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13 Collaborative Approaches toEstablishing andImplementing Pharmacovigilance Systems
297
established medicines, or newly developed medicines. What society should be trying to achieve in
pharmacovigilance has recently and more eloquently been dened as follows:
‘pharmacovigilance monitors how different
humans are exposed to a myriad of medicines in
different ways, for different reasons, in differing
situations, using a variety of methods and doses.
The science is about detecting not just harm
caused by products and substances themselves
but also the effects of errors, irrational use, and
other almost limitless variables in how they are
consumed. Its mission is to constantly examine
and learn from this experience to nd out why
one outcome is better than another and how to
prevent or mitigate problems’ [1].
A fundamental requirement for effective pharmacovigilance is integration into the regulatory
system for medicines throughout their life cycle.
No medicine should be sold without some form
of prior licencing or registration by a government. However, the quality of regulatory practice
varies across the world and with different medicines. If product quality cannot be assured, no
amount of pharmacovigilance can compensate.
Product quality complaints may concern product
purity, stability (shelf-life), and potential for
transmission of infectious agents. Lack of therapeutic effect for the authorised indication may
also indicate quality problems [2]. The relationship between pharmacovigilance and product
quality is important and is best illustrated by
three examples (Fig. 13.1).
Ideally, for a new medicine, pharmacovigilance should start with the preclinical testing
phase through to the pivotal clinical trials
required to obtain a marketing authorisation.
Each phase of development does not have xed
start and end dates so that preclinical testing and
clinical pharmacology studies may be extended
into the post- marketing phase. A vital part of
pharmacovigilance is communicating information effectively to users and HCPs and taking
regulatory action when necessary to protect public health. This is referred to as the Summary of
Product Characteristics (in the UK or EU) or
Package Insert (in the US) and may be accompanied by a patient information leaet. This latter
requirement is not necessarily fullled in lowincome countries. Once authorised, a pharmaceutical company (within which will be the
marketing authorisation holder [MAH]) can
market the medicine, either directly or through
partners, and post-authorisation surveillance
begins [3].
3 A Brief History ofHow Our
Current Global
Pharmacovigilance System
Arose
Following the thalidomide crisis in the early
1960s, there was much regulatory activity about
how to monitor the safety of medicines with the
focus on spontaneous reports of suspected
adverse reactions for marketed medicines.
However, there was no coordination resulting in
different regulations, denitions, and reporting
forms with no attention to systems thinking or
design as that science was still in its infancy [4,
5]. One problem, among many other challenges,
for a country’s pharmacovigilance regulator, was
what to do with foreign cases and multiple positions were adopted nationally. As a result, during
the 1960s and 1970s, each country worked out
their own schemes for collecting and managing
spontaneous reports for marketed products [6,
7]. Such disjointed procedures consumed much
effort and time as legislation had to be drafted
for each country with some countries making
signicant organisational changes. In addition to
no harmonisation about what to collect and how
to manage data both for marketed and investigational products, there was no agreement about
how and when regulatory authorities should be
kept informed. That is why in the late 1980s,
regulators from the three main regions (US, EU,
and Japan) had joined with industry to form the
International Council (previously Conference)
for Harmonisation of Technical Requirements
for Pharmaceuticals for Human Use (ICH).
ICH's mission is to achieve greater harmonisation worldwide to ensure that safe, effective, and
high-quality medicines are developed and registered in the most resource-efcient manner.
298
cell
eting
B. Edwards and A. Caro-Rojas
QUALITY EXAMPLE 1: In 1979, a
urinary antiseptic called oxalinic
acid, was shown to cause rapid
resistance in previously sensitive
bacteria causing lack of effect. As
a result, the licence was suspended.
QUALITY EXAMPLE 3: Between 1998 and 2004, a change in manufacturing led to an increase in pure red
aplasia (PRCA) associated with erythropoietin alpha which has never been fully explained. The mark
authorisation holders were required to monitor cases classified as lack of effect carefully to capture all PRCA
cases in case this important adverse reaction has been missed.
Fig. 13.1 Examples illustrating relation between pharmacovigilance and product quality
Harmonisation is achieved through the development of ICH guidelines through a process of
scientic consensus with regulatory and industry
experts working side-by-side. Key to the success
of this process is the commitment of the ICH
regulators to implement the nal guidelines.
These ICH guidelines form the foundation for
international regulatory pharmacovigilance [8].
Based on the recommendations of the Council
for International Organizations of Medical
Sciences (CIOMS) and ICH, common denitions
and standards for reporting for individual cases
and aggregate datasets were developed that were
then implemented in the ICH regions. However,
variations in the detail remained between the
regions so that although the principles have been
harmonised through ICH, the regulatory details
about implementation can still vary, often for reasons which remain obscure.
An important step in harmonising EU-wide
QUALITY EXAMPLE 2: FDA pools data about product quality
obtained from GMP inspections, adverse events, and substandard
pharmaceutical bioequivalence issues. As a result, FDA withdrew
generic bupropion, and metoprolol in 2014 and methylphenidate in
2015 after reports of subtherapeutic outcomes which is when a
product does not perform as expected because of issues with the
active pharmaceutical ingredients or excepients or low-quality
manufacturing practices.
modules covering major pharmacovigilance processes with modules covering product- or
population- specic considerations such as vaccines and biologicals. There are special chapters
dedicated to pregnancy and breast feeding and the
geriatric population. As GVP applies to EU market
authorisation holders wherever they market their
medicines, this legislation has had global impact
either through the afliates of multinational companies or through the implementation of pharmacovigilance agreements with partners [10, 11].
It is important to remember that even now
there are still countries, such as those with a lowincome, whose pharmacovigilance systems are at
an early phase of development. There are also
some countries which have not started talking
about medicine safety. That means within the
International Society of Pharmacovigilance we
often nd a lack of understanding amongst HCPs
about pharmacovigilance.
multiple national systems was the creation of the
EU pharmacovigilance system starting on January
1, 1995, with the European Medicines Agency
(previously called EMEA, now EMA) and a central database, EudraVigilance which came later
4 The Move fromPassive
Surveillance toActive Risk
Management
[9]. A further major change in EU pharmacovigilance occurred with a new legislation in 2012
(Directive 2010/84/EU). This legislation established Good Pharmacovigilance Practices (GVP)
which are legally binding and are divided into
In the 1990s, there were several high-prole studies showing the extensive harm caused by all
forms of medical errors including harm from
medicines [12–14]. This led to a recognition that
13 Collaborative Approaches toEstablishing andImplementing Pharmacovigilance Systems
299
pharmacovigilance needed to be reformed by
starting the process earlier before a marketing
authorisation is granted, and that a change in philosophy was needed towards demonstrating
safety as opposed to looking for harm. This led to
the creation of ‘risk management’ strategies to be
applied to the development and marketing of
medicines throughout their life cycles. These risk
management strategies have common themes
including dialogue between stakeholders and the
creation and maintenance of risk management or
minimisation plans which can be implemented
once a marketing authorisation is granted. These
ideas were rst discussed in an important seminal
document produced by US FDA in 1999 entitled
‘Managing the Risks from Medical Product Use:
Creating a Risk Management Framework’.
Recommendations included heightened surveillance of products on the market, further epidemiological studies, and enhanced communication.
The report emphasised the need for greater systems integration because risk management is a
shared responsibility with industry, HCPs,
patients, other government departments, healthcare delivery system, and professional organisations. A safe product is one that has reasonable
risks, given the magnitude of the benet expected
and the alternatives available [15].
Throughout the decade from 2000, risk management developed into active planning and risk
minimisation and ICH then produced ICHE2E
guidelines which have been implemented in each
of the main ICH regions [16]. The US emphasised risk minimisation whereas the EU and
Japan developed the concept of full risk management. Despite these ICH guidelines and denitions, there is no internationally agreed denition
for integrating risk management for both pharmaceuticals and devices together so that separate
legislation for their regulatory systems remains.
Regionally and nationally, regulators have developed their own practical strategies for blending
the collection and analysis of safety information
for medicines and devices with measures to
reduce risks to patients in their jurisdiction [17].
The US FDA’s denition of risk management is
useful for all involved with medicines and devices
by describing the continuing process of minimising risk throughout the product’s life cycle to
optimise benet–harm balance [18]. First, benets and harms are evaluated, then risks minimised
through appropriate interventions, which are
evaluated and revised as information is gathered
about impact. A risk minimisation tool is a process, or a new system, intended to minimise
known risks. This may be enhancing the communication of further guidance about prescribing,
dispensing, and/or using product in most appropriate circumstances or patient populations. The
categories of tools which can be discussed
between stakeholders include:
1. Targeted education and outreach, specically,
to increase knowledge for key people or
groups is often used especially if it can be
linked to continuing medical education. For
the industry, these can be introduced in disease management or patient access
programmes.
2. Reminder systems in addition to targeted education that prompt, remind, double check, or
otherwise guide HCPs and/or patients in prescribing, dispensing, or receiving products in
ways that minimise risk.
3. Performance-linked access systems are those
which link access to product to laboratory
testing results or other documentation.
Points to consider when choosing a tool to
minimise risk require discussion and cooperation
between stakeholders to try and ensure that the
optimal tools are selected and implemented for
each healthcare system. These tools should maintain widest access to a medicine while creating
the least burden on both the healthcare system
and relationships between HCPs and patients.
This means that sponsors of such tools, which are
usually MAHs, should obtain input from key
groups about the feasibility of implementing and
accepting tools in usual healthcare practices, disease conditions, and lifestyles. This includes
compatibility of tools with current technology
and that they are applicable in both outpatient
and inpatient settings with accessibility to
300
B. Edwards and A. Caro-Rojas
patients in diverse localities, including nonurban. Tools should be consistent with existing
tools or programmes that have been shown to be
effective with similar products, indications, or
risks. The MAH for a medicine usually has a
responsibility to periodically evaluate the effectiveness of risk minimisation and report to the
supervising regulatory authority at agreed intervals [19, 20].
5 Impact ofSocial Media
andtheInternet
onPharmacovigilance
One evolving aspect of the global pharmacovigilance system which involves many of us has
been the impact of social media and the internet
because patients, carers, and their families can
generate information concerning safety and
effectiveness of medicines. However, such
social media data are unstructured and lack
quality standards. Key issues around patient
self- generated reports on social media are credibility and origin of reports with concerns about
inadequate and inconsistent data requiring additional follow-up which in turn is very difcult
[21, 22]. It is uncertain how best to integrate
social media ‘AE’ reports with those obtained
from more standard sources, especially to identify duplicates and map multi-lingual data which
may use colloquial and slang terminology.
Another concern is the potential bias due to the
reporter population [23]. Of the many social
media users, only a small percentage (1%) specically report adverse events, while most others occasionally contribute or observe. Many
elderly individuals, constituting a large demographic of prescription medication users, may
not use social media or use it in a different way,
creating a strong user bias for pharmacovigilance using social media.
From the published evidence, it appears that
many tweets and Facebook postings would have
to be examined to identify any important new
information relevant to benets and harms. When
social media has been examined and AEs identied, they are usually labelled and non-serious.
An occasional new ADR can be found. As
described in EU Good Pharmacovigilance
Practice module VI, there is EU regulatory consensus about MAH sponsored social media activities so that cases of suspected adverse reactions
from the internet or digital media should be handled as spontaneous reports. However, assessment of these cases reveals that it is difcult to
identify duplicates and validate individual case
components such as ‘reporter details’, severity,
and seriousness which have different meanings
with these postings and follow-up is in practice
very difcult. As a result, there remains regulatory uncertainty about how to handle information
from non-sponsored sources (e.g. social media
listening, noncompany website) if information
cannot be structured into an individual case
safety report or an identiable product complaint
[24].
6 The Importance ofQuality
Systems andHuman Factors
forPharmacovigilance
In pharmacovigilance, there is a need to pay
close attention to the design of appropriate
processes and quality of those actions required
for the collection, collation, and evaluation of
good quality information, which can be transformed into good-quality data. A common
medical terminology, The Medical Dictionary
for Drug Regulatory Affairs (MedDRA), is
used by regulatory agencies and the industry
for supporting transfer of information [25].
These data form the basis for how the pharmaceutical sector assesses the benets and harms
of a medicine. This up-to-date information
needs to be communicated to relevant HCPs
and patients in a way so that it can be interpreted unambiguously, which is a huge challenge with variable results across the world
[26, 27]. No single system of surveillance such
as spontaneous reporting will pick up every
13 Collaborative Approaches toEstablishing andImplementing Pharmacovigilance Systems
301
problem which is why we require additional
epidemiological data to help us, for example,
understand the prole of diseases in the
intended target population as well as the frequency of serious medical events and mortality
rates, which can confound causality assessment of suspected adverse reactions. This epidemiology is especially important for orphan
medicines for rare diseases where a low number of patients makes ADRs difcult to distinguish from background adverse events.
Every national pharmacovigilance system
will have its own needs based on some fundamental principles that form the basis of the current EU Good Pharmacovigilance Practices and
system that are in place today in Europe [28,
29]. However, as with many healthcare areas,
there is increasing pressure to do more with less.
Every country has limited resources with respect
to the size of the pharmacovigilance tasks that
face them. This means that we can never achieve
everything that we want in pharmacovigilance,
so that priorities must be set, and expectations
of stakeholders carefully managed. On top of
this, there have been numerous advances in
developing new medical technologies with a
proliferation of new and complex products. This
means the system struggles to keep up to date
and nd the necessary expertise to assess and
monitor evidence from new medicines derived
from innovative technologies. In addition, there
is worldwide shortage of professionals working
full time in pharmacovigilance and so available
expertise must be used prudently, especially in
low-income countries. This makes it imperative
for all of us in pharmacovigilance to adopt efciencies, leverage the work of others, and collaborate across regulatory authorities and
institutions to achieve better regulation and
oversight over national markets for medicines.
Thus, the less money available for a country, the
more important good-quality design is for a
country’spharmacovigilance system as such a
country can ill afford waste and duplication of
effort. These challenges led to the understand-
ing that pharmacovigilance should be implemented as a quality system which is exible,
adaptable, and t for purpose for each organisation and each country [30]. This in turn requires
cooperation and collaboration by all participants
in a system.
When discussing a system, it is important
to examine the relevance of human factors otherwise known as ergonomics. These are both
dened as the scientic discipline concerned
with the understanding of interactions among
humans and other elements of a system, and
the profession that applies theory, principles,
data, and methods to system design to optimise
human well-being and overall system performance [31]. In pharmacovigilance, we consider
patient safety includes safety of medicines,
which means focusing attention on the patient’s
quality of life and how it is affected by medicines in real life, beyond the pharmacology of
how medicines affect patients. Additionally, we
must include those who are managing medications such as HCPs and patients, by examining
their limitations, cognitive biases, and ignorance
about medication risk. In healthcare, some concepts such as human-centred care and humanism
are related and impact safe use of medicines.
Each pharmacovigilance system requires
strategies and plans to ensure continuity and
enable prompt recovery from any type of disruption such as pandemics, natural disasters, or
conict. Codes of ethics and conduct supported
by monitoring and enforcement, including sanctions for misconduct are also important in a
pharmacovigilance system. There should not be
inconsistencies between different policies
across the wider national and international systems as this can result in barriers to implementation and wasted effort. Unfortunately, lack of
harmonisation remains a signicant issue.
Therefore, goals of any pharmacovigilance system should be aligned with the health goals both
nationally and internationally which can be
summarised as six main components as
described in Table 13.1.
302
B. Edwards and A. Caro-Rojas
Table 13.1 Components of any pharmacovigilance system
I.
An adequate and appropriate pharmacovigilance policy with strategic aims to meet the public
health needs of a country. This may include the following:
Identification of the existence of current, future, and emerging hazards
Determination of which hazards pose the greatest risks to human health or the
environment
Development of effective strategies to manage risks including how to measure the benefits of
regulatory action and assess unintended consequences
Allocation of resources rationally and effectively
Stakeholders recognise how their role is involved in the system, what their responsibilities are
and act appropriately
II.
Pharmacovigilance processes need to be defined in sufficient detail to describe how the main
system outputs are created to a pre-defined quality to enable the following:
Effective information management systems that involve efficient case management and filing and
archiving of documentation and evidence with timely retrieval
Continuous and timely information on the clinical expression of ADRs
Adequate information on at-risk groups and underlying mechanisms and risk factors such as
pharmacogenomics
Analysis of causality based on algorithms, and approaches blending human factors and complex
system sciences
Rapid and precise detection of important signals
A sufficiently precise estimate of risk to allow valid benefit-risk evaluations and comparisons of risk
Ability to respond and communicate robustly to important safety concerns with a medicine within a
reasonable timeframe, including detailed risk communication and interaction with journalists and media
Actions to minimise the risk, such as educational campaigns and up-to-date information for HCPs and
patients or regulatory actions su
ch as a change in authorisation and labelling or access arrangements
III.
Definition of scope of product responsibility and areas to be covered including territorial
jurisdiction
A system flexible enough to adapt to all therapeutic areas including clinical trial safety, compassionate
use, and post-authorisation surveillance; consumer products including nutraceuticals, herbals, natural
products, and cosmetics; counterfeit strategy
Appropriate oversight of promotional and marketing activities of the pharmaceutical industry and
other sectors to ensure fair and balanced messaging about a medicine
13 Collaborative Approaches toEstablishing andImplementing Pharmacovigilance Systems
Table 13.1 (continued)
IV.
Sufficient staff who are trained and competent working in a motivational and learning
culture
Organograms and diagrams of organisational structure to demonstrate accountability and governance
relationships
Roles and responsibilities defined in job descriptions
Available expertise in workload, resource, and financial management
Continuous training considering best evidence in pharmacovigilance
V.
Ability to monitor and report on pharmacovigilance performance through system reviews,
audits, inspections, and investigations when normal processes fail
VI.
A fair and risk-proportionate system for regulating the pharmaceutical industry to ensure
marketing authorisations are kept up to date with variations and renewals, individual case
and periodic reports are assessed, and product risk is adequately managed through
communication and other risk minimisation measures
International experience suggests that pharma-
7 The Need forBetter Capacity
Building
inPharmacovigilance
covigilance is often only as strong as the available resources for activities such as training and
education the availability of which in turn inu-
ences implementing a quality system. Training
A large gap remains in pharmacovigilance
capacity and expertise from one country to
another emphasising the need for cooperation
and team working between all stakeholders
[32]. Experience from organisations such as
the World Health Organization (WHO) shows
that capacity develops in phases and over time.
Factors such as the level of development and
legal basis of the pharmaceutical sector, appropriate regulations, and the availability of trained
staff, infrastructure, and nancial resources
inuence the size and sophistication of the pharmacovigilance system and its ability to carry out
various pharmacovigilance functions [33, 34].
can be in the form of manuals, videos, work-
shops, courses, simulation learning, case-based
learning, or on-the-job learning. Such training in
pharmacovigilance should be incorporated in a
country’s medical curricula for training of HCPs
[35]. Human resource barriers to implementa-
tion of a pharmacovigilance system include
overburdened staff, a high staff turnover, the
mobility of staff between jobs, the mobility of
patients between different healthcare facilities,
and inadequate allocation of healthcare resource
within and between countries. Poorly developed
technological infrastructure such as a slow
internet can undermine the system.
303
304
B. Edwards and A. Caro-Rojas
8 Why Communication,
Collaboration,
andCooperation Are
Essential
forPharmacovigilance
As already explained above, those of us who
work in pharmacovigilance, as in many other
aspects of public health, are expected to do
more with less. This makes it imperative to
adopt efciencies, leverage the work of others,
and collaborate across regulatory authorities,
other government departments, healthcare systems and institutions to achieve better pharmacovigilance systems with adequate scientic
and regulatory oversight of national markets.
That is why the WHO has stressed that we all
have a responsibility to strengthen the system
by fostering interdependent engagement
among countries and national and exogenous
stakeholders. We need intelligence and information mechanisms to improve communication between national regulatory authorities,
state pharmacovigilance centres, patients,
HCPs, policymakers, and the public with
respect to supporting the safe use of medicines.
At an inter-governmental level, the pharmacovigilance system should interface with the
environmental agency pricing and reimbursement and enforcement services including the
police and customs. More broadly, pharmacovigilance centres need to interact with the
many different parts of the pharmaceutical
industry such as parallel importers, distributors, and wholesalers as well as professional
bodies for healthcare professionals. All these
groups should aim to provide safe and effective
medicines to patients and so should be looking
for synergies between their own policy or business objectives and be conscious of mixed or
conicting messages about the benets and
harms of medicines.
9 The Role
ofthePharmaceutical
Industry andRegulators
The pharmaceutical industry consists of more
than just the large multinational research and
development companies which provide the most
familiar image. The industry is a complex
arrangement involving distributors and wholesal-
ers, importers under special licence such as paral-
lel imports, as well as vendors such as contract
research organisations and consultants. There are
multiple industry bodies, and there is no one
body that speaks as the ‘voice of the industry’ or
who acts as a leader. Through pharmacovigilance
regulation and guidances, industry requires up-
to- date clarity from regulatory authorities about
their expectations concerning what submissions
should occur within what timeframes with timely
and constructive regulatory feedback. The phar-
macovigilance regulator must optimise the rela-
tionship with the industry through mutual respect
for their respective roles without the regulator
compromising their impartiality and indepen-
dence. Through constructive dialogue, between
all interested parties, practical risk minimisation
measures can be designed where they are
appropriate.
Clarication of regulatory expectations about
how industry should implement pharmacovigilance regulations can be achieved through issuing
guidances, newsletters, public presentations, and
setting up an information service for industry.
The sort of pharmacovigilance topics which can
cause uncertainty are expectations for a national
qualied person for pharmacovigilance, what
13 Collaborative Approaches toEstablishing andImplementing Pharmacovigilance Systems
305
reporting should occur between submission of a
marketing authorisation and its approval, arrangements for electronic reporting and periodicity of
periodic report submission. In addition, the pharmacovigilance regulator can help the industry set
its own pharmacovigilance priorities stressing
the importance of signal detection and the obligation to report all relevant safety information to a
regulator and what relevant means.
Regulatory safety actions may include, in
extreme cases, restricting indications, suspension,
withdrawal, or revocation of the marketing authorisation. More often these actions involve amendments to the package leaet, labelling, and
summary of product characteristics (SPC) (safety
variations) and education about proper use for the
HCP and patients [36]. There are multiple organisations in many national systems who inuence
the safe and effective use of medicines both preand post-authorisation. For example, in the United
Kingdom, as well as the MHRA, the National
Institute for Health and Clinical Excellence makes
safety recommendations as dothe various National
Health Services (NHS), professional bodies such
as the Royal Colleges, and professional regulators
such as the General Medical Council and General
Pharmaceutical Council. However, there is usually
just one regulatory authority who issues marketing
authorisations and directly regulates MAHs in one
market.
To help get the best out of industry, engagement requires having a high-level understanding
of how a company commercialises a product to
enable better integration of risk minimisation
solutions. Such commercial activities include
market research, patient support programmes,
and product promotion. There is an increasing
number of company initiatives concerning patient
and public engagement, which should be welcome although processes need to be transparent
about objectives, funding, and outcomes. HCPs
should better appreciate the heterogeneity and
complexity of the industry and their ethical obligations. This will help them understand about
who they are dealing with in a company and identify where they have common priorities without
compromising ethical behaviour and impartiality
in the choice of a medicine [37].
10 Interactions Between
theRegulators
andtheHealthcare System
Those within government with a responsibility
for pharmacovigilance regulation would be
expected to coordinate across different stakeholders to monitor, evaluate, and reach common
decisions about medicines [38, 39]. This includes
taking a lead in initiatives relating to electronic
information networks, data standards, and terminology to facilitate communication. There may
be legitimate differences to explain why the
licensing and pharmacovigilance systems do differ [36]. Information about the benets and harms
of a medicine obtained in a certain country (e.g.
the country of origin of the drug) may not be relevant to other parts of the world, where circumstances may be different [26]. Safety of a
medicine will be impacted by genetics, diet, and
traditions of the people. The end nished product
may arise from a country outside direct supervision of a regulator. Indeed, components of a
medicinal product (such as the carton and other
packaging) may come from different sources.
Domestic manufacturers may be operating to a
different pharmacopeia resulting in pharmaceutical quality and composition (excipients) of locally
produced pharmaceutical products. The package
insert for HCPs may differ regarding indications
and dose. The use of medicines which are not
regulated (e.g. herbal remedies) may create special toxicological problems, when used alone or
in combination with other medicines, posing challenges to harmonisation. Thus, socio-political
attitudes to how medicines are regulated and how
patients and families can access medicines inuence the conduct of pharmacovigilance. This
makes collaboration between all the stakeholders
even more essential for pharmacovigilance systems to function effectively. Additionally, the
restricted resources of regulatory agencies, manufacturers, and hospitals, particularly in lowincome countries, means it is difcult to enact
both vigilance and preventive actions.
Developing national pharmacovigilance systems requires close interaction between the regulatory and the healthcare systems to collect
306
B. Edwards and A. Caro-Rojas
continuous and timely information on the clinical
expression of ADRs [39, 40]. This may include
setting up centres for the collection and evaluation of suspected adverse reactions and reports of
misuse and abuse. Where they exist, toxicology
and poisoning centres play an important role as
well as being the experts in the management of
overdoses. The pharmacovigilance regulator may
want more information about underlying mechanisms and at-risk groups for suspected adverse
reactions which requires discussions about feasible modes of data collection and study. This may
involve collection of biological material such as
is required for pharmacogenomics. Agreement is
required about how best to record medication
errors and what should be public health priorities
which in turn will be translated into priorities for
the pharmacovigilance system. Should the pharmacovigilance regulator or pharmacovigilance
centre identify a safety concern with a medicine,
discussion with relevant healthcare stakeholders
is needed to identify and implement practical risk
minimisation measures. This may include a collaborative approach with HCPs and patients
about how best to communicate risk and newly
emerging safety issues.
11 The Role ofAcademia
andthePlace ofScientic
Societies andProfessional
Bodies ofHealthcare
Professionals
HCPs and academia provide an important source
of expert advice, analysis, and opinion within the
pharmacovigilance system especially as many
are involved in treating patients or undertaking
drug safety and pharmacovigilance research
activities. By directly or indirectly working
closely with those who use medicinal products,
they may be more in tune with real-life clinical
use of medicines and may propose original solutions to improve use. They may take a position on
safety issues themselves as well which may not
be aligned with the regulatory view [41, 42].
However, they have an ethical obligation to
ensure that messages for users are evidence-
based, coherent, and consistent. In undergraduate
healthcare professional training, it is still uncommon in many countries to have a specic module
for pharmacovigilance [43, 44]. Where it does
appear in training for healthcare professions then
it usually involves pharmacology or clinical risk
management of patients with inadequate emphasis about the sociotechnical system that supports
medication safety [45–47]. A collaborative
approach with patients and their families means
an active approach can be taken to minimise the
risk of adverse effects and if it is possible to prevent irreversible harm which should be the common aim for all.
As regards formal undergraduate and postgraduate training, this is more limited and is
usually conned to short courses. Apart from
the EU programme in Pharmacovigilance and
Pharmacoepidemiology, very few universities
offer a Masters or a PhD about pharmacovigilance topics. This means there are few options
to develop deeper research into pharmacovigilance to critically evaluate current scientic
approaches, and the quality of the system. Indeed,
there are only a few academic departments with
dedicated research groups who are critically evaluating pharmacovigilance regulations to assess
whether their implementation has achieved their
public health objectives or whether implementation could be improved.
Collaboration among stakeholders, who manage and use medicines regularly, should produce
better-dened information for decision-makers
and feed the system with a different and a more
elaborate worldview. Academic societies can help
with comparative benet–harm assessments and
develop treatment algorithms in a way regulators
cannot as they focus on individual MAHs. As
HCPs dispense, prescribe, and use medicines, it is
important for them to understand how intrinsic
human factors, such as cognitive bias, fatigue, and
stress, impact decision-making so individuals can
mitigate against any unwanted impact on prescribing or using a medicine safely [48, 49]. The
inclusion of teaching about human factors and
complex systems in academia could help us all to
better understand the risks from medicines, not
just as a product problem, but as a complex socio-
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