The information obtained during clinical trials of new drugs is by design insufficient to provide a comprehensive overview of its safety and effectiveness in routine clinical practice (limitations of pre-licensure clinical studies include short duration, small numbers of patients, exclusion of patients with other diseases, exclusion of pregnant women, infants and the elderly).The long-term safety of a medicine is thus only known when the drug is being used widely in a population and its safety is being monitoring by organized local, national and international efforts.
Many adverse drug reactions (ADRs) are preventable and a good knowledge of pharmacology, good prescribing practices and the provision of simple tools and facilities would reduce drug-related morbidity and mortality in humans. However, there are some ADRs which are unknown, unpredictable and not preventable though an understanding of the characteristics of patients likely to suffer such ADRs may help in reducing their occurrence. The ultimate safety decisions on medicines may need considerations of comparative benefit/risk evaluations between products for similar indications, so the complexity is great
Further information is available in the WHO (2002) publication
Several methods can be used to collect safety information. Spontaneous reporting forms the bedrock of all national pharmacovigilance systems. It is relatively inexpensive and provides a life-time monitoring of all medicines in all patients in any healthcare system. There are other systems including active patient follow-up e.g. Cohort Event Monitoring (CEM) that maybe useful when addressing specific research or pharmacovigilance queries.
Brief highlights of the various pharmacovigilance methods are given below (adapted from the ICH E2E Guidelines):
Passive surveillance
Spontaneous Reporting
Case series
Active Surveillance
Sentinel sites
Drug Event Monitoring
Registries
Stimulated Reporting
Comparative Observational Studies
The Non-experimental traditional epidemiologic methods are a key component in the evaluation of adverse events. A number of observational study designs are useful in validating signals from spontaneous reports or case series. Major types of these designs are:
Cross sectional study
Case control study
Cohort study (both retrospective and prospective)
Others
Targeted Clinical Investigation and Descriptive studies
The full guideline document can be downloaded from the
Any event that comes to public notice and threatens the health or safety of individuals or groups, or the reputation or stability of an organization. Crises usually erupt suddenly and dramatically; they require rapid and effective response and communications.
Management of a crisis requires not only resolution of the crisis event, but also very skilled management of the often intense emotions and outrage that the public may feel.
Unexpected or not?
Crises are generally regarded as sudden and unexpected, but many arise from conditions where there has been a history of neglect, carelessness or poor safety management; where warning signs and vulnerabilities have been ignored. Many crises were long in the making and were waiting to happen; many of these could have been prevented or the damage they caused reduced through early awareness, planning and action.
Identification of Signals >
What is a signal
What is a signal
In 1991, the WHO defined a signal as “Reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously”. Other definitions have since emerged from other scholars and publications. The Council for International Organizations of Medical Sciences (2010) defines a signal as “Information that arises from one or multiple sources (including observations or experiments), which suggests a new, potentially causal association, or a new aspect of a known association between an intervention [e.g., administration of a medicine] and an event or set of related events, either adverse or beneficial, that is judged to be of sufficient likelihood to justify verificatory action” Ultimately, a signal is a hypothesis.
Steps in Signal Detection
Setup >
Reporting of Adverse Drug Reactions (ADRs)
Reporting of Adverse Drug Reactions (ADRs)
Spontaneous reporting is currently the most common method of reporting ADRs. A case report in pharmacovigilance can be defined as: A notification relating to a patient with an adverse medical event (or laboratory test abnormality) suspected to be induced by a medicine.
A case report should (as a minimum) contain information on:
1
The patient: age, sex and brief medical history (when relevant). In some countries ethnic origin may need to be specified.
2
Adverse event: description (nature, localization, severity, characteristics), results of investigations and tests, start date, course and outcome.
3
Suspected drug(s): name (brand or ingredient name + manufacturer), dose, route, start/stop dates, indication for use (with particular drugs, e.g. vaccines, a batch number is important).
4
All other drugs used (including self-medication): names, doses, routes, start/stop dates.
5
Risk factors (e.g. impaired renal function, previous exposure to suspected drug, previous allergies, and social drug use).
6
Name and address of reporter (to be considered confidential and to be used only for data verification, completion and case follow-up).
Special free-post or business reply reporting forms, containing questions 1-6 mentioned above, can be distributed to healthcare professionals at regular intervals (for example, four times a year). Reply-paid reporting forms may be included in the national formulary, drug bulletin or professional journals. Also telephone, fax and electronic mail or internet may be easy means of reporting where reliable technology is available
Sample spontaneous reporting form
Different countries have different ways of collecting spontaneous reporting forms; ultimately it depends on the available resources. Some of these methods include;
Online reporting into a national database
Smartphone apps
Visiting regulatory centres to file reports
Telephone calls
Scanning/faxing of ADRs
Setup >
Financial Issues in Pharmacovigilance
Financial Issues in Pharmacovigilance
The importance of sustained financial resources for undertaking pharmacovigilance activities in each country cannot be overstated. This may be part of the overall budget of the Ministry of Health or the National Drug Regulatory Authority. It may be possible for national centres to obtain funding for targeted research especially in the area of the safety monitoring of medicines and vaccines of public health importance in the country or region. The following budgetary issues highlight budget lines that should be considered and these are intended mainly as a guide to assist countries. It should be modified and used appropriately.
Budget for setting up a standard spontaneous reporting system
Contact relevant authorities to ensure approval for the centre by outlining the importance of the centre and its purpose.
2
Design an ADR reporting form and start collecting data by distributing it to hospital departments, family practitioners, etc.
3
Produce printed material to inform health professionals about definitions, aims and methods of the pharmacovigilance system.
4
Create the centre: staff, accommodation, phone, word processor, database management capability, bibliography etc.
5
Educate pharmacovigilance staff on:
data collection and verification
interpreting and coding of adverse reaction descriptions
coding of drugs
case causality assessment
signal detection
risk management.
6
Establish a database for the storage and retrieval of ADR data.
7
Organize routine meetings in hospitals, academia and professional associations, explaining the principles of pharmacovigilance and the importance of reporting.
8
Promote the importance of reporting adverse drug reactions through medical journals, other professional publications, and communications activities.
common activities to be carried out in a pharmacovigilance centre
Crisis management >
The purposes of crisis management
The purposes of crisis management
1
To prevent crises happening
2
To manage crises that happen rapidly and effectively, minimizing damage to all parties, resolving problems and recovering stability and credibility.
Prevention
Every system and organization has actual or potential weaknesses and vulnerabilities arising from internal and external sources. Every aspect of management and safety systems, communications, data collection; staff motivation, knowledge and commitment; quality control, supplier management, and so on, needs to be examined for any potential failures, weaknesses or problems: what could possibly go wrong and how can it be anticipated and prevented?
The second aspect of prevention is being in a high state of alert for early, maybe weak signals of problems: a handful of ADR reports; a newspaper report of patient injury; new safety concerns emerging in another country; unexplained failure of treatment; anything that could escalate over time into a major crisis. Bureaucracies tend to stifle dissent and minor signs of possible trouble, sometimes leading to explosive problems later on: when, as so often, there were early signs of problems, how can an organization hold up its head and convincingly explain its neglect of them?
The third element of crisis prevention is reputation. An organization that has open communications with its audiences, conscientiously explains what it is doing at all times, is known and trusted, will suffer far less in crisis than one that is regarded as remote and secretive. A regulator that has thoroughly and openly communicated about the risks of medicines and its activities will be subject to much less criticism than one that has been defensive and distant; indeed some crises arise simply because patients, or the media, or healthcare professionals have been kept in the dark about what is going on and are angry and hostile when the facts eventually emerge. All organizations need to be actively communicating with their audiences at all times; when crises emerge, a familiar voice is more likely to be trusted, even forgiven.
A sudden batch of unexpected and serious ADRs
This is one of the commonest causes of crisis in pharmacovigilance for which every PV centre should plan. The issues and relationships and communications are more complex than in the case of fires, but the basic crisis management process is exactly the same:
Identify the risk: unexpected injury to patients and public outrage
Assess the risk: probable and serious
Initiate preventive measures: a constant state of high alert and attention for any evidence or allegation, however seemingly weak, from any source, of unexpected injury or death or other problems
Establish procedures for rapid investigation, review, analysis and decision-making about problems, and for communication with all stakeholders (this may require, for example, immediate access to pre-designated technical experts to be sent out into the field)
Review and rehearse procedures prior to crisis erupting.
Setup >
Logistics involved in the organization of the PV Centre
Logistics involved in the organization of the PV Centre
Staff
The expertise desirable in the routines of a pharmacovigilance centre includes:
Clinical medicine
Pharmacology
Toxicology
Epidemiology
However, a new pharmacovigilance centre often starts with only a part-time expert
usually a physician or a pharmacist
and some secretarial support.
It may soon become necessary to have one expert who is responsible for pharmacovigilance for most of his/her time and for secretarial assistance to be expanded. When the reporting of adverse reactions increases, staff resource requirements may be calculated by assuming that the average assessment time per case report is about one hour.
Human resources needed to start a Pharmacovigilance Centre
basic equipment needed for a pharmacovigilance centre
Continuity
Continuity in accessibility and service is a basic feature of a successful pharmacovigilance centre. The centre therefore needs a permanent secretariat, for phone calls, mail, maintenance of the database, literature documentation, coordination of activities, etc. Secretarial continuity may be achieved through collaboration with related departments.
Advisory Committees
A multi-disciplinary advisory committee is desirable, to support the pharmacovigilance centre with regard to the quality of the procedures in:
Data collection and assessment
Data Interpretation
Information publication
A network of experienced advisors in various specializations is helpful
Information service
The provision of a high quality information service to healthcare professionals is a basic task of a pharmacovigilance centre and a major instrument in the stimulation of reporting. For this purpose and for the assessment of case reports the centre should have access to a comprehensive and up-to-date literature source and information database.
Location of the centre in a large hospital usually has the advantage of a library within reach. National pharmacovigilance centres can have online access to the database of the UMC and be on the mailing lists of adverse drug reaction and drug bulletins produced by the World Health Organization and many national or regional centres throughout the.
Communications
A bulletin or newsletter distributed to all healthcare professionals or a regular column in reputed (medical and pharmaceutical) journals are good means for the dissemination of information. Prompt data-sheet amendments are important, but data-sheets may be printed infrequently and their educational impact may not be large. In urgent cases of sufficient importance ‘Dear Doctor’ letters may alert the profession.
Other Useful collaborations
It is always ideal to look out for other organizations that may be able to collaborate with your PV Centre to reduce the financial and logistic burden. For example, poison control and drug information centres share similar PV interests. It may be useful to develop a PV system in conjunction with these centres.
The WHO Programme for International Drug Monitoring (PIDM) and how to join >
The history of the WHO PIDM
The history of the WHO PIDM
The first practical international co-operation in drug monitoring started in 1968. The idea came up as a consequence of the thalidomide tragedy. In the 1960s it was discovered that, thalidomide could cause limb deformities in babies if ingested by mothers during pregnancy. This incident became the modern starting point of a science focusing on patient problems caused by the use of medicines. This science, and activities associated with it, is now most commonly called pharmacovigilance. The Sixteenth World Health Assembly (1963) adopted a resolution (WHA 16.36) that reaffirmed the need for early action in regard to the rapid dissemination of information on adverse drug reactions and led, later to the creation of the WHO Pilot Research Project with 10 countries, to develop a system, applicable internationally, for detecting previously unknown or poorly understood adverse effects of medicines.
The initial activities of the pilot project culminated in the current WHO Programme for International Drug Monitoring (PIDM) and has grown to become a global network of national pharmacovigilance centres around the world. Here is a global map of the current WHO PIDM Members.
The intention of the WHO PIDM is to ensure that early signs of previously unknown medicine-related safety problems are identified and information about them shared and acted upon throughout the world.
The WHO Programme for International Drug Monitoring (PIDM) and how to join >
How to join the WHO PIDM
How to join the WHO PIDM
A formal application to be admitted as a member of the WHO Drug Monitoring Programme should be sent to WHO Headquarters, Geneva, by the competent health authority of the country. The application should identify the institution and responsible person representing the country as a National Centre in the WHO Programme. You’ll find a sample application letter here
The steps involved in joining the WHO Programme are outlined in the flowchart below
The basic requirements to join are:
1. General acquaintance with the methodology of spontaneous reporting
A country joining the WHO Programme must have a programme for collection of individual case safety reports (ICSRs) in place, including reasonable funding for operations, appropriate staffing and technical facilities.
2. A national centre for pharmacovigilance
Only WHO member states can join the WHO Programme for International Drug Monitoring. Each state is represented by a National Centre authorized by the competent national health authority. In most cases the National Centre is part of the national drug regulatory authority but it may also be affiliated to a university institution, a hospital department or be integrated with a drug information or poison information service. A central technical advisory committee with expertise to evaluate reports and advise on suitable action is desirable.
3. Technical competence to fulfil reporting requirements to WHO
The main asset of the WHO Programme for International Drug Monitoring (PIDM) is its database (Vigibase) of adverse reaction case reports submitted by the participating countries. Case reports collected in the national drug monitoring programme must be submitted to the WHO Programme in a defined format. Before being admitted to the international scheme the National Centre has to demonstrate that it is capable of submitting data in the required format, as defined in the guidelines issued by UMC.
A new country is accepted in the WHO PIDM provided that individual case safety reports submitted to VigiBase from that country may be freely available for analysis by any investigator, according to policy determined by the WHO. (Patient and reporter identity is not recorded in the WHO database).
Identification of Signals >
Methods of Signal Identification
Methods of Signal Identification
There are essentially 2 methods by which signals can detected;
Case by case (qualitative signal detection) for individual reports
Statistical methods (Quantitative) for large databases
Clinical assessment of individual events
Careful, routine, standardized clinical assessment of individual reports with alertness to the possibility of a signal, offers the quickest method of identifying signals. This approach should be taken during routine review of incoming reports. During routine assessment of reports, if an assessor identifies an event and thinks that it could be a new type of adverse reaction, a search should be undertaken for records of other similar events to confirm the opinion. First, the national or WHO global database for Individual Case Safety Report (ICSR) should be checked for other similar reports or clinically related terms. Then the adverse reaction should be checked in appropriate reference sources. If there is no reference to the occurrence of the event as an adverse reaction, then the PV Centre should proceed with its investigation.
Clinical review of collated events
01. Regular review
All the events in the database for the drug(s) of interest (or class of drugs) should be reviewed at regular intervals e.g. each month.
02. Clinical presentation
This is facilitated by collating (sorting) the events by means of a computer programme into a clinically orientated structure so that the overall clinical picture of events occurring with the drug or regimen can be viewed. This is accomplished by sorting the event terms by the events dictionary codes.
03. Collating the events
After assessment, individual events should each have a term applied to it that is selected from the events dictionary. Most dictionary terms e.g. MedDRA, are coded in such a way that clinically related events can be sorted to appear together. The events can then be printed out or seen on the computer monitor in a systematic clinical structure.
Groups of related events are then seen clearly. For instance, for the investigation of cardiac failure as a possible signal, all possibly related events and conditions that might be associated with heart failure should be considered together. These would include cardiac failure aggravated, cardiac failure right, congestive heart failure, cardiac failure left, dyspnoea (assessed as of cardiac origin), peripheral oedema, jugular venous pressure increased, cardiomegaly, cardiomyopathy and heart valve disorders. The whole group of events should then be taken into consideration.
Identification of Signals >
Data Mining of Large Databases
Data Mining of Large Databases
Data Mining has been described as “any computational method used to automatically and continuously extract useful information from large amounts of data”. It is an important aspect of the knowledge discovery from data (KDD) process. Many use the expression “finding a needle in a haystack” to describe this activity. In pharmacovigilance, data mining is very significant in detecting Adverse Drug Events. Many established drug regulatory agencies use data mining techniques to detect ADEs. Case by case becomes difficult when you have large data, as you cannot assess thousands of cases every day; hence statistical methods have been developed to identify ADR-drug pairs that occur more frequently that you would expect Examples of include:
Association of pericarditis with practolol and not other β-blockers
Association of captopril and other angiotensin converting enzymes with cough
Association of terfenadine with heart rate and rhythm disorders.
01. Useful Databases for Data Mining
It is important to note that choosing a database is highly dependent on the PV centre and its specific resources. New PV centres may not necessarily have a large repository of data to choose from, but ideally, a dataset size is dependent on the data quality, the background frequency of the event and the strength of the association of the event with the drug. Some useful databases include:
02. Spontaneous reporting databases:
WHO global database for ICSRs ,Vigibase is the largest database of its kind in the world, and to date (October 2018), it holds over 18 million reports of suspected adverse effects of medicines, submitted, since 1968, by the over 150 member countries of the WHO Programme for International Drug Monitoring.
03. Other sources of data:
Electronic medical records
Prescription event monitoring and Claim database
Data-mining techniques
Some examples of data mining techniques include Clustering or database segmentation, predictive modelling, deviation detection etc. Currently in pharmacovigilance, “disproportionality analysis” is the common technique used by most centres with large databases of at least 100,000 reports.
Disproportionality uses all reports in the database as a background to predict how frequently you would expect an ADR-Drug combination. The disproportionality measure expresses the extent to which the reported ADR is associated with the suspected drug compared with all other drugs (or a subgroup of drugs) in the database. Under measures of disproportionality, two methods are used; these include the common Frequentist/classical measures and the more complex Bayesian statistics.
The Frequentist approach involve the calculation of relative reporting ratio (RRR), proportional reporting ratio (PRR) and reporting odds ratio (ROR) together with certain hypothesis tests of independence to determine association.
The Bayesian approach uses more complex algorithms such as the Bayesian Confidence Propagation Neural Network (BCPNN), Gamma-Poisson shrinker (GPS), Multi-item gamma-Poisson shrinker (MGPS) and Empirical Bayesian geometric means (EBGMs).
BCPNN
The WHO Collaborating Centre for International Drug Monitoring regularly scans the WHO global database for potential signals using its automated data mining program, the Bayesian Confidence Propagation Neural Network (BCPNN). It uses neural network architecture to scan incoming reports and identify unexpectedly strong dependencies between drugs and adverse reactions. This produces the disproportionality measure known as the Information Component (IC) value for drug–event combinations. A positive signal will have IC values that become more significant over time as more cases are included. If the IC value is positive IC>0 for a Drug-ADR combination, the combination is reported more frequently than expected IC values for drug-ADR combinations using data from the WHO global database of ICSRs is available for WHO PIDM members via the Vigilyze tool.
Proportional reporting ratios (PRR)
This is a method that uses software to measure the proportion of reports in the database with a particular drug–event combination and compares this proportion with that for the same event in the reports for all other drugs combined. If the PRR for a particular drug–event combination is significantly high, and it is not a recognized reaction, it may represent a signal.
These automated methods can strengthen a signal identified by clinical evaluation. They may identify signals that were missed during assessment of the reports and later review.
Data Mining can be a complicated process that requires a high level of expertise and huge amount of data, but it is a scientifically proven tool to detect signals at a faster and more accurate pace than others.
If you are interested in reading more about data mining, please look at the reference list for more details
References
Edwards, R., Lindquist, M., Bate, A. and Noren, N. (2006). Data Mining in Pharmacovigilance: A View from the Uppsala Monitoring Centre. p.Chapter 21.
Han, J., Kamber, M. and Pei, J. (2012). Data mining. Amsterdam: Morgan Kaufmann.
Liu, M., Matheny, M., Hu, Y. and Xu, H. (2012). Data mining methodologies for pharmacovigilance. ACM SIGKDD Explorations Newsletter, 14(1), p.35.
Poluzzi, E., Raschi, E., Piccinni, C. and De Ponti, F. (2012). Data Mining Techniques in Pharmacovigilance: Analysis of the Publicly Accessible FDA Adverse Event Reporting System (AERS). [online] Intech OpenScience. Available at: https://www.intechopen.com/books/data-mining-applications-in-engineering-and-medicine/data-mining-techniques-in-pharmacovigilance-analysis-of-the-publicly-accessible-fda-adverse-event-re [Accessed 8 Oct. 2018].
Wilson, A., Thabane, L. and Holbrook, A. (2003). Application of data mining techniques in pharmacovigilance. British Journal of Clinical Pharmacology, [online] 57(2), pp.127-134. Available at: https://www.ncbi.nlm.nih.gov/pubmed/14748811 [Accessed 26 Sep. 2018].
Witten, I. and Frank, E. (n.d.). Data mining. San Francisco, Calif.: Morgan Kaufmann.
Communication in PV >
Why is communication important
Why is communication important
Effective, skilled communication is vital in every aspect of pharmacovigilance. Without communication:
1
We cannot motivate health professionals to report suspected adverse reactions
2
We cannot collect the range and quality of information we need to protect patients and save lives
3
We cannot influence health professionals and help them achieve safer therapy.
Pharmacovigilance risks becoming a sterile, bureaucratic system when the vision of patient safety is buried in clerical routine, paper shuffling and administrative preoccupation. PV should be a lively, dynamic, ambitious enterprise, with creative communication at its heart, and a determination to make a real difference to the health and welfare of the world.
Communication in PV >
Communication flowchart
Communication flowchart
Communication in PV >
Methods
Methods
The means of communication we use should correspond to our specific countries and their preferred mediums of communication; these platforms should be widely accessible and attractive. They can include:
TV & Radio
Social media (Twitter, Facebook, etc.)
Internet, emails, RSS feeds
Journals and other publications
Printed leaflets, posters
Mobile phone applications
Peer-to-peer activities (e.g. workshops, disease-specific organizations, village meetings)
Colloquia or training programmes
One-to-one detailing or consultation
Using the appropriate means of communication can maximize the efficiency of your work and increase influence of your message on your target groups.
Repetition and variety
In this world of information overload, the best way to increase your influence and effectiveness when conveying important information is through repetition via different channels of media, using various methods. Examples of ineffective conveying of information where the message fades away is e.g. in public health campaigns. (Safe Sex: while a campaign is active, behavior changes and sexually-transmitted infections decrease; once it stops, behavior reverts, and infections rise again). We should ensure the message is continuously and effectively reaching the people and their awareness is constantly high. “Repetition is the mother of learning”
(nowhere is this more significant than in stimulating ADR reporting, see below).
Presentation and design
The design and presentations of our PV material is of fundamental importance. By investing in credible and visible messages that particularly capture people’s attention, we increase the likelihood of a person reporting an adverse event. The messages should be clear and simple in order to be memorable and effective. This can be achieved with little or no extra resources e.g. by assigning the project to an existing but creative employee, but is crucially important in building the future of pharmacovigilance. The addition of pictures and graphics can further capture the person’s attention.
There are some simple principles for making text look pleasant and readable on a page:
Leave wide margins and plenty of white (empty) space; don’t cram everything together
Use an attractive and appropriate typeface (font)
Use a font size which is easy to read and does not require perfect vision or a magnifying glass (nothing less than about 12 point is really attractive or easy to read for people with normal vision)
Use a larger font size for the priority aspects of the message (see next section) and, overall, for elderly or visually handicapped people
Give the page structure with bold headings and subheadings
Use graphics, charts, illustrations or photographs where possible and appropriate
Test your ideas and materials with your specific audiences
Structure, content and language
Official communication language, no less in PV than in other areas, usually is too formal, dense, long and complicated. The main substance is often buried in the midst of a welter of detail, much of which may be irrelevant to most of the audience.
Here there are some simple rules for making text as effective as possible:
State the main purpose of the document in the title and first paragraph
If you want recipients to do something (change their prescribing habits, for example) say so at the beginning
If there are several messages (e.g. in a patient information leaflet), summarize the most important minimum briefly and clearly
Provide supporting or explanatory detail only If absolutely essential
Demote non-essential evidence or detail or further information to the end of the document
Your recipients commit a significant part of their personal time to follow and understand your message. For this reason, it is of utmost importance that you convey the message quick and effectively, to capture their interest. In this way, they get an essence of what you have to say and even the most skeptical audience will commit more time to you. The first impression matters! Avoid delivering unnecessary information and always design your message according to your target group.
These principles apply to almost every kind of communication: letters, reports, warnings and advisories, emails, patient information or package inserts. Put the essential information in the beginning of the document (or web page) clearly, boldly and elegantly, and keep quite separate all the secondary, information and details.
Language and content
Generally speaking, following these principles will result in good writing:
Always prefer simple over complex language
Avoid formality of style; write simple and informal
Avoid jargon, acronyms, abbreviations wherever possible; always explain them if you include them
Keep sentences short (12-15 words where possible)
Keep paragraphs short (6 to 10 sentences, or less, where possible)
Use bullet points for all kinds of lists
Use bold headings and sub-headings which provide clear signposting for the content
Reading your material aloud (or having someone else read it to you) is the best and most reliable test of its quality
Key points:
Develop empathy for your audiences; understand their priorities and needs, their taste and their preferences through research and interaction
Shape and tailor your communication
Practice, retest your plans and materials
Choose a variety of methods
Repeat your message
Be creative and original in your design and presentation
A crisis is likely to be a very public event, with journalists, maybe politicians, and certainly the general public paying intense attention to it. There must be an effective communications plan in place:
Designated spokesperson and deputy, available at all hours during a crisis
Established contacts and channels of communication for major audiences
Facilities for rapid electronic, telephone or personal communication with critical audiences
Effective means of keeping staff and key affiliates updated
An organization must have a policy on crisis communications, ideally including a commitment to rapid and open information about what is happening and what is being done to manage the crisis. Organizations should pay attention to the suffering, anxiety or outrage of the public, and respond with credible, empathetic and effective messages. Distance, coolness, secrecy are disastrous tactics in almost all crisis situations. The priority is for frequent communication, even if it is only to describe what is being done to resolve the crisis. Never, ever say, ‘No comment,’ to enquiries; it will just make everyone think you have some dark secret to hide.
Many organizations (like PV centres) are “invisible” to the public; it is only at a time of crisis that they are thrust onto the public stage. Great public relations benefits at all times, but especially during crises and emergencies, accrue to organizations that have an established level of public profile and credibility throughout the course of their normal business. An organization that is known and trusted is likely to suffer much less damage at a time of crisis than one that is unfamiliar and not trusted. An active media relations programme will benefit most organizations all the time, and especially during crises.
About PV Resources
These Pharmacovigilance (PV) Resources are a collection of resources and information needed for the practice of pharmacovigilance. The main aim of its development is to ensure that PV practitioners in low- and middle-income countries get access to information on the processes and activities involved in PV from a trusted source.
Who can use these Resources?
PV practitioners
Students and Academics
Other stakeholders in PV
How to use these Resources
Take advantage of the resources in these Resources to start your own PV Centre, learn about various concepts in PV through our interactive system and take the quizzes to test your knowledge on them. You can also contact our PV experts for more information on specific topics!
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.
These Pharmacovigilance (PV) Resources are a collection of resources and information needed for the practice of pharmacovigilance. The main aim of its development is to ensure that PV practitioners in low- and middle-income countries get access to information on the processes and activities involved in PV from a trusted source.
What do I need to do if I want to set up a Pharmacovigilance Centre in my country?
Please refer to our page on setting up a PV Centre
What is the work of the WHO Programme for International Drug Monitoring (PIDM)?
The intention of the WHO PIDM is to ensure that early signs of previously unknown medicine-related safety problems are identified and information about them shared and acted upon throughout the world. More information on the programme is available on the “WHO PIDM” page
Where can I find information on various topics in Pharmacovigilance?
You can find useful resources on Signal Detection, Benefit Harm Assessment, and other related issues in PV on this site. We also provide you with several other educational material, publications and journals which may be of interest to you.
What are the common terms used in the area of Pharmacovigilance?
On this site you’ll find some common definitions used by PV workers worldwide. Most of these definitions have been incorporated into guidelines issued by the ICH, EMEA and other competent national authorities.
EMP/QSM (the Pharmacovigilance “department” of WHO)
The WHO Essential Medicines and Health Products (EMP) Department works with countries to promote affordable access to quality, safe and effective medicines, vaccines, diagnostics and other medical devices. Built on three main pillars – access, innovation and regulation – EMP promotes policies and technical capacities in low-resourced health systems, develops international standards for the manufacturing and regulation of health products and provides guidance for health systems everywhere to deliver them safely and cost-effectively.
WHO Collaborating Centre for Drug Statistics and Methodology
This Centre forms part of the pharmacoepidemiology department at the Norwegian Institute of Public Health in Oslo. The Centre was established in 1982, and is funded by the Norwegian government. It is responsible for developing, updating and maintaining the ATC/DDD classification system for medicines.
WHO Collaborating Centre for Pharmacovigilance, Morocco
The National Centre in Rabat, Morocco was appointed as a WHO Collaborating Centre for Pharmacovigilance in 2011. The Centre will conduct and facilitate regional and national pharmacovigilance training courses for Francophone, Eastern Mediterranean and Arabic countries, support the WHO normative functions related to pharmacovigilance and promote patient safety and assist WHO in the PV assessments and in the provision of technical support to Member States in pharmacovigilance and patient safety.
WHO Collaborating Centre for Pharmacovigilance in Public Health Programmes and Regulatory Services
In 2017, the Pharmacovigilance Programme of India (PvPI)- Indian Pharmacopoeia Commission (IPC), in Ghaziabad, India, became a WHO Collaborating Centre. The PvPI centre assists WHO by:
Support WHO to develop relevant tools and guidelines for enhancing pharmacovigilance practice in Low and Middle-Income Countries (LMIC) in Asia and beyond.
Contribute to capacity building of WHO member states to establish high-quality pharmacovigilance systems for medical products.
Scientific support to countries for pharmacovigilance in public health programmes (e.g. Tuberculosis, Neglected Tropical Diseases, Vector Borne Diseases, HIV-AIDS; Immunization Programme) and regulatory issues.
The Global Fund Against AIDS, Tuberculosis and Malaria (The Global Fund)
Financing mechanism for the three killer diseases. The Global Fund works in a transparent way which involves all stakeholders. It is run by an international multi-stakeholder governing board.
The Bill & Melinda Gates Foundation (Gates Foundation)
Works to help all people lead healthy, productive lives. In developing countries, it focuses on improving people’s health and giving them the chance to lift themselves out of hunger and extreme poverty.
The RBM Partnership is the global framework to implement coordinated action against malaria. The website is an excellent resource for all things malaria.
Founded in 1912, the International Pharmaceutical Federation (FIP) is the global federation of national associations of pharmacists and pharmaceutical scientists and is in official relations with the World Health Organization (WHO).
DIA is a neutral, non-profit, global, professional association of nearly 18,000 members who work in every facet of the discovery, development, and life cycle management of pharmaceuticals, medical devices, and related products.
The Drug Safety Research Unit (DSRU) is a leading independent academic research organisation internationally renowned for its work in Prescription Event Monitoring (PEM), Drug Safety and Educational Activities for more than two decades.
Management Sciences for Health, Inc. (MSH) is a private, non-profit educational and scientific organization working to close the gap between knowledge and action in public health.
European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP)
The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP)is a project led by the European Medicines Agency and developed in collaboration with European experts in the fields of pharmacoepidemiology and pharmacovigilance. Its goal is to further strengthen the post-authorisation monitoring of medicinal products in Europe.
The Brighton Collaboration website provides information on vaccine safety and is the leading source for standardized case definitions of adverse events following immunization.
The Institute for Safe Medication Practices (ISMP) is a non-profit organization devoted entirely to medication error prevention and safe medication use. The organization is known and respected worldwide as the premier resource for impartial, timely, and accurate medication safety information.
Medicines and Healthcare Products Regulatory Agency (MHRA), UK
This is a useful resource containing information and several documents targeted mainly at UK practitioners but nonetheless very useful for other countries.
New Zealand Medicines and Medical Devices Safety Authority (Medsafe)
This is a good resource for datasheets for medicines and patient leaflets. It also has articles in Prescriber update, many of which come from the National Pharmacovigilance Centre.
Council for International Organizations of Medical Sciences (CIOMS)
CIOMS is an international, non-governmental, non-profit organization established jointly by WHO and UNESCO It publishes several standardized materials on pharmacovigilance. The CIOMS website also the standard “CIOMS ADR Reporting Form” that several pharmacovigilance have utilized to provide the content for designing their own ADR reporting forms.
International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
ICH is a project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of pharmaceutical product registration. Detailed information on ICH guidelines and requirements are available here.
The information obtained during clinical trials of new drugs is by design insufficient to provide a comprehensive overview of its safety and effectiveness in routine clinical practice (limitations of pre-licensure clinical studies include short duration, small numbers of patients, exclusion of patients with other diseases, exclusion of pregnant women, infants and the elderly).The long-term safety of a medicine is thus only known when the drug is being used widely in a population and its safety is being monitoring by organized local, national and international efforts.
Many adverse drug reactions (ADRs) are preventable and a good knowledge of pharmacology, good prescribing practices and the provision of simple tools and facilities would reduce drug-related morbidity and mortality in humans. However, there are some ADRs which are unknown, unpredictable and not preventable though an understanding of the characteristics of patients likely to suffer such ADRs may help in reducing their occurrence. The ultimate safety decisions on medicines may need considerations of comparative benefit/risk evaluations between products for similar indications, so the complexity is great
Further information is available in the WHO (2002) publication
Many adverse drug reactions (ADRs) are preventable and a good knowledge of pharmacology, good prescribing practices and the provision of simple tools and facilities would reduce drug-related morbidity and mortality in humans. However, there are some ADRs which are unknown, unpredictable and not preventable though an understanding of the characteristics of patients likely to suffer such ADRs may help in reducing their occurrence. The ultimate safety decisions on medicines may need considerations of comparative benefit/risk evaluations between products for similar indications, so the complexity is great 
