DECEMBER 2017 ISSUE 77

The quest
for evidence
Online PV courses • Social media campaign in
Kuwait • New VigiFlow • Pharmacogenomics
Illicit drug reactions • Duplicate detection
WEB-RADR reporting app

I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 1

 Director´s message Contents

A
CCORDING TO THE WORLD HAPPINESS REPORT,
published by the UN Sustainable Development
Solutions Network, the main factors found to support
happiness are: caring, freedom, generosity, honesty,
health, income and good governance. Sweden is currently
Is sustainability compatible with continued economic growth?
If economic growth continues to rely on depletion of non-
renewable resources, who are we kidding? I come to think of the
so-called pyramid schemes of the 1980s where a few people made
a fortune while a large number of people lost all their money. Too

16.
ranked the 9th happiest country in the world; and I am acutely often, society seems to operate like that. We need to start a major

aware of the privilege I enjoy, living in a country that is free
from war and famine, and where most of its citizens have
the prospect of a long, healthy and fulfilled life.
Does it mean that all Swedes are happy all the
time? No, it does not. But there is a link between
health and happiness; this is reflected in the
WHO definition of health as ‘a state of complete
physical, mental and social well-being and not
merely the absence of disease or infirmity’; and
in the WHO long-term vision for health in the
18.
rethink, now, on how we view progress and how we will build a
good future for coming generations.
I think the concept of the ‘doughnut economics’ GENETIC
makes sense: there is a scarcity of resources in many PREDISPOSITION
parts of the world that has to be addressed to lift TO ADRS
“What millions of people out of poverty, ill health and
does it take for unhappiness – but an increase in resources
consumed in some areas must be compensated
people to feel for by a decrease of resources used in others.
good, to be Real sustainable development can only be BETTER EVIDENCE FOR

sustainable development goals era to ‘ensure
healthy lives and promote well-being for all at all
happy?”
ages’.
To achieve these aspirational goals – in which
our work, of course, has a genuine contribution to
make – we cannot concentrate only on reducing the disease
burden; we need to also identify the factors that influence a
wider sense of well-being – what does it take for people to feel
good, to be happy? How does a community meet emotional and
spiritual needs, and how do we bring people together in a truly
cooperative and supportive spirit?
22.
achieved if there is a balanced system, not one
where the few profit from the many, but where
BETTER HEALTHCARE
we distribute the gains and losses more equitably,
and where we contribute as much to the overall
system as we take out. Those of us living in the more
affluent parts of the world must change our way of living –
now – otherwise we are heading towards a system collapse where, NEW
ultimately, we will all be losers, and happiness will be only a ERICE REPORT
memory. I know we can do better than that!

CELEBRATING BIRTHDAYS 26. 34.

POSTER
In trying to make sense of a complex reality, the happiness My granddaughter will be eight years old in a couple of weeks. WEB-RADR
REPORTING GALLERY
index, like all scoring systems, gives only an incomplete picture, She has spent hours thinking about her birthday celebration;
in this case of the key ingredients from which true happiness she has written a wish list and planned the party for her friends, APP
can be built, and felt. But it can serve an important purpose of and she is all starry-eyed when she talks about her special
stimulating a healthy discussion about well-being and happiness, day. She reminds me of the joy of birthdays and of the special
why it is denied to so many people in the world, and how we can ones that the WHO Programme and UMC

24.
change for the future. And importantly, the introduction of the will be celebrating in 2018, 50 years and
happiness index is, in my view, a much needed shift in focus 40 years respectively. UMC will have a
from financial targets as the main measure of progress. It’s easy big celebration in May; we are already
to get stuck on quantitative measures, when qualitative ones may planning for this and other activities and REPORT ILLICIT
really be the key – just as in the world of wise patient therapy. hope that many of our friends around the DRUG REACTIONS
There still seems to be the general supposition that economic world will be celebrating with us.
growth is a prerequisite for development, even in the UN
sustainable development goals – albeit referred to as ‘decent
work and economic growth’. Everywhere you turn nowadays
the term ‘sustainable development’ comes up; the concept is
laudable, and necessary – but how many of us really mean what 04. UPDATES
Pharmacovigilance news from Mexico; 14. NEW UMC ONLINE COURSES
Studying pharmacovigilance just got 30. SOCIAL
KUWAIT
MEDIA PROJECT IN

we say when we talk about sustainable development? At the WHODrug meeting in Chicago; New easier, with our new and free online In the absence of a national pharmaco-
vaccine nomenclature in WHODrug; course on signal detection and causality vigilance centre, Reem Al-Essa uses
simplest level, are we using and throwing away less paper and
VigiFlow updates; Ecuador joins the assessment. social media to raise drug safety
plastic in our daily lives? Marie Lindquist, Director
WHO Programme. awareness in Kuwait.

09. EDUCATION 23. OPINION: PATIENTS BEHIND

STATISTICS
32. IN BRIEF
SCOPE e-learning module on ADR A better culture of drug safety demands News from UMC and the world of
UPPSALA REPORTS Covering the world of pharmacovigilance reporting; UMC’s International greater appreciation for patient stories, pharmacovigilance.
Pharmacovigilance Training Course. says UMC medical doctor Rebecca
Editor-in-Chief Paula Alvarado. Editors Federica Santoro & Geoffrey Bowring. Editorial committee Supported by a team of multi­disciplinary
pharmacovigilance experts. Production UMC Global Communications. Design Daniel Hansson, Zellout, Sweden.
12. MINING TEXT FOR
Chandler.
35. INGIAMPAOLO
MEMORIAM:
VELO
Cover illustration Zellout.

Contact Uppsala Monitoring Centre, Box 1051, S-751 40 UPPSALA, SWEDEN | info@who-umc.org | +46-18 65 60 60. Web www.who-umc.org
DEDUPLICATION
A novel algorithm by the US FDA can 29. ADR REPORTING IN JAPAN
Centralised checkpoints in the Japa-
use information in case narrative texts nese hospital network are expected to
Social media UMCGlobalSafety company/Uppsala-Monitoring-Centre UppsalaMonitoringCentre c/UppsalaMonitoringCentre
to identify duplicate case reports. improve the quality of ADR reports.

2 U PPSA LA R EPORTS / ISSU E 77 I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 3
 Updates Updates
benefit from pharmacotherapy counselling,”
said Heloísa Conesa, pharmacovigilance
officer at UMC and one of the conference
speakers. “Patricia Mastroianni and Manuel
Machuca ran a workshop in which they
invited a patient to do his pharmacotherapy
counselling with the participants. It was a
great source of inspiration to see real-life
pharmacovigilance: how a patient reports
adverse events and the challenges in
collecting information for a report.”
This year’s AMFV conference ended
on an inspirational note, with special guest
Gabriel Najera, motivational speaker and
owner of the If I Can You Can corporation.
Drawing from his personal experience of
being born without arms, Mr Najera taught
the audience what medicines safety means
to people, and motivated everyone to keep
fighting for what they want, to build a

PHARMACOVIGILANCE
pharmacovigilance system that guarantees
patient safety.
AMFV believes that events like this
will allow pharmacovigilance professionals

PROFESSIONALS EXCHANGE
to keep developing, and create a better
culture of drug safety that will ensure safe
and rational use of medicines and medical

IDEAS IN MEXICO
devices in our societies.

Everardo Vazquez
Vice-President, AMFV Motivational speaker Gabriel Najera, here with AMFV vice-president Everardo Vazquez, ended the
evazquez@amfv.org.mx conference on an inspirational note.

In July 2017, 300 people gathered in the Mexican city of León, Guanajuato to
attend the annual conference of the Mexican Association of Pharmacovigilance.
S
INCE ITS FOUNDING in 2005, the
Mexican Association of
Pharmacovigilance (AMFV) has set
itself the goal of supporting the
national pharmacovigilance programme
coordinated by the Mexican drug regulatory
authority, Comisión Federal para la
Protección contra Riesgos Sanitarios
(COFEPRIS). It does so by engaging in
dissemination, promotion and training
activities aimed at healthcare professionals,
the pharmaceutical industry or society in
general, to establish pharmacovigilance as a
common practice in Mexico.
For the 2017 conference, AMFV joined
forces with the Mexican College of Hospital
Pharmacists to create a culture of what
pharmacovigilance and hospital pharmacy
mean today. Members of the association and
healthcare professionals with an interest in
pharmacovigilance were invited to share
knowledge on regulatory, academic and
industrial matters related to patient safety.
The agenda included presentations on
technovigilance – the safety of medical
devices – and on the rational use of
medications, with speakers of international
and national stature such as Dr Helgi
Jung from the National Autonomous
“It was interesting to see
how individuals from
different specialties can
interact, especially how
pharmacovigilance can
benefit from pharmaco-
therapy counselling.”
University of Mexico, Dr Gilberto
Castañeda from the Center for Research
and Advanced Studies of the National
Polytechnic Institute of Mexico, and Dr
Mariano Madurga, formerly at the Spanish
Agency for Medicines and Medical Devices.
Topics included generic versus innovative
medicines, the safety aspects of biosimilar
products, pharmaceutical care-related
issues, and the importance of correct
dispensing of medicines for patient safety.
OVER THREE DAYS, participants from
Mexico, Venezuela, Colombia and Europe
– many of them from hospital pharmacies
– shared pleasant experiences and discussed
challenges faced by healthcare professionals.
“It was interesting to see how individuals
from different specialties can interact,
especially how pharmacovigilance can
News from the Mexican national centre
Before attending the AMFV conference,
UMC pharmacovigilance officers Elki
Sollenbring and Heloísa Conesa visited
the Mexican national centre at
COFEPRIS.
There, they met local pharmaco-
vigilance experts and delivered pre-
sentations on the WHO Programme
for International Drug Monitoring,
reporting quality and signal detection.
The Latin American colleagues
shared their latest achievements and
the challenges they face in their daily
work. “It was important for us to meet
the national centre team members,
and interesting to learn more about their
work,” said Elki Sollenbring. “We made
some presentations that are relevant to the
work they do and shared experiences.”
Mexico has been a full member of the
WHO programme since 1999. Earlier this
year, they released a new ADR reporting
form based on the ICH E2B format for
electronic transmission of individual case
safety reports, and are now building a
new data management system based on
that format. “One of the centre’s priorities
now is to complete the development
of the data management system so
they can start implementing its use in
their daily activities,” Elki Sollenbring
said. “Another big achievement for the
Mexican centre has been the recent
introduction of Pharmacovigilance
Norm 220. They had been working on
the document since 2015, and it was
finally launched in June 2017.” The
new law is expected to align Mexican
pharmacovigilance activities to global
standards. 

4 U PPSA LA R EPORTS / ISSU E 77 I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 5
 Updates Updates

Increased granularity of vaccine

substances in WHODrug
Vaccine substances have historically
been included in WHODrug with a very
simple nomenclature structure: the
disease or pathogen name, followed by
the word ‘vaccine’. A new, more granular
structure now allows for better identifi-
cation.
Both the UMC signal analysis team
and external WHODrug users had raised
concerns about the insufficient level of
detail in which vaccine substances were
described in WHODrug. The lack of
detailed information resulted in ambiguity
of interest (e.g. strains or conjugated
antigens/toxoids).
A great advantage of the new structure is
that it enables more precise signal detection
for vaccine products. “The increased
granularity of vaccines in WHODrug will
allow for more fine-tuned signal detection.
We will be able to focus on safety issues
that may be related to excipients, adjuvants
or other ingredients, not just the micro-
organisms against which the vaccines are
directed,” says Rebecca Chandler, medical
doctor and vaccine specialist in the UMC
In the new structure, all vaccine
subtypes for the same disease or pathogen
are linked together using the WHODrug
Drug Code logic, which allows each
WHODrug user to customise the level
of detail to fit their analysis. The new
structure for vaccine substances is available
from the March 2017 release of WHODrug
and onwards.
Damon Fahimi
Product Specialist, UMC
damon.fahimi@who-umc.org

WHODrug users share

and confusion, and made it difficult to Research team. @DamonFahimi
distinguish between different vaccine

coding expertise in Chicago

subtypes developed for the same disease
or pathogen. Spurred by such comments,
in the autumn of 2016 UMC initiated a
project to restructure and rename these
VIVOTIF VIVOTIF
After Bangalore and Mumbai in India and Glasgow in Scotland, substances.
The new and standardised structure March
the next stop on the WHODrug User Group Meeting tour this year still allows for easy identification of the
disease or pathogen that the vaccine is 2017
was the “Windy City” of Chicago, US.

Ty

Va

Ty

Va

Li

Ty
meant to protect from. However, the old

ve

ra

21
p

p
c

c
ci

ci
ho

ho

a
ne

ne
nomenclature is now followed by additional

id

T
HE EVENT WAS HELD in June,
at the same time as the Swedish
Midsummer holiday. So as the
rest of the UMC staff were getting
ready to feast on pickled herring and dance
around the maypole, the WHODrug team
B3 and C3 formats, announced the
launch of the WHODrug Change Request
Tool, and collected input from the user
community for upcoming best practices on
using Umbrella Records in WHODrug.
Chen from ThesIS, which was appreciated
by many. “I really liked the audience
engagement during the expert panel
discussions. I am sure both experts and
new members learned something new
that will help them with daily coding
id
details, which specify the type of vaccine
(e.g. live attenuated or recombinant), its
specific properties (e.g. oral or intradermal
administration route) and other properties An example of how increased granularity affected the trade name Vivotif in WHODrug.

Meet the new VigiFlow

experienced a rather unusual yet pleasant
way to celebrate the summer solstice – with
pink cotton candy and in-depth discussions
on the WHODrug portfolio.
Since the early 2000s, WHODrug User
Group Meetings have been conducted
regularly all around the world. The
events, hosted by UMC, aim to facilitate
and harmonise WHODrug usage. The
meetings are also an opportunity for users
to give feedback to the WHODrug team at
UMC and influence future developments.
The topics for the User Group Meetings
are decided by a programme committee
consisting of volunteers from the user
community and representatives from UMC.
As is customary, the first part of the
full-day meeting, held at the Hard Rock
Hotel in Chicago, was devoted to UMC
updates on WHODrug-related news. The
UMC team presented the newly introduced
THE MEETING CONTINUED with an
interactive coding workshop; after
lunch, there followed a presentation on
Customised Drug Groupings and using
the WHODrug Insight browsing tool,
given by experienced WHODrug user
Hank Dennis from Chiltern International.
“I highly recommend attending the
WHODrug User Group Meetings,” Dennis
commented after the meeting. “There is
plenty of new information every year as
the dictionary terminology is evolving. It
helps to understand the updates, to see how
other companies in your industry are doing
things, and to collaborate and network with
colleagues. Many times these collaborative
efforts lead to discussions that result in new
processes or efficiencies.”
The meeting ended with an engaging
panel discussion session with experienced
WHODrug users, moderated by Henry
challenges,” Lubomir Tarabcak from
Actelion Pharmaceuticals remarked.
“The UMC team has shown once again
that these meetings can be very educative,
interactive and well-organized.”
Since the Chicago meeting, User Group
events have also been conducted in Beijing,
China, Gaithersburg, US and Tokyo, Japan.
Damon Fahimi
Product Specialist, UMC
damon.fahimi@who-umc.org
@DamonFahimi
For more information:
WHODrug@who-umc.org
www.who-umc.org/whodrug/
user-group-meetings
A new version of VigiFlow, the data
management system used by pharmaco-
vigilance centres as their national
database to record, process and share
reports of adverse effects, was released
in October 2017.
The new version supports the workflow
around manual case intake, structuring of
ADR case report data and recording of
causality assessment results, with options
for WHO-UMC causality, WHO AEFI
causality and Naranjo methods. Additional
features will be developed and implemented
throughout 2017 and 2018. The system
has also been updated to comply with the
ICH E2B(R3) format, the latest interna-
tional standard for electronic transmission
of individual case safety reports.
To help national centres in the detection national centre to set up a timetable to
of safety issues, VigiFlow users can start using the new version, based on the
access VigiLyze – the UMC’s advanced features and languages in use at the time.
search and analysis tool – to compare and The goal is to have all VigiFlow users
supplement their national data with the upgraded by the end of 2018.
accumulated global VigiBase data, from
all members of the WHO Programme for
International Drug Monitoring.
The Medical Dictionary for Regulatory
Activities (MedDRA) is the default medical Monica Plöen
terminology implemented in the new Product Manager, UMC
VigiFlow. Countries currently using WHO monica.ploen@who-umc.org
Adverse Reaction Terminology (WHO-ART)
will be contacted by UMC to receive help
in converting their data to MedDRA.
For more information:
VigiFlow is used in more than 70 contact UMC at vigibase@who-umc.org
countries, and the updates will be rolled
out gradually. UMC will contact each

6 U PPSA LA R EPORTS / ISSU E 77 I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 7
 Updates
Ecuador gears up for pharmacovigilance
The World Health Organization recently confirmed Ecuador as the 126th member of the
WHO Programme for International Drug Monitoring. This is an important achievement
for the country, in terms of the latest thinking in the science of pharmacovigilance to which
it will have access, and benefits to the health of the Ecuadorian population.
M S
ULTIPLE EFFORTS have been
made in recent years to develop
pharmacovigilance practices
in Ecuador. In 2011, the
‘Regulation for the operation of the
National Pharmacovigilance System’
was issued, and the following year saw
the establishment of a national health
regulatory agency (Agencia Nacional de
Regulación, Control y Vigilancia Sanitaria,
ARCSA) to implement the new law. In
2015, ARCSA initiated a pilot plan to put
the pharmacovigilance programme into
operation in 62 health institutions in the
country, with a focus on providing training
in the detection and reporting of adverse
drug reactions.
To date, the agency has trained
more than 20,000 health professionals
throughout Ecuador, and the national
pharmacovigilance office (Centro Nacional
de Farmacovigilancia, CNF) currently has
22 technicians who develop management
and training throughout the country.
Thanks to these efforts, 6,575 reports
8 U PPSA LA R EPORTS / ISSU E 77
of suspected adverse events have been
received since 2015, with an increase of
36% between 2015 and 2016. Of all these
reports, 38% are serious adverse events,
which underlines the importance of putting
good pharmacovigilance practices in place
in Ecuador.
“Ecuador is a country with over 16
million inhabitants, and it is important to
include pharmacovigilance in their health-
care activities,” commented Elki Sollenbring,
UMC pharmacovigilance officer with a
focus on Latin American countries.  Pharmacovigilance in Europe (SCOPE) Joint
“Ecuador have already established a system
that will benefit the population, they have
the capacity to share the information they
collect with VigiBase, and now they will
also take advantage of all the benefits that
member countries of the Programme have.”
The main challenge now is to obtain
greater commitment and participation of
health professionals in the generation of
reports, by positioning them as key players
in this work that protects the health of
Ecuadorians.
Bringing European doctors
up to speed on ADR reporting
Doctors across the EU can now learn more about the importance
of reporting adverse drug reactions via a free e-learning module.
USPECTED ADVERSE DRUG REACTION
Lisandra Garcia Hechavarría (ADR) reports form the cornerstone
Pharmaceutical Chemist, National of pharmacovigilance systems and act
Pharmacovigilance Centre Ecuador as early warning signs to help monitor
lisandra.garcia@controlsanitario.gob.ec the safety of medicines and safeguard
patients from preventable side effects. A
Elena Galarza Figueroa new e-learning module developed by the
Pharmaceutical Chemist, National UK’s Medicines and Healthcare products
Pharmacovigilance Centre Ecuador
Regulatory Agency (MHRA) aims to educate
margarita.galarza@controlsanitario.gob.ec
healthcare professionals on the importance of
reporting.
The module was developed through the
Strengthening Collaborations to Operate
Action project, and builds upon the success
of the first EU-wide social media campaign
to raise awareness of ADR reporting. An
initial SCOPE survey found that many
European countries lacked educational
materials on ADR reporting. By the end of
the 45-minute module, learners should:
•u  nderstand that by reporting they play a
vital role in pharmacovigilance, and that it
is their professional duty to report
•k  now where to report an ADR and what
happens once a report is submitted
Photo: Getty Images.
• learn about the types of ADRs, including
situations that should trigger a report,
and the importance of reporting ADRs in
children
• k now who can complete and what to include
in a report
• find up-to-date information on ADRs
•b  e able to answer patients’ questions about
ADRs and explain how they can also report.
THE EUROPEAN ACCREDITATION COUNCIL
for Continuing Medical Education
(EACCME), part of the European Union of
Medical Specialists (UEMS), has given the
module the highest order of accreditation.
This means that doctors are awarded 1
EACCME credit – equivalent to 1 hour
of Continuing Professional Development
(CPD) or Continuing Medical Education
I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M
(CME) – upon completion of the module,
and more credits can be claimed if more
time is spent on it. This is expected to act
as an incentive to undertake the e-learning
package.
The module is free, easy to use and
interactive. It combines traditional
evidence-based review with problem-
oriented learning to encourage reflection,
and case scenarios help learn from practical
clinical situations. Learners receive tailored
feedback on answers to problem-based
questions so they remain engaged with the
material and gain a fuller understanding of
why their answer was right or wrong. The
e-learning is also designed to help learners
fit the module into their busy schedules.
Doctors can learn at their own pace and
pick up where they left off, as long as the
same device is used to access the module.
Upon completion, learners are asked to fill
out a short survey and are rewarded with a
downloadable certificate.
Many medicines regulators in Europe
have acted quickly to encourage use of the
module. Alongside MHRA, authorities in
Croatia, Ireland, Italy, Latvia, Lithuania
and Romania announced the module’s
launch via national press releases. Some
Education
Photo: Shutterstock.
also encouraged uptake by doctors via social
media and other channels. The e-learning
package could be adapted for use elsewhere
and translated into other languages. Current
membership of UEMS includes 37 countries
and EACCME accreditation includes
mutual recognition by the American
Medical Association and other medical
specialties outside the EU.
The authors hope that the e-learning will
empower healthcare professionals to report
ADRs, and that ADR reporting becomes
part of a positive medicines safety culture
that is embedded deeper into the healthcare
system.
Mitulsinh Jadeja
Special Projects Manager, Vigilance Intel-
ligence & Research Group, Medicines and
Healthcare products Regulatory Agency
(MHRA)
mitul.jadeja@mhra.gov.uk
@MHRAgovuk
www.scopejointaction.eu/outputsandresults/
READ
MOR E: adr-collection/awareness-levels/story.html
Mitul Jadeja, “ADR reporting awareness on
social media”, Uppsala Reports 75.
ISSU E 77 / U PPSA LA R EPORTS 9
 Education
“In 2016 we conducted
a workshop on
pharmacovigilance
and drug safety to
upgrade the knowledge
of traditional medicine
practitioners, Ayurveda
doctors, interns and
other interested groups.
There were around 110 participants and
it was led to develop a pharmacovigilance
reporting system among traditional
practitioners. I also shared the learning
materials from the Uppsala course within
the Ayurveda medicine curriculum for
students at the Institute of Indigenous
Medicine at the University of Colombo.
This is a positive step taken by the
Department of Ayurveda Pharmacology
and Pharmaceutics to promote the safe use
of traditional medicines in Sri Lanka.”
Pathirage Kamal Perera,
University of Colombo, Sri Lanka
“The course helped us
in the assessment of
signals and safety issues,
to determine what risk
minimisation measures
to take and how to
communicate risk
effectively. Previously, our risk
communication used traditional channels:
letters, bulletins, posters, pamphlets and
press statements. We are now moving
towards social media and more attractive
ways to share information with the public
and bring their attention to medication
safety. The slides provided at the end of
the course were used for echo-training
sessions for staff, with a focus on signal
evaluation and communication. We also
gave a number of trainings and talks
for healthcare professionals in private
facilities, gathering over 600 participants,
and we introduced an ADR reporting
form for consumers: the Consumer Side
Effect Reporting Form (ConSERF).”
Noraisyah Mohd Sani, National
Pharmaceutical Regulatory Agency
(NPRA), Malaysia
10 U PPSA LA R EPORTS / ISSU E 77
TURNING KNOWLEDGE
INTO ACTION
Every spring, Uppsala Monitoring Centre
welcomes around 30 participants from around
the world to its popular pharmacovigilance course
in Uppsala. Nine months later, we invite them
to share their latest achievements with us, and
to reflect on how their work has changed since
attending the course. This is what some of the
2016 participants had to say.
I NSPIR E. ENGAGE. TR A NSFOR M
Education
“Since the course, I have
been using VigiLyze to
search for ADR reports
more often. I recommended it to
my boss to calculate the number of specific
ADR reports in the world, and he used it
too. My main achievement though has been
the advancement of our pharmacovigilance
training in Japan. After I participated in
the course, I proposed many things to
improve our training; we started using self-
introduction sheets for each participant, and
arranging desks to promote discussions. I
made trainings for colleagues, regulators
from overseas, healthcare professionals and
medical students.”
Yu Wada, Pharmaceuticals and
Medical Devices Agency (PMDA),
Japan
“Our main achievement
has been receiving full
membership in the WHO
Programme, after being
associate members since
2011. As Maldives is just starting its work
in ADR reporting, every aspect covered
in the course was relevant and useful:
understanding the ICSR tool, how to do
data mining, and causality assessment.
Some awareness sessions on patient safety
and adverse event reporting have been
carried out with prescribers and nurses to
improve the number of reports. Since the
training, we have also started entering data
into VigiFlow.”
Photos: Gediminas Norgèla and Göran Ekeberg for UMC.
Aminath Moomina Moomina,
Maldives Food and Drug Authority,
Maldives
Interested?
The 20th International
Pharmacovigilance Training course
will be held from 21 May to 1 June
2018. You can apply on the UMC
website until 12 January 2018:
www.who-umc.org/education-training
I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77
75 / U PPSA LA R EPORTS 11
 Research
Text is key for eliminating
duplicate reports
Duplicate case reports are an obstacle to effective pharmaco-
vigilance but identifying them is a difficult and laborious task.
The US Food and Drug Administration recently developed a
deduplication algorithm that – unlike previous methods – can
utilise information from the free text of case narratives.
S
PONTANEOUS REPORTING
systems are one of the best
means of detecting rare
adverse effects related to the
use of medical products. The
US Food and Drug
Administration (FDA)
monitors product safety
issues in part by employing an automated
tool to flag product-adverse effect pairs that
are reported more commonly together than
expected. This method may report a false
12 U PPSA LA R EPORTS / ISSU E 77
association if there are duplicates of some
cases in the data. Even a handful of
duplicates can appear as a surge in reporting
that triggers an alert and requires time and
manual investigation to debunk.
Duplicate cases can arrive in reporting
systems in several ways, but often arise as
a side effect of mandatory reporting rules
intended to enhance safety. Manufacturers
must submit case reports involving their
products to the FDA. However, each
manufacturer may submit their own
independent report for the same patient if
that patient was exposed to multiple medical
products, thus increasing the chances of
duplicates ending up in the system. Without
an efficient means of filtering these duplicate
cases, performing accurate aggregate case
analyses requires significant manual effort.
Along with our reviewer colleagues, we
recently published the details and evaluation
results of an algorithm, now incorporated
into our Decision Support Environment
platform, that was designed to assist FDA
medical reviewers and epidemiologists in
quickly identifying duplicate cases. The
algorithm is based on the probabilistic
Fellegi-Sunter model of record linkage,
which compares two records on a number
of fields and attempts to determine the
likelihood that they describe the same
incident.
I NSPIR E. ENGAGE. TR A NSFOR M
T Our Head of
HE MOST NOVEL ASPECT of the
algorithm was the use of free text
from case report narratives. Previous
efforts have focused mainly on
structured information – like age, gender
and location – that is provided by reporters,
since narrative text is harder to obtain and
process. We applied a clinical Natural
Language Processing (NLP) system with
demonstrated performance on adverse event
reports to extract certain clinical features,
like symptoms, diagnoses and treatments,
from the text for comparison.
The probabilistic approach to record
linkage has been shown to be more effective
than a deterministic one, in which a subset
of fields must all match exactly, so it is
unsurprising that other tools have been
based on the Fellegi-Sunter model as well,
including the vigiMatch method employed
in WHO’s VigiBase system. Some have
also incorporated features that have not
(yet) been included in our algorithm,
like vigiMatch’s ability to assign a higher
‘weight’ score to matches on rarely reported
values (e.g. Country=‘Montenegro’,
with only about 800 reports in the entire
database) than to matches on commonly
reported values (e.g. Country=‘Germany’,
with over 500,000 reports). Enhancements
like these will undoubtedly lead to
improvement in our model, but the greatest
growth potential resides in properly
capturing the information from narratives
to allow automated expert-level comparison
between case reports.
A
LTHOUGH THE INCLUSION of features
from the case narrative text did not
generally improve the automated
classification performance of our
algorithm in this particular study, we remain
confident that narratives provide valuable
benefits. We have twice demonstrated that a
deduplication algorithm utilizing free text
can return high-quality candidate lists of
potential duplicate cases for expert review.
One was in this study, where we found that
11 of the 14 highest ranked pairs in a data
set were true duplicates (with the 4 other
true duplicates ranked at lower levels). The
other instance was an experiment that was a
precursor to that work, in which we used
only textual information and patient sex to
identify a set of 53 clusters of 2-4 reports
that appeared to be duplicated; subsequent
expert review confirmed 49 of them.
Further, narratives contain a considerable
amount of information that may be missing
I NSPIR E. ENGAGE. TR A NSFOR M
Duplicate Cases
Two or more records describing the same
occurrence of events – same adverse effect(s)
experienced with the same medical product
at the same time – for the same patient. Due
to reporting inaccuracies, two records can
be considered duplicates even if they do not
contain an identical list of events.
Decision Support Environment
An interactive software platform providing
data and analytical tools to medical experts
to facilitate decision-making.
Clinical Natural Language Processing
The automated processing of unstructured,
human-written textual information from a
clinical/medical setting to provide useful
insight or analysis.
from structured fields, because it is either
not recorded in the appropriate place(s)
or not feasible to encode at all. The latter
may include facets like medical or family
history, or temporal information about the
progression of symptoms. We will continue
to refine the NLP tool for capturing this
information because unlocking the potential
of free text narratives will benefit a litany of
public health and clinical data issues, not
just deduplication.
Our comments are an informal communi-
cation and represent our own best judgment.
These comments do not bind or obligate FDA.
Kory Kreimeyer
ORISE Fellow, Office of Biostatistics
and Epidemiology, Center for Biologics
Evaluation and Research, US Food and
Drug Administration
kory.kreimeyer@fda.hhs.gov
Richard A. Forshee
Associate Director for Research, Office
of Biostatistics and Epidemiology, Cen-
ter for Biologics Evaluation and Research,
US Food and Drug Administration
richard.forshee@fda.hhs.gov
Taxiarchis Botsis
Visiting Scientist, Office of Biostatistics
and Epidemiology, Center for Biologics
Evaluation and Research, US Food and
Drug Administration
taxiarchis.botsis@fda.hhs.gov
Kreimeyer K et al, “Using probabilistic
READ record linkage of structured and
MOR E:
unstructured data to identify duplicate
cases in spontaneous adverse event
reporting systems”, Drug Safety, 2017.
Research
Research says…
UMC’s Chief Science Officer Niklas
Norén has a long-standing interest
in duplicate detection. In a commen-
tary published in Drug Safety last
May, he reflected on the value of
the FDA study for deduplication
efforts worldwide. We asked him
to share his thoughts with Uppsala
Reports readers.
What do you find most inspiring about this
research?
The authors’ ambition to break new ground.
Although the study did not show an improvement
in duplicate detection with the use of free text,
the potential is there. I am grateful to the authors
for sharing their results at an early stage, so that
the rest of us can build on their ideas in our own
research.
How will this research impact UMC’s efforts to
improve duplicate detection in VigiBase?
The vigiMatch method provides a solid base for
deduplication, but it is by no means a definitive
solution. In principle, vigiMatch can handle both
features extracted from free text – such as the
identified age of a patient – and the actual words
as input. For direct text matching, the challenge
is computational – how do we scale this to the
millions of reports in VigiBase? If each pair of texts
takes more than a few microseconds to compare,
then it will not be computationally feasible to
use such text matching algorithms for VigiBase,
because in principle we have 15 million squared
pairwise comparisons to make! 
How important is the ability to mine free text?
Case narratives provide a wealth of clinical
information, and we’ve been developing a number
of natural language processing methods to mine
free text. We can extract severity information
from VigiBase narratives and analyse literature
references to flag known adverse effects. We are
also beginning to make headway in the removal
of sensitive data from free text, and the mining of
social media for possible adverse drug reactions.
As you see, the value of free text extends
far beyond duplicate detection.
READ
MOR E:
Norén GN et al, “The power
of the case narrative - can
it be brought to bear on
duplicate detection?”,
Drug Safety, 2017.
ISSU E 77 / U PPSA LA R EPORTS 13
 Education
Pharmacovigilance
training at your fingertips
With the launch of its own distance learning platform, UMC now offers
an even more diverse range of education and training to meet the needs of
pharmacovigilance professionals. The first online course on signal detection
and causality assessment is now freely available and open for registration.
T
HERE IS A GREAT NEED for
training in pharmacovigilance
and for many years UMC has
taken a variety of approaches to
support pharmacovigilance
professionals around the world.
The popular annual course in Uppsala will
be held for the twentieth time in 2018 and
UMC staff travel regularly to member
countries of the WHO Programme for
International Drug Monitoring, to engage in
training activities and conferences on site.
To complement such face-to-face training,
UMC has launched a distance learning
platform to reach out to even more people
than before.
The first online course deals with signal
detection and causality assessment, topics
frequently requested by pharmacovigilance
centre staff. The course was developed using
the microlearning approach, which offers
bite-sized ‘nuggets’ of information that can
“Our microlearning
approach makes
training accessible
even to people with
very busy schedules.
Now anyone can learn
pharmacovigilance!”
14 U PPSA LA R EPORTS / ISSU E 77
be easily absorbed and revisited. The course
is divided into modules, which are subdivided
into lessons. Each lesson is concise and
related to a clear learning objective.
Transcripts are available to help those
who may find the spoken English difficult to
follow, and they can also be used to review
the contents quickly without having to replay
the video. By taking a test at the end of each
module, students can check whether they
understood the material and keep track of
their progress. The first four course modules
were launched in October, while a fifth
module will be released in 2018.
THE ADVANTAGE of the online course is its
flexibility – it can be studied anytime,
anywhere and at any pace. “Distance
learning is perfect for anyone who may not
be able to travel to a training session,” says
Johan Ellenius, team manager in UMC’s
Research department. “Our microlearning
approach makes training accessible even to
people with very busy schedules. Now
anyone can learn pharmacovigilance!”
The material is entirely free, so all the
student needs is a computer, a tablet or a
mobile phone connected to the internet. The
platform will be of special value to
pharmacovigilance professionals who are
unable to attend UMC’s live training, but it
can also be used to brush up on specific
topics after attending a live event. An added
Education
ACCESS THE COURSE:
HTTPS://COURSES.
4 90
WHO-UMC.ORG/
REGISTRATION/SDCA
MODULES
MINUTES OF VIDEO
2,280
27
REGISTRATIONS
benefit of the distance learning approach is
that by reducing travelling, it will save time,
65,000
money and the environment.
So far, audience response has exceeded
expectations – over 1,500 people signed up
for the course within a month of its launch, LESSONS
and numbers are increasing steadily. The
project is in its pilot phase now and its
usability, relevance and impact will be PEOPLE REACHED
evaluated to decide if more courses should ON SOCIAL MEDIA
be added. For that, UMC relies on your
participation and valuable feedback. If you
know somebody who would be interested in
helping us by undertaking the course, do
spread the word. We hope that many
pharmacovigilance professionals will
complete the course and give us their
feedback. The lessons were designed with
pharmacovigilance centre staff in mind,
especially new signal assessors, but they are
freely available to anyone with an interest in
the topic.
Ruth Savage, medical
Anna Hegerius advisor to UMC, explains
Senior Specialist,
Education and Training, UMC
causality assessment
in the second course
anna.hegerius@who-umc.org module.
Access the course:
https://courses.who-umc.org/registration/sdca
I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 15
 Research Research

HUNTING for GENETIC

PREDISPOSITION to
ADVERSE DRUG
REACTIONS
P
How can potential individual-level risk RECISION MEDICINE IS most often
considered in the context of using genetic
enthusiastically discussing our question, was truly
inspirational,” Lovisa Sandberg said. “It helped us
factors for adverse drug reactions, identified diversity to predict which patients are
more likely to respond favourably to
understand where research in this area is at today, where
the challenges are and that international collaborations
in anonymous spontaneous reports, be medicines. However, it can also be used to
predict which patients are more likely to
are essential.”
Dr Mia Wadelius, professor in clinical
tested in a clinical setting? This was respond unfavourably - in other words, to present
adverse drug reactions (ADRs). Identifying individual
pharmacogenomics at Uppsala University and scientific
director of Swedegene, was among those who joined the
the question raised by UMC staff at differences in genes, environment and lifestyle could
explain why some people experience rare ADRs, while
discussion. Swedegene is a national biobank and
phenotype resource centre for ADRs, located at Uppsala
the AIMday Precision Medicine others do not. Given the relevance of precision medicine
to pharmacovigilance, it was fitting of UMC staff to take
University Hospital and Uppsala University. The centre
collaborates with the Swedish Medical Products Agency
meeting held in Uppsala last June. part in this year’s AIMday discussions.
The AIMday concept was developed by Uppsala
and has ethical approval to collect information from
individuals who experience adverse reactions to
University Innovation in 2008, and has since been held medicines. In order to detect genetic risk factors for
at Uppsala University several times a year. Organisations well-characterized ADRs, the patients’ DNA is collected
define the programme of the meeting by raising and sequenced to enable genome-wide association
questions they would like to discuss with academic studies. Unfortunately, it is difficult to find enough cases
researchers for an hour. The session starts with a brief of rare serious reactions within one country alone.
presentation of the background to the question, followed Multi-national data is most likely needed to explore
by discussions on the topic where knowledge is genetic risk factors for rare ADRs, and this is an area
exchanged and new perspectives are raised. The that would require further research and evaluation.
purpose of the discussion is not necessarily to come up What the member countries of the WHO Programme
with solutions to the issue at hand, but to allow for International Drug Monitoring and the UMC might
organisations and researchers to connect and explore contribute to such scientific development remains an
further collaboration options to answer the question. open question.

F
IVE ACADEMIC SCIENTISTS participated in the
discussion led by Rebecca Chandler, Lovisa
Sandberg and Kristina Star from the UMC Kristina Star

Photo: Getty Images.

Research department. As a background to the question Team Manager/Researcher, UMC
raised, UMC staff gave examples of published safety kristina.star@who-umc.org
signals where further exploration to determine
READ www.aimday.se
individual-level risks would be desirable. “The short MOR E: www.swedegene.se
face-to-face session with researchers in the field, all

16 U PPSA LA R EPORTS / ISSU E 77 I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 17
 Feature
CAMPAIGN FOR
RADICAL REFORM
AND RE-FOCUS
IN CLINICAL RESEARCH
Better healthcare requires solid scientific evidence, high-quality research and
increased patient involvement at all stages of decision-making. Such were
the overarching conclusions of the Evidence Live meeting, which took place in
Oxford, UK last June. UMC staff in attendance share notes and impressions.
The story
EVIDENCE LIVE IS the annual meeting of a
radical movement for the reform of medical
research and publication, the involvement
of patients at the heart of research, and the
provision of useful, evidence-based infor-
mation for patients and clinicians to support
genuine shared decision-making. It is led
jointly by the Centre for Evidence-Based
Medicine (CEBM) at Oxford University,
UK, and the British Medical Journal (BMJ).
It is driven by members of an energetic
international community, including aca-
demics, clinicians, researchers, patients,
journalists and a host of representatives of
organisations in the public and voluntary
sectors. UMC people have contributed for
the last three years.
18 U PPSA LA R EPORTS / ISSU E 77
The 2017 conference
in Oxford
THE MEETING WAS, as usual, characterized
by commitment, passion, anger, optimism –
and evidence. There was plenty of evidence
of how degraded medical research and sci-
entific publications have become, revealed
through multiple examples of meticulous
work that showed just how shoddy much
research is (85% wasted projects, bad trials,
absent data, irrelevant outcomes, conflicts
of interest, and so on; 95% of submissions
are rejected by the BMJ). There were also
many contributions exploring strategies for
reforming clinical trials; for generating good
evidence, relevant to patients’ concerns; for
expanding the kind of evidence we consider
I NSPIR E. ENGAGE. TR A NSFOR M
to include individual patient testimony; for
improving clinical guidelines and practice;
for involving patients in every stage of
research, including formulating research
questions; for bringing good evidence
directly into shared decision-making in
clinical practice. The importance of the
evidence of (neglected) patient narratives
was promoted by several speakers, along
with the need to broaden our thinking on
the strength of evidence and its fitness for
purpose.
There were domain stars – Ben Goldacre,
Sir Muir Gray, Doug Altman – and an
inspiring list of bright, thoughtful and
stimulating others from all over the
world. UMC was represented by Director
Marie Lindquist, who gave an impressive
performance as the closing keynote speaker,
arguing for social and economic policies
Daniele Sartori comments:
EVIDENCE LIVE WAS a different experience
than your usual conference. It went beyond
the model of speakers delivering notions
to an audience, and truly engaged them
in two-way communication. The meeting
spoke loud and clear: stop doing research
Rebecca Chandler comments:
THIS CONFERENCE SIGNIFIED the start of a
paradigm shift in the way we collect, inter-
pret and implement evidence in the clinical
care of patients. The traditional paradigm
has been built on randomized controlled
trials which measure the effects for the
‘average’ and on the assumption of a more
or less paternalistic doctor-patient relation-
ship. The value of data from other sources
and in other forms is being recognized for
its potential to inform us about heteroge-
neity within the patient population and to
support a genuine shared decision-making
The manifesto
THE MOVEMENT has produced the basis of an evolving consultation, in the form of an edi-
torial published in the BMJ last June. Contributions are invited from all interested parties,
including patients and the public. The arguments for radical reform and the Manifesto’s
current proposals can be found on the BMJ website.
I NSPIR E. ENGAGE. TR A NSFOR M
Feature
across the world that would bring about
the positive well-being of humanity
beyond the mere absence of disease.
Bruce Hugman, communications
consultant for UMC, delivered
a vivid account of the threats
to evidence in the ‘post-truth’
era of ‘alternative facts’ and
offered some suggestions
for strategies to tackle the
contemporary degradation
of discourse. Other UMC
attendees included
Rebecca Chandler,
Ralph Edwards and
Daniele Sartori, who all
played a part as active
members of workshops
and other sessions.
Conference participants (Evidence Live Oxford); Blavatnik School of Government (Howard Stanbury).
“The meeting spoke loud
and clear: stop doing re-
that is not a priority for patients, stop putting
out fake evidence and start making it trans- search that is not a priority
parent. Patients and their rights and needs
were at the centre of the conference, which
for patients, stop putting
recognized that, so far, shared decision- out fake evidence and start
making has been only a partial success. making it transparent.”
model. I left the meeting feeling enthusiastic
and hopeful, as I felt that the new paradigm Bruce Hugman
means that the data collected in pharmaco- Communications Consultant, UMC
vigilance systems may come to be more fully brucehugman@hotmail.com
appreciated. Individual case safety reports
of suspected adverse effects are a perfect Rebecca Chandler
example of data which reflect true clinical Medical Doctor, UMC
rebecca.chandler@who-umc.org
outcomes directly reported from health-
@RebeccaChandle1
care providers and patients. I am very keen
to explore if VigiBase data can be useful,
Daniele Sartori
beyond causality assessment, for those more
Research Pharmacist, UMC
directly involved in clinical decision making. daniele.sartori@who-umc.org
Heneghan C et al, “Evidence based
READ medicine manifesto for better health-
MOR E:
care: A response to systematic bias,
wastage, error and fraud in research
underpinning patient care”, BMJ, 2017.
YouTube: Evidence Live 2017 playlist
Twitter: #EvidenceLive
www.cebm.net
ISSU E 77 / U PPSA LA R EPORTS 19
 Feature Feature

Restoring confidence T
HE DISTURBING DISCOVERY that
only about one third of the UK “Implementation of the recommendations
would have a radical effect on how research is

in evidence: UK report
population trusted medical evidence
and that two-thirds relied on the
opinions of friends and family as their
conducted, how evidence is communicated, and
preferred sources of information, runs how well patients and their health professionals
are supported in making the best decisions about

calls for big changes

through a major new report by the UK
Academy of Medical Sciences. Recent
controversies around the benefits and harms
of treatments such as statins, hormone
replacement therapy and Tamiflu also
highlighted the need for action.
“Enhancing the use of scientific evidence
A recent report by the UK Academy of Medical Sciences recommends to judge the potential benefits and harms
of medicines” was published in June this
major changes in how medical research is managed and communicated, year. It is the result of ‘a project to examine
how the generation, trustworthiness and
and includes proposals to ensure that good scientific evidence underlies communication of scientific evidence can be
enhanced to strengthen its role in decisions
every decision we take about medicines. by patients, carers, healthcare professionals
and others about the benefits and harms of
medicines.’ These are some of the headline
proposals to address real and perceived
weaknesses in medical research, evidence
and their communication:
Illustrations: The Academy of Medical Sciences.
medicines.”
• Involvement of patients, carers and the reforms being proposed, but it is clear that
wider public in research implementation of the recommendations
• Enhanced training in research methods would have a radical effect on how
and use of statistics research is conducted, how evidence is
• Support for new study designs and new communicated, and how well patients and
methodologies, such as health apps and their health professionals are supported in
wearable technologies making the best decisions about medicines.
• T he provision of evidence that is The presentation of the report and its
accessible, assessable and usable by the accompanying materials are also fine
intended audience examples of good communication practice
• Frameworks in which researchers can in action.
declare and manage interests
• Presentation of scientific evidence in a
clear, accessible and usable way
• Improvements in patient information
leaflets to include a balanced and easily
understandable appraisal of medicines
• A ‘traffic light’ system for press releases
indicating how likely the research is to
improve clinical practice in the near future
and the robustness of the research
• Codes of practice for all generators and
communicators of research evidence to
convey accurate, assessable and balanced
information to the public.

THERE IS ALSO a proposal that a single,

reliable, high profile, go-to destination
for clear, up-to-date and evidence-based
information should be strongly promoted;
in the UK, this would be the NHS Choices
website.
Among the excellent materials
accompanying the report are 90-second
videos illustrating the main points, social
media posts and beautifully designed
short summary documents of major
recommendations, including one that lists
questions patients should ask their doctors
when discussing their medicines, and an
accessible 8-page summary version of the
long and complex report.
A short summary like this does not
do justice to the depth and significance
of the issues being addressed, nor the
Bruce Hugman
Communications Consultant, UMC
brucehugman@hotmail.com
The Academy of Medical Sciences,
READ
MOR E: “Enhancing the use of scientific evidence
to judge the potential benefits and harms
of medicines”, 2017 (full report).
The Academy of Medical Sciences,
“How can we make better decisions about
medicines?”, 2017 (report summary).
acmedsci.ac.uk/policy/how-can-we-
all-best-use-evidence

20 U PPSA LA R EPORTS / ISSU E 77 I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 21
 Updates
New thoughts on the safety
of medicines from Erice
Twenty years after the first Erice Declaration, a new report calls for an update
of pharmacovigilance practices to be fit for purpose in the 21st century.
T
HE 1997 “Erice Declaration on
Communicating Drug Safety
Information” had a major and
lasting impact on thinking and
practice in pharmacovigilance
and patient safety communication.
It promoted the importance of dynamic,
ethical and transparent communication in
all matters relating to the safety of
medicines, and has been widely recognized
as a public health landmark.
Two decades after its publication, a new
group of experts in the field met in Erice,
Italy in September 2016. Their purpose
was to review the original work and to
discuss what might be needed to update and
strengthen its proposals for the new century.
They concluded that although progress
had been made in monitoring the safety
and effectiveness of medicinal products
and in the range and quality of medicines
information available, important gaps and
deficiencies still remained. To be fit for
purpose in the 21st century, the field of
pharmacovigilance would need to transform
itself to be more flexible and dynamic:
• to support clinicians in making accurate
diagnoses both of diseases and adverse
effects;
• to help patients make informed choices
about their therapeutic options, jointly
with their healthcare professionals;
• to ensure that information about medicinal
products is transparent, accurate,
accessible, relevant and timely;
• to help determine the best treatment
options and policies within mass treatment
programmes (e.g. malaria, HIV, TB) that
will have maximum public health impact
in resource-poor settings;
• to keep broader considerations in mind
such as the interactions between drugs and
the environment.
22 U PPSA LA R EPORTS / ISSU E 77
THE GROUP’S CALL FOR ACTION covered the
following topics:
• A focus on the wishes, needs, preferences
and experiences of patients in well
informed, consensual decision-making.
• T he rapid discovery of harm caused by
medicines and reporting of it through
simple, accessible means by patients or
professionals.
• T he broadening of pharmacovigilance to
healthcare vigilance.
• T he commitment of medical education to
patient-centred care and the teaching of
safety surveillance.
• T he use of modern technology and social
media to facilitate greater safety and
effectiveness in patient care.
• A broad alliance of professionals
developing methodologies and tools for
the surveillance of medicinal products to
improve how they describe benefits and
harms, and to enhance understanding and
analysis of treatments that fail or cause
harm.
• T he establishment of the highest ethical
standards in all aspects of the production
and use of medicines and the elimination
of corrupt and dangerous practices in
pharmaceuticals in some parts of the
world.
• T he making of all data and information,
including patient data and the results of
clinical trials, publically available, where
ethically possible.
• T he promotion of information and
practices that prevent harm.
• Comprehensive monitoring of all
healthcare interventions; recording and
sharing their benefits and harms to inform
and improve future patient care.
THE MEETING WAS organised by the late
Professor Giampaolo Velo from the
University of Verona, in collaboration with
UMC and the Ettore Majorana Foundation
and Centre for Scientific Culture in Erice.
The 29 participants represented a broad
range of health-related professions and came
from 13 countries.
An appreciation of the life and work of
Giampaolo Velo appears on p. 35.
Bruce Hugman
Communications Consultant, UMC
brucehugman@hotmail.com
Edwards IR, “A new Erice report  rebecca.chandler@who-umc.org
READ
considering the safety of medicines in
MOR E:
the 21st century”, Drug Safety, 2017.
Hugman B, “The Erice declaration: the
critical role of communication in drug
safety”, Drug Safety, 2006.
I NSPIR E. ENGAGE. TR A NSFOR M
The
the
There is much more to pharmacovigilance than the
collection of numbers and data. If we really want to
create a culture of drug safety, says UMC’s Rebecca
Chandler, we need to start listening to patients.
“The plural of anecdote is not data.”
T
HIS STATEMENT has been attributed
to Raymond Wolfinger, a political
scientist at the University of
California, Berkeley. It turns out
that Wolfinger’s original statement was
just the opposite: “The plural of anecdote
is data.” I was quite happy to discover the
truth, as this misquotation is often used
as an argument to support the practice of
evidence-based medicine. I was therefore
intrigued by a workshop entitled “Thinking
about patient stories: can experience become
evidence?”, held in conjunction with the
Evidence Live conference in Oxford, UK
last June. stories fit? How can we use patient stories
The workshop was attended by
approximately 30 people and led by three
I NSPIR E. ENGAGE. TR A NSFOR M
organisers: James Munro, chief executive of
Care Opinion, an independent non-profit
feedback platform for health and social care
in the UK, and André Tomlin and Douglas
Badenoch of Minervation, an Oxford-based
healthcare consultancy company. The group
consisted largely of PhD students and staff
working in the British National Health
Service.
The central theme was patient stories
as a new kind of evidence of healthcare
quality. Breakout groups had smaller
discussions exploring such questions as:
Where in the hierarchy of data do patient
to enact institutional change? How do we
best analyse patient stories, individually or
Opinion
as a group? All participants agreed that a
greater appreciation for patient stories would
improve the current practice of medicine,
as improved healthcare delivery requires
both evidence-based practice and increased
patient engagement in clinical decision
making.
PROFESSIONALS WORKING in drug safety
also need patient stories. At its very essence,
an individual case safety report is a patient
story of an adverse experience after using
a medicine. Often in pharmacovigilance
we focus on numbers and statistics. We
discuss Information Component values,
proportional reporting ratios, completeness
and vigiRank scores. Signal detection using
spontaneously reported adverse event data is
a hypothesis-generating exercise, a clinical
science which is based upon individual
reports of suspicions of causality between a
medicinal product and an adverse event.
It is logical therefore that clinical stories
contained in adverse event reports, complete
with details and context, are integral to
the development of hypotheses of drug
safety concerns. Certain details within the
patient story are integral to the building
of hypotheses of causality, such as past
medical history, concomitant medications,
time to onset of symptoms. Other details, if
provided, allow us to understand the impact
of the event upon the patient’s life, their
ability – or inability – to manage the adverse
event, and even how the patient was treated
within the healthcare system.
Pharmacovigilance is more than the
identification of causal associations between
drugs and new adverse events. It is about
creating a culture of awareness of drug
safety, and using patient stories to contribute
to an evidence base that can be used by
physicians and patients to make wise
therapeutic decisions.
Rebecca Chandler
Medical Doctor, UMC
@RebeccaChandle1
James Munro, “Treatments and
READ technologies matter, but patients
MOR E:
most want to be seen as people”,
The Guardian, 14 June 2017.
ISSU E 77 / U PPSA LA R EPORTS 23
 In focus: UK
Report Illicit
Drug Reactions
The alarming spread
of new psychoactive
sub­stances has prompted
the UK to pilot a system
for easy reporting of
harms associated with
these illicit drugs.
24 U PPSA LA R EPORTS / ISSU E 77
T
HE UK’S MEDICINES AND
Healthcare products Regulatory
Agency (MHRA) and Public
Health England (PHE) have
launched a new system to report
suspected harms associated with
New Psychoactive Substances (NPS) and
other illicit drugs. The system, called Report
Illicit Drug Reactions (RIDR), is based on
the MHRA’s Yellow Card online reporting
site and aims to provide a simple form for
healthcare professionals to report suspected
harms associated with these drugs.
NPS are designed to replicate the
effects of conventional illegal drugs such
as cannabis, ecstasy and cocaine, although
very little is known about the short- and
long-term effects they may have on the
user. Although previously known as ‘Legal
Highs’, NPS are now very much illegal in
the UK following the introduction of the
‘Psychoactive Substances Act’ last year.
Their use however still prevails and harms
associated with the products are still being
seen.
NPS have the potential to pose a serious
risk to public health. The number of new
substances identified in recent years has
grown rapidly, and hospital admissions for
poisoning by psychostimulants with abuse
potential increased by 45% over the past
five years. One in 40 young adults aged
16-25 took an NPS last year, with evidence
pointing towards widespread use among
prisoners and homeless people. Additionally,
little treatment information is available for
healthcare professionals, making managing
patients presenting with harms after taking
NPS an increasingly difficult task.
The pilot reporting system aims to
identify harms associated with NPS and
subsequently share information and
guidance with healthcare professionals.
Although RIDR is based on the Yellow Card
I NSPIR E. ENGAGE. TR A NSFOR M
Scheme, it was developed alongside
experts from PHE’s Clinical Network
on NPS to create a reporting form tailored
towards capturing NPS-related harms.
Dr Owen Bowden-Jones, consultant
psychiatrist and chair of the NPS Clinical
Network working group, said “RIDR
will allow frontline clinicians to quickly
and easily report new drug harms. The
submitted reports will help build an up-
to-date picture of the types and patterns
of emerging harms associated with New
Psychoactive Substances and other drugs.
By identifying new harms at an earlier stage,
clinicians will be better prepared to support
people presenting for help.”
S
INCE ITS LAUNCH in March, 130
reports concerning harms experienced
with 36 different substances have
already been submitted to RIDR. Many
cases included harms associated with
I NSPIR E. ENGAGE. TR A NSFOR M
In focus: UK
“RIDR will allow frontline
clinicians to quickly and easily
report new drug harms. The
submitted reports will help
build an up-to-date picture
of the types and patterns of
emerging harms associated
with New Psychoactive
Substances and other drugs.”
synthetic cannabinoids so far is encouraging. Ultimately, the hope is
Photo: Getty Images.
– substances designed to that the data collected through this project
mimic the effects of
cannabis. These include
will lead to the identification of safety signals
associated with the use of NPS and licensed
drugs such as ‘Spice’, ‘Black Mamba’ and
‘Clockwork Orange’. Many other substances
medicines, which in turn will help generate
key messages for healthcare professionals to
have been reported to RIDR, including
‘traditional’ drugs such as cocaine and
support their patients.
heroin, and some reports relate to potential
interactions between licensed medicines and
NPS.
Reports received through RIDR will
be assessed in a similar manner to those
received via the Yellow Card Scheme.
Alexander Smith
MHRA’s signalling processes will be used Pharmacovigilance Information Coordina-
to identify new harms, which will then tor, Medicines and Healthcare products
be discussed with experts from PHE and Regulatory Agency (MHRA)
the NPS Clinical Network to determine alexander.smith@mhra.gov.uk
appropriate actions. @MHRAgovuk
This is the first time that systematic data
READ https://
for harms associated with NPS are being MOR E:
collected and the number of reports received report-illicit-drug-reaction.phe.gov.uk
ISSU E 77 / U PPSA LA R EPORTS 25
 Tech update
WEB-RADR
GOES SUB-SAHARA
The WEB-RADR mobile reporting app made a well-received debut on
the African continent this year. The app fills a widely anticipated need for
a mobile reporting tool that will allow African healthcare professionals to
easily report adverse drug reactions, and to keep themselves up to date with
the latest news in medicines safety.
L
AST JUNE, a couple of months before internet through mobile devices is much
the end of the WEB-RADR project, more common than through computers, and
an African version of the mobile the use of mobile technology in the
reporting app developed for MHRA healthcare sector is increasing too. Many
in the UK, Lareb in the Netherlands and African countries and WHO had expressed
HALMED in Croatia, went live in Zambia the need for mobile reporting tools, so the
and Burkina Faso. The launch was achieved decision to create a tailored version of the
after months of intense work, which began drug safety information and reporting app
officially at the National Pharmacovigilance developed within the WEB-RADR project
Centres meeting in Oman in November 2016. was an easy one.
Smart mobile devices are widely used in The new application, unofficially called
Africa for all kinds of purposes. Access to the the White App, was born as a collaboration
between UMC, WHO, MHRA, the WEB-
RADR consortium, and the medicines
regulatory authorities in Zambia and
Burkina Faso. It is based on the apps that
WEB-RADR developed between 2015 and
2016 for the drug regulatory authorities in
the UK, the Netherlands and Croatia.
However, unlike its European counterparts
which only function in one country, the
African app can be adapted for use in
different authorities in different countries,
with language and branding to suit each
country’s needs.
THE APPLICATION WAS first released on 15
June for the Burkina Faso medicines agency
DGPML (Direction Générale de la
Pharmacie, du Médicament et des
Laboratoires). The launch was officially
announced by the Minister of Health,
Professor Nicolas Méda, who nicely
summarized the need and functionality of
the app. “Despite the rigour in their
26 U PPSA LA R EPORTS / ISSU E 77
development and production process, there
is no drug that has no adverse effects,” he
said. “The application can instantly report
adverse effects of health products to the
authorities, keep track of reported
information, and receive official news and
alerts related to the health products you are
taking or are interested in. This application
is welcome in our healthcare system.”
Dr Arsène Ouédraogo, Essential Drugs
Programme officer for WHO in Burkina
Faso, added that the WEB-RADR app
provides access to global information on
adverse events related to medicines. “In real
time, you can know what is happening in the
United States, in France, on all five
continents. The application gives all the
information in real time,” he pointed out. In
the current regulatory framework in Burkina
“With this new technology,
it is envisaged that the
rates of ADR reporting
shall improve, as anyone,
regardless of their location,
can submit an ADR report
with the click of a button.”
I NSPIR E. ENGAGE. TR A NSFOR M
?
i National
Lists:
known adverse effects
Faso, non-health workers cannot report
adverse events directly to the authority.
However, discussions on whether this should
be allowed in the future have begun.
Dr Shanthi Pal, medicines safety group
lead at WHO, attended the launch event too.
In acknowledging support from WEB-
RADR and MHRA colleagues in adapting
the app for an African setting, Dr Pal noted
that “technology needs to work for the user,
not the other way around”. The easy-to-use
app links users to national and global
databases of adverse drug reactions (ADRs),
allowing them to both report and receive
information on medicines. “This feedback
feature is essential to sustain interest in
reporting, and to share information locally
and globally,” Dr Pal remarked.
ON 29 JUNE, the Zambia Medicines
Regulatory Authority (ZAMRA) became
the second African authority to release the
app. The launch ceremony, broadcast on
national television, was opened by the
Director of Clinical Care Services -
Ministry of Health, Dr Mzaza Nthele. In his
speech, Dr Nthele encouraged everyone to
use the app to report adverse events. “It is
my belief,” he said, “that with advancing
technology such as this app, it will be easier
and quicker for health workers and indeed
our clientele to send reports of suspected
ADRs to the national centre, unlike the
paper-based forms that need to be posted
or faxed.”
I NSPIR E. ENGAGE. TR A NSFOR M
Tech update
Report to:
regulatory authority
The next step for ZAMRA will be to visit
health facilities to talk about the app and
distribute brochures to healthcare
professionals. The app will be used by
trained healthcare workers to begin with,
and it will be made available to the public
at a later stage. Mrs Bernice C Mwale,
director general of ZAMRA, expressed
high expectations for the information
campaign and the app’s release: “With
this new technology, it is envisaged
that the rates of ADR reporting shall
improve, as anyone, regardless of
their location, can submit an ADR
report with the click of a button.”
Alongside the release of the
WEB-RADR app in Africa, an
advertising campaign was
launched with the key message
‘Hold health in your hands’.
The promotional material was
produced both in English for
the Zambian audience and in
French for the Burkina Faso
users. The images in this article
give a flavour of the campaign.
Magnus Wallberg
Technology Evangelist, UMC
magnus.wallberg@who-umc.org
@CMWallberg
Afifa Trad, “Health information tech-
READ nologies in resource-poor settings”,
MOR E:
Uppsala Reports 76.
ISSU E 77 / U PPSA LA R EPORTS 27
 Tech update In focus: Japan

Unveiling the White App Centralised checkpoints to improve

The WEB-RADR reporting app recently launched in Africa integrates several
UMC resources and tools. Here’s how it works.
hospital reporting in Japan
By exploiting the national hospital network and rerouting The initiative has been running for
almost two years now and preliminary data
1. Download and install ADR reports through designated hospital safety hubs, Japan from Hokkaido University Hospital show
that, at least in some parts of the country,
The app is downloaded from Google Play or App Store. Following installation,
the user is prompted to select an authority to report to (this can be changed is hoping to collect better reports from healthcare professionals. the system is working well. The authors
hope that, by making use of the Japanese
later, if needed). By creating a personal account, the user can view sent reports,

E
and some information will be auto-filled upon reporting. VERY YEAR, the Pharmaceuticals
and Medical Devices Agency
(PMDA) in Japan receives
2. Add drugs to watch list approximately 50,000 reports of
WHODrug names are delivered to the app via a web service and filtered to adverse drug reactions (ADRs). Only one
display only medicines and substances relevant to the chosen country. Medicines tenth of these are submitted by healthcare
of interest can be added from the country-specific list to a watch list, where the professionals, while the remaining 90% are
app will show news and reporting statistics. provided by drug manufacturers. The
conventional reporting pathway begins with
the observation of a suspected adverse event
at the hospital. The observation is passed on
3. Retrieve statistics to the pharmacovigilance staff at the drug’s
Statistical data on adverse events observed for a substance are retrieved in real manufacturing company, which in turn
time from VigiBase via the VigiAccess API. This is the same as the service used reports it to PMDA.
in the publicly available VigiAccess tool. Data can be stratified by reaction, year Unfortunately, the quality of manu­facturer
of reporting, patient gender, patient age or continent. reports is often sub-optimal and the reasons
for this are many. Manufacturers are
sometimes unable to retrieve sufficient
4. Report side effect clinical information on the case from
physicians, and reporters tend to lack the
Adverse event reporting can be done from the watch list by entering adverse
appropriate skills to write a good medical
events and medicine names, as free text or via MedDRA and WHODrug.
report that will support causal relationship
Medicine names can be selected via the same country-specific WHODrug list.
between drug use and adverse event.
Users can save unsent reports for later viewing, or revisit ones previously sent by
Healthcare professionals’ reports, on the
logging in to their account. Once a report has been completed, it is sent via the
other hand, often help identify the most
app to the national pharmacovigilance authority. The White App is connected
serious adverse reactions to medicines.
to VigiFlow, so the report ends up directly in the authority’s list of reports. The
Around half of all severe adverse events
app can also be connected to another pharmacovigilance system, as long as that
evaluated at PMDA in 2015 came directly
system implements the standardised WEB-RADR API. After being assessed
from healthcare professionals, underscoring
by the authority, a copy of the report is automatically sent to VigiBase via the
the essential role they play in ADR reporting
VigiBase API.
and the importance of getting them to
report more frequently.
hospital network and rerouting ADR reports
According to the revised Pharmaceutical through hubs that connect smaller hospitals
Affairs Act of November 2013, Japanese to PMDA, reporting quality around the
healthcare professionals are required to send country will increase without the need for
ADR reports to PMDA, the regulatory additional IT infrastructure.
authority that, in collaboration with the
Ministry of Health, Labour and Welfare,
implements pharmacovigilance and drug
safety measures in Japan. Healthcare
professionals are obliged to report ADRs in
a designated format provided by PMDA,
and reports must include a clinical narrative.
IN EARLY 2016, some hospitals in Japan
launched an initiative to improve the quality
of healthcare professional-derived reports. A
medical advisory section was set up in
selected regional hospitals, with the aim of
helping other, often smaller, hospitals in the MANUFACTURERS
area when a suspected adverse event occurs.
Each section receives drafts of ADR reports
from private, community and university- REGULATORY AUTHORITY
affiliated hospitals in the region, edits them
and sends them to PMDA.
To reinforce hospital safety, selected
Meguru Watanabe
hospitals also received a budget increase to
Senior Reviewer, Office of Safety II,
establish an ad hoc department, whose staff
Pharmaceuticals and Medical Devices
consists of physicians, pharmacists and
Agency (PMDA)
registered nurses responsible for general
watanabe-meguru@pmda.go.jp
safety issues. They are responsible for
writing ADR reports for PMDA and
collaborating with pharmaceutical READ www.pmda.go.jp/english
MOR E:
companies on ADR reporting.

5. Check news feed

Each authority can provide an RSS feed with news about drug safety in their
country. Individual news items can be tagged with substance names, so that the
news feed can be tailored to the user’s watch list preferences.

Photo: Shutterstock.
Magnus Wallberg
READ Magnus Wallberg, “Drug-name look-up in mobile apps made easier”, Uppsala Reports 76.
Technology Evangelist, UMC
MOR E: Magnus Wallberg, “Real-time pharmacovigilance with the VigiBase API”, Uppsala Reports 75.
magnus.wallberg@who-umc.org
@CMWallberg

28 U PPSA LA R EPORTS / ISSU E 77 I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 29
 In focus: Kuwait
A social media project
to raise drug safety
awareness in Kuwait
Although there is yet to be a national pharmaco-
vigilance centre in Kuwait, Reem Al-Essa launched
a social media campaign to inform the public in her
country about adverse effects and how to report them.
P
HARMACOVIGILANCE HAS BEEN a
growing challenge in Kuwait and
the rest of the Gulf Cooperation
Council (GCC) countries. Ensuring
patient safety has been the target of all
regulatory authorities since their inception
in the region in the mid 20th century. The
implementation of the Common Technical
Documents harmonized the approval
process for pharmaceutical and
biotechnology products in the Gulf states
over the last five years. This improvement
of pre-market assessment drew regulatory
attention towards the need to monitor the
safety and effectiveness of medicines after
marketing approval.
Oman was the first country in the GCC
region to set up an adverse drug reaction
(ADR) monitoring centre, and has been a
full member of the WHO Programme for
International Drug Monitoring since 1995.
Saudi Arabia followed in 2009 and the
United Arab Emirates in 2013, while
Bahrain and Qatar are associate members.
KUWAIT WAS ONE of the first Arab states to
recognize the need for a pharmacovigilance
centre to monitor the safety of locally-
approved medicines. A study published in
30 U PPSA LA R EPORTS / ISSU E 77
1985 evaluated spontaneous ADR reporting
patterns between 1981 and 1984, and
advocated the establishment of a national
ADR monitoring centre. The study showed
that of 704 reports received from 26
hospitals and health clinics, 90.5% were
classified as possible drug-ADR causal
relationships. Based on these results, the
health authority in Kuwait expressed its
intention to establish a national ADR
monitoring centre.
The regulatory authority has been
vigilant to any action taken by recognized
regulatory systems and it has taken
immediate action regarding the safety of
registered products accordingly.
Unfortunately, the local health authorities
have not yet established a legal framework
for pharmacovigilance, although all
elements for a well-developed system exist:
an established unit, experienced
professionals, guidelines and technological
tools; all under the regulatory directorate at
the Ministry of Health.
For a pharmacovigilance system to see
the light of day in Kuwait, public awareness
of medicines safety needed to be raised, and
that is where the idea for Report Me Kuwait
originated. The aim of the project is to teach
I NSPIR E. ENGAGE. TR A NSFOR M
patients, consumers and caregivers why they
should report adverse effects, and how,
when and where to submit a report. The
project also aims to raise healthcare
professionals’ awareness of the urgency to
report adverse effects encountered in their
clinical or community practice.
SOCIAL MEDIA WAS SELECTED to allow for
direct interaction with the target audience.
The spread of information has never been so
fast until social media and mobile
technology were invented and made such a
tremendous social, cultural, educational and
political impact. In Kuwait and other Arab
countries, people spend most of their online
time on mobile devices. The majority of the
population, between 20 and 65 years of age,
uses social media to share information, build
a social image, demonstrate new ideas,
interact and nurture relationships, or
participate in new interventions to make
positive changes to our world. The power of
social media offered an opportunity for
Report Me Kuwait to spread its word past
national boundaries to all other Arab
countries, simply using the mobile devices
everyone holds in their hands.
Report Me Kuwait is present on all the
A Kuwait shopping mall (Reem Al-Essa).
I NSPIR E. ENGAGE. TR A NSFOR M
In focus: Kuwait
major social media platforms and currently
has over 2,600 followers on LinkedIn, about
1,300 on Instagram, and a growing presence
on Facebook, Twitter, Snapchat and
YouTube. Posts include short videos,
informative cards and brochures about
medicines safety, the need to report adverse
events, and the impact of pharmacovigilance
on society. The project has been featured in
local TV shows and newspapers, and the
first signs of its impact on the public are
becoming visible.
SINCE ITS INCEPTION in January 2017, eight
ADR reports have been forwarded to the
local health authority via Report Me Kuwait,
a good number considering the absence of
an official pharmacovigilance framework in
the country and the general lack of
awareness on the topic. The eight reports
came from consumers, who were very keen
to report the adverse events but did not
know where or how to report until Report
Me Kuwait offered a solution.
Users wishing to report an adverse event
can reach out to Report Me Kuwait and will
receive a link to an electronic reporting form
that can be forwarded directly to the health
authority. The form also contains contact
information for the prescribing healthcare
professional or the pharmacist who
dispensed the drug, so that the health
authority can communicate with them,
should they find the ADR report to be
critical.
Report Me Kuwait followers increase
daily, a sign that there is a growing interest
in pharmacovigilance, and it is hoped that
the project will serve as inspiration for
similar initiatives in the Arab world in the
future.
Reem K. Al-Essa
Senior Pharmacy Specialist, Drug
Inspection Administration, Drug
and Food Control Sector, Ministry of
Health, Kuwait
report.me.kwt@gmail.com
@Report_Me_Kwt
ISSU E 77 / U PPSA LA R EPORTS 31
 In brief In brief

Join the
Annie & Mac went to India! conversation on
social media!

Romina Heredia (here with Elki Sollenbring, left) visited UMC in October to learn about
the new VigiFlow. Ms Heredia manages the ADR database for Argentina’s national
pharmacovigilance centre ANMAT, and while at UMC, she also held a presentation on the
status of pharmacovigilance in Argentina.

Around 60 children in Ghaziabad received our pharmacovigilance comic book Annie & Mac’s Adventures to learn about fake medicines and side effects.
Photo: Pharmacovigilance Programme of India.

Jaber Jaber from the Jordan Food and Drug

Administration (JFDA) visited UMC in October.
The Pharmacovigilance Programme of India (PvPI) has been appointed as WHO Collaborating Centre Dr Jaber is vice head of the Rational Drug Use and
for Pharmacovigilance in Public Health Programmes and Regulatory Services. At the official launch Pharmacovigilance section at JFDA. During his
ceremony in October 2017, Dr RK Vats from the Ministry of Health & Family Welfare unveiled the visit, he discussed the future of pharmacovigilance
foundation stone in the presence of representatives from WHO headquarters. Photo: PvPI. in Jordan with our colleagues at Global Services.
At the Uppsala Health Summit in October, UMC’s Rebecca Chandler and Paula Alvarado
led a workshop on safety monitoring of new drugs and vaccines in emergency situations.
Participants drew a list of suggestions to integrate pharmacovigilance practices in the
response to infectious disease threats.

32 U PPSA LA R EPORTS / ISSU E 77 I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 33
 Research
PML and Alemtuzumab.print.pdf 1 2017-10-09 13:17

1. 2.
Tailoring signal detection methodologies in
a global database to focus on safety concerns

IN MEMORIAM
reported by patients
Watson S 1, Chandler RE 1, Taavola H 1, Härmark L 2, Grundmark B 1,3, Zekarias A 1, Star K 1,4, van Hunsel F2.
1 Uppsala Monitoring Centre, Uppsala, Sweden. 2 Netherlands Pharmacovigilance Centre Lareb, 's-Hertogenbosch, The Netherlands. 3 Department of Surgery, Uppsala University, Uppsala, Sweden.
4 Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. I never suspected
[the drug] to have
any role in my anxiety or
Background
… Horrendous
headaches, feeling panic attacks until
my skull was going I stopped..
A recent systematic review summarised the current evidence on the value of patient reporting to explode!
into pharmacovigilance systems. [1] However, descriptions of methodologies for using patient
reports in signal detection are scarce, and published experiences of how patient reports are
used in national pharmacovigilance centres are limited to a few countries. [2-3] Severe itching,
soreness and
inability to sit.

Objectives
rt
To explore the contribution of patient reports to signal detection in the WHO global po
re
R
database of individual case safety reports (ICSRs), VigiBase. AD

Methods
Data was retrieved from VigiBase in September 2016. Suspected
duplicate reports and reports from studies were excluded. Drug-ADR
combinations were generated and restricted to report series with:

M
• At least 50% patient ICSRs
Y

• at least one patient report received after 2014

CM

MY
RESTRICTED
CY

SIGNAL
CMY

• ≥ 2 countries
K

• ≤ 30 patient ICSRs

vigiRank4, an algorithm using multiple-strength-of-evidence aspects, Analyses of reports in the WHO global database of individual case safety reports, VigiBase • February 2017

was used to prioritize combinations for assessment. In the assessment

of each combination, the product information for health care providers
as well as patient information leaflets were reviewed for information
on ADRs.

Focus on patient reports

Results Signals in this issue

• Amitriptyline – Dry eyes

A total of 212 drug – ADR combinations were assessed which
• Desloratadine – Depression
resulted in 8 signals communicated within the WHO programme • Desogestrel – Severe psychiatric
for international drug monitoring. Reviews of patient information disorders: panic attack, suicidal
ideation and self injurious behaviour
leaflets were performed; examples of poor consistency with • Levothyroxine – Panic attack
product information for physicians were found. Patient • Noscapine – Abdominal pain, chest
pain and headache
narratives were confirmed to provide details regarding
• Pregabalin – Visual colour distortions
the experience of the ADR and its impact on the
• SGLT-2 inhibitors – Genital pruritus
quality of life of the patient; furthermore, there
• Systemic hormonal contraceptives –
is evidence in narratives that patients make Loss of libido
Please direct all correspondence regarding signals presented in

causality and benefit/harm assessments

this document to Uppsala Monitoring Centre

themselves.

Conclusions
Safety concerns described in patient
reports can be identified in a global
database including previously unknown
ADRs as well as new aspects of known ADRs.
Professor Giampaolo Velo
Patient reports provide unique information
valuable in signal assessment, and they should
be included in signal detection as far as (1943-2017)
is possible.

3.
WHO Pharmaceuticals Newsletter References
1. Inácio P, Cavaco A, Airaksinen M. The value of patient reporting to the pharmacovigilance system: a systematic review.
Br J Clin Pharmacol 2017; 83: 227-246.
The signals from UMC are available to the public 2. van Hunsel F, Talsma A, van Puijenbroek E, de Jong-van den Berg L, van Grootheest K. The proportion of patient reports of suspected ADRs to signal
detection in the Netherlands: case-control study. Pharmacoepidemiol Drug Saf. 2011 Mar;20(3):286-91.
through the WHO Pharmaceuticals Newsletter with
WE ARE SAD TO REPORT the death last meetings and was member of the UMC published online in Drug Safety on the
3. Hazell L, Cornelius V, Hannaford P, Shakir S, Avery AJ; Yellow Card Study Collaboration. How do patients contribute to signal detection? : A
retrospective analysis of spontaneous reporting of adverse drug reactions in the UK's Yellow Card Scheme. Drug Saf. 2013 Mar;36(3):199-206.
the aim to disseminate information on the safety and 4. Caster O, Juhlin K, Watson S and Norén GN. Improved Statistical Signal Detection in Pharmacovigilance by Combining
Multiple Strength-of-Evidence Aspects in vigiRank Drug Saf (2014) 37 (8) 617-628

Signal Review Panel. same day of his death.

efficacy of pharmaceutical products.
https://goo.gl/64bgV4
Disclosure
The authors are indebted to all the patients who reported their experiences as well as the national centres contributing the reports to VigiBase. The
opinions and conclusions in this study are not necessarily those of the various national centres, nor of WHO. We would also like to thank Jeltje Boer,
August of Professor Giampaolo Velo.
After graduating with honours in Medi- Giampaolo was deeply involved in many
Ellen Ederveen and Niklas Norén for their contributions in the workshop.

Uppsala Monitoring Centre (UMC)

Box 1051, SE-751 40 Uppsala, Sweden
cine at the University of Bologna, and a GIAMPAOLO AND HIS GROUP were actively scientific societies. He was co-founder,
period in the UK working with John Vane involved in many projects and had scientific chairman and then honorary president of
+46 18 65 60 60 www.who-umc.org

on prostaglandins and inflammation, collaborations with important groups the European Association for Clinical
4. Giampaolo went back to Italy as full working in pharmacovigilance and phamaco- Pharmacology and Therapeutics (EACPT),
The future of evidence in a post-truth age of alternative facts Print.pdf 1 2017-09-04 11:04

1. Presented at the 17th Annual

ISoP Meeting in October 2017. professor of Pharmacology at the Univer- epidemiology, worldwide. He was also the and president of the International Society
sity of Verona. There, he was director of founder and director of the International of Pharmacovigilance (ISoP) from 2003 to
2. Awarded first prize at the the Institute of Pharmacology and director School of Pharmacology at the Ettore 2006. From 1994, he was founder and
17th Annual ISoP Meeting in of the Clinical Pharmacology Unit at the Majorana Foundation and Centre for editor-in-chief of the bulletin FOCUS
October 2017. University Hospital. Scientific Culture in Erice, Sicily. Farmacovigilanza. In his last years and
Giampaolo and his group started work Erice was typical of the man: a wonderful even after retirement in 2012, he was
3. Presented at the 33rd in pharmacovigilance and pharmaco- place in a pre-medieval town, a high actively working in the new field of eco-
International Conference on scientific level of discussion, but very high pharmacovigilance, the adverse effects of
epidemiology in the 1980s. They rapidly
Pharmacoepidemiology &
became one of the most important such collegiality and an informal, even goliardic, drugs in the environment, the term first
Therapeutic Risk Management
C

groups in Italy. The Institute of Pharma- atmosphere. Reports from many of the coined by him in 2007.
in August 2017.
M

CM

MY

CY

CMY

cology was the first Regional Centre of
4. Presented at the 77th FIP World Pharmacovigilance in Italy and from
Congress of Pharmacy and 1995 a Reference Centre for Education
Pharmaceutical Sciences in and Communication within the WHO
September 2017. Programme for International Drug
Monitoring. In the 1990s, the Verona
group represented Italy in the WHO
View our posters here:
www.who-umc.org/ Programme, sending reports to VigiBase
archive/umc-posters from Veneto and other Italian regions.
Giampaolo attended many WHO annual
Erice workshops have been published. The
most important ones were probably the
Erice Declaration on communicating drug
safety information in September 1997 and
the Erice Manifesto in July 2006. These
documents were discussed and updated
during a new meeting in Erice in September
2016, the last to be organized by Giampaolo,
who was then already ill but nevertheless
active. The report of this meeting was
A man of great passion and curiosity
for everything related to clinical pharma-
cology, a tireless worker and traveller, he
was also known for his kindness, informa-
lity and great sense of humour. He knew
almost everyone in our field and was a
friend to many.
We will remember him fondly forever.
Ugo Moretti, Roberto Leone and Anita Conforti

34 U PPSA LA R EPORTS / ISSU E 77 I NSPIR E. ENGAGE. TR A NSFOR M I NSPIR E. ENGAGE. TR A NSFOR M ISSU E 77 / U PPSA LA R EPORTS 35
 Uppsala Reports ISSN 1651-9779
Pharmacovigilance Meetings
2017 – 2018
4-5 December 2017 29 January-9 February 2018 21-24 April 2018
Intelligent Automation in 4th Asia Pacific Pharmacovigilance ISPE 2018 Mid-Year Meeting
Pharmacovigilance Training Course Toronto, Canada
Boston, USA Mysore, India International Society for Pharmacoepidemiology
International Society of Pharmacovigilance (ISoP) JSS University & Uppsala Monitoring Centre (ISPE)
www.isoponline.org (UMC) www.pharmacoepi.org
www.jssuni.edu.in; www.who-umc.org @ICPE
@ISoPonline
@UMCGlobalSafety
2-4 May 2018
4-6 December 2017 21-22 February 2018 Medical Aspects of Adverse Drug
Pharmacovigilance
London, UK
Back to Basics in Pharmacovigilance Reactions
Fareham, UK Fareham, UK
Management Forum Ltd
Drug Safety Research Unit (DSRU) Drug Safety Research Unit (DSRU)
www.management-forum.co.uk
www.dsru.org www.dsru.org
@DSRUDrugSafety @DSRUDrugSafety
3-5 January 2018
Euro-Asian Pharmacoepidemiology 7-9 March 2018 21 May-1 June 2018
Congress 2018 (EAPEC 2018) Advanced Pharmacovigilance 20th International Pharmacovigilance
Shiraz, Iran London, UK Training Course
EAPEC Management Forum Ltd Uppsala, Sweden
www.eapec2018.ir www.management-forum.co.uk Uppsala Monitoring Centre (UMC)
www.who-umc.org
11-12 January 2018 15-16 March 2018 @UMCGlobalSafety
5th ISoP-UMC Training, in ISoP Mid Year Training Course
collaboration with the ISoP Canberra, Australia
China chapter International Society of Pharmacovigilance (ISoP)
Shenyang, China www.isoponline.org
International Society of Pharmacovigilance (ISoP) @ISoPonline
& Uppsala Monitoring Centre (UMC)
www.isoponline.org; www.who-umc.org
@ISoPonline @UMCGlobalSafety

22-24 January 2018 Psst! Follow us on social

media for news and updates.
Pharmacovigilance and Risk
Management Strategies Conference
Washington, DC, USA
DIA
www.diaglobal.org www.linkedin.com/company/ www.twitter.com/
@DrugInfoAssn Uppsala-Monitoring-Centre UMCGlobalSafety

24 January 2018
11th Pharmacovigilance Conference www.facebook.com/ www.youtube.com/c/
London, UK UppsalaMonitoringCentre UppsalaMonitoringCentre
Medicines for Europe
www.medicinesforeurope.com
@medicinesforEU

Uppsala Monitoring Centre (UMC) is an independent non-profit foundation and centre for international service and scientific
research. Our vision is a world where all patients and health professionals make wise therapeutic decisions in their use of
medicines. Our mission is to support and promote patient safety through effective global pharmacovigilance practise.

36 U PPSA LA R EPORTS / ISSU E 72

77 I NSPIR E. ENGAGE. TR A NSFOR M