization, results in persistent disability/incapacity, or is a
congenital anomaly/birth defect (International Conference on Harmonization (ICH)). The term
Life-threatening” in the definition of “serious” refers to an event in which the patient was at
risk of death at the time of the event; it does not refer to an event, which hypothetically
might have caused death if it was more severe.
6.6
Adverse Event
Any untoward medical occurrence that may present during treatment with a pharmaceutical
product but which does not necessarily have a casual relationship with this treatment. (WHO)
6.7
Healthcare Professional
For the purposes of suspecting adverse reactions, healthcare professionals are defined as
medically qualified persons such as physicians, dentists, pharmacists and nurses.
6.8
References
List resources that may be useful when performing the procedure; for example, Admin
policies, Municipal Code, government standards and other SOPs.
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions
Standard Operating Procedure: Spontaneous Reporting of Adverse Drug Reactions