1. Panorama of actions patient organisations
can take in pharmacovigilance
EURODIS conference - capacity building for expert patients and researchers
Mitul Jadeja June 2018
2. Mitul Jadeja - EURODIS PV training
This presentation
How to familiarise
yourself with the
reporting methods of
NCAs and
regulatory outputs
How to explain PV
to patients and
engage
Planning a
campaign
Measuring success
Examples of some
initiatives and
campaigns
encourage patient
reporting
Practical tools you
can use
Mitul Jadeja - EURODIS PV training
3. Mitul Jadeja - EURODIS PV training
Why do we need pharmacovigilance?
Clinical trials Real world setting
“the science and activities
relating to the detection,
assessment,
understanding and
prevention of adverse
effects or any other drug-
related problem”
4. 0
20
40
60
80
100
120
1 10 100 1000 10000
Frequency of ADR
TimetoonsetofADR
Mapping safety & need for PhV
Known at licensing
• Pre-marketing data have important limitations
• Pre-clinical data: low predictive value
Clinical trial data provide
provisional evidence of
safety but:
- too small
- limited duration
- limited populations
- not representative of
real world
6. Mitul Jadeja - EURODIS PV training
Anything to do with
a medicine I’ve
been given that
causes me harm
‘Suspected’ ADR or
‘side effect’
report to the
national ADR
reporting system
What’s in a definition?
• Adverse reaction; adverse drug reaction (ADR), Adverse effect, Undesirable effect: A response to a medicinal product
which is noxious and unintended [DIR 2001/83/EC Art 1(11)]. Response in this context means that a causal relationship
between a medicinal product and an adverse event is at least a reasonable possibility. Adverse reactions may arise from
use of the product within or outside the terms of the marketing authorisation or from occupational exposure [DIR
2001/83/EC Art 101(1)]. Conditions of use outside the marketing authorisation include off-label use, overdose, misuse,
abuse and medication errors.
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/05/WC500143294.pdf&rct=j&frm=1&q=&esr
c=s&sa=U&ved=0CBoQFjABahUKEwjolcC8yLzIAhUClA0KHXLNDOU&usg=AFQjCNHt2ArigMn1WpHp2KejiS76RDNYxA
• GVP Module VI.B.6.3 -medication error: ‘any unintended error in the prescribing, dispensing or administration of a
medicinal product while in the control of the healthcare professional, patient or consumer’ - this definition is focused on the
management and reporting of adverse reactions to medicinal products and does not cover all stages of the medication use
process where an error may occur and where there is an adverse reaction, e.g. preparation for administration.
http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000570.jsp
7. Mitul Jadeja - EURODIS PV training
Do you know your national
medicines regulators?
• EMA has a list of NCAs:
http://www.ema.europa.eu/em
a/index.jsp?curl=pages/medici
nes/general/general_content_
000155.jsp
• National PV centres
• RMCs
8. Mitul Jadeja - EURODIS PV training
www.adrreports.eu
• Accessible in multiple
languages
• List of national
medicines regulatory
authorities in the EEA
• Information on
reporting
• Access reports
submitted to
Eudravigilance
• Like iDAPs
• Online
• App
• clinical systems
• Paper
• phone Mitul Jadeja - EURODIS PV training
10. Mitul Jadeja - EURODIS PV training
Black Triangle Scheme ▼
• Risk benefit profile knowledge limited - Report all ADRs
• Materials: video and printable leaflets in many languages
http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/genera
l_content_000586.jsp&mid=WC0b01ac05807257a3
When does a medicine have a ▼?
• new active substance;
• biological medicine, such as a vaccine or a medicine derived
from plasma (blood);
• given a conditional approval (where the company that
markets the medicine must provide more data about it) or
approved under exceptional circumstances (where there are
specific reasons why the company cannot provide a
comprehensive set of data);
• the company is required to carry out additional studies: for
instance, to provide more data on long-term use of the
medicine, or on a rare side effect seen during clinical trials.
• Other medicines can also be placed under additional
monitoring, based on a decision by the Agency's
Pharmacovigilance Risk Assessment Committee (PRAC).
11. Mitul Jadeja - EURODIS PV training
Cystadrops (mercaptamine)
• for treatment of cystinosis
• typically diagnosed prior
to age 2.
• genetic metabolic disease
that causes an amino
acid, cystine, to
accumulate in various
organs of the body.
Cystine crystals
accumulate in the
kidneys, eyes, liver,
muscles, pancreas, brain,
and white blood cells.
• MA issued, +ve COMP
opinion, Jan 17
12. Mitul Jadeja - EURODIS PV training
iDAP: interactive drug analysis profile
13. Mitul Jadeja - EURODIS PV training
Information on orphan designations
14. Mitul Jadeja - EURODIS PV training
Accessing outputs of regulatory action
• Patient Safety warnings
• Product information (MA):
SmPCs & PILs, and labelling
• EU Public Assessment Reports
• Safety Communications e.g. Medicine
Alerts and DHCPs
• Rare disease designations
• Pubic hearings
• Committee information
• Additional Monitoring lists
• Risk Management Plans
• Educational material – HPRA
• Newsletters – e.g. Drug Safety Update
• Sign up to updates and RSS feeds
http://www.ema.europa.eu/ema/index.jsp?curl=p
ages/home/Home_Page.jsp&mid=
18. Mitul Jadeja - EURODIS PV training
Pharmacovigilance legislation
- ‘take all appropriate measures’
“Directive 2010/84/EU… Article 102. The
Member States shall:
….take all appropriate measures to encourage
patients, doctors, pharmacists and other
health-care professionals to report suspected
adverse reactions to the national competent
authority [MHRA]; for these tasks, consumer
organisations, patients organisations and
healthcare professionals organisations may be
involved as appropriate.”
Preaching to the converted? Need to raise general awareness
19. Mitul Jadeja - EURODIS PV training
Responding to change: drivers
for initiatives & campaigns
– Protecting public health and patients
– ADR statistics
– Underreporting & impact of ADRs
– pharmacovigilance legislation implications:
• Definition of ADR
• EU wide patient reporting
• Additional Monitoring - ▼
• Support for strengthening ADR reporting;
product information messages
– HMA support: same 4 pillars
– Independent review e.g. HTA, Avery report
recommendations
– Maintaining/strengthening ‘regularory position’
– SCOPE and ICMRA
Directive 2010/84/EU and Regulation 1235/2010
20. Mitul Jadeja - EURODIS PV training
Patient Information Leaflet
For medicinal products subject to additional monitoring ONLY:
The black symbol and the statements should only appear immediately after the declaration of the
name of the medicine. The black symbol shall be a black inverted equilateral triangle: the symbol
shall be proportional to the font size of the subsequent standardised text and in any case each
side of the triangle shall have a minimum length of 5 mm. For the purpose of preparing the
product information annexes please use the Black Triangle as presented in the template.
‘▼ This medicine is subject to additional monitoring. This will allow quick identification
of new safety information. You can help by reporting any side effects you may get. See
the end of section 4 for how to report side effects.’
For ALL medicinal products:
The following sub-heading should appear at the end of section 4
‘Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card
Scheme at: www.mhra.gov.uk/yellowcard By reporting side effects you can help provide more
information on the safety of this medicine.’
21. Mitul Jadeja - EURODIS PV training
Patient reporting in EV – a measure of patient
engagement? Workshop on measuring the
impact of PV activities
• Patients are more
likely to report ADRs
for substances for
genitourinary system
and systemic
hormonal preparations
than HCPs – aligned
with the results for
Indications (2009-15)
• 13/20 most frequently
reported terms are
identical as HCPs.
• Marin Banovac
6/12/16
22. KISSS – keep it simple, short and specific
• Experienced a side effect? Please report!
• Always read the PIL (lists known side effects)
• Speak to a healthcare professional for advice
– Explain the benefit & to public health
– Don’t delay, report today ‐ don’t wait for someone else to
report it
– Only a suspicion is needed, even if you
• don’t see a connection between the drug & ADR
• think the ADR doesn’t last for long, isn’t severe, or you think it‘s from
long term use
• Don’t worry about ▼, off‐label use, med errors….. Avoid scare tactics Mitul Jadeja – EURODIS PV training
22
23. Mitul Jadeja - EURODIS PV training
Developing clear messages based on
research
Patients
• Your report is important to help make medicines
safer
• Only a suspicion is needed to report
• How to report
• Always read the Patient Information Leaflet
supplied with your medicine for more
information on side effects
• Speak to your HCP for further advice
Parents
• Reports from parents like you are very useful.
• Parents know their child better than anyone and
can tell us about things that healthcare
professionals can’t.
• We want parents to send reports even if they
only have slight concerns about a medicine –
you don’t need to be certain that a medicine has
actually caused a side effect to send a report.
• Reports are confidential. We won’t share the
information on your report with your child’s
doctor if you don’t want us to.
Consider integrating the following set of key messages for developing basic patient messages for promotion purposes
(from campaign material used):
24. Mitul Jadeja - EURODIS PV training
Proactive pyramid of engagement
opportunities
• Offer a menu to NCA’s
• Empowerment vs Engagement
• Consider:
‐ Budget
‐ Resource
‐ Time to engage
‐ Training
‐ Local vs national
‐ Helplines
‐ RMCs
‐ Registries
‐ MoUs
‐ Tenders
Decision
making
Consulting
Committee
&
Management
Research &
Project
work
Social
media
Forming
formalised
partnership
&
agreement Campaign
work –
ADRs can
be the first
catalyst
Educational
programmes
Educational
materials
28. Mitul Jadeja - EURODIS PV training
Where do you begin?
Where are
you now?
Where do
you want to
be?
How are you
going to get
there?
(in relation to ADRs!)
29. Mitul Jadeja - EURODIS PV training
Where are you now?
• ADR statistics
– helps focus efforts
– example tables in guidance
• Stakeholder analysis
– helps shape strategy & messages
– basic stakeholder analysis
matrix in guidance
– Understand your audience
• Benchmarking
– focuses efforts, helps measure, an
engagement opportunity
– examples of through polls and surveys
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
9,000
patients pharmacists nurses doctors
‘Combined qualifications’ from
‘direct’ Yellow Cards reporting
2011 2012 2013 2014 2015 2016
30. Benchmarking questions
ADR reporting
Who would you report an unexpected
side effect with a medicine to? (Or
ADR if aimed at HCPs)
If a patient reports an ADR to you, to
whom or to which organisation would
you report it, if anyone?
Which, if any, of the following things
would help you to report ADRs?
Medicines Regulation
Who do you think regulates medicines to make sure they
work and are safe enough to use?
How much, if anything, would you say you know about
the way medicines are regulated?
31. Mitul Jadeja - EURODIS PV training
Where do you want to be?
• Across the national health service, where will you choose to raise
awareness levels? Why?FocusFocus
• What about patients? Their organisations?StakeholdersStakeholders
• How is your work related with other organisations or regulators?InteractionsInteractions
• What collaborations and partnerships can be formed?PartnershipsPartnerships
• What do you need to implement your strategy?ImplementationImplementation
• What does it look like? Can you compare before and after?Measuring successMeasuring success
• What can you do once for a lasting impact on ADR reporting and
your audiences?Sustainable effortsSustainable efforts
32. Mitul Jadeja - EURODIS PV training
What to measure?
Real impact is the number of suspected ADR reports
(consider measuring per population)
• Outputs – e.g. numbers of posters, books, leaflets, posters, partnerships etc.
• Key messages and out-takes – e.g. where to report, understanding of the
concept of reporting, understanding the value of reporting, the effect of reporting,
etc.
• Outcomes – changes in suspected ADR reporting numbers, changes in
behaviours, attitudes, opinions which can be measured.
• Examples from: GR, SE, ES, IS, MT, NL, FR, HR, DK, UK
33. Mitul Jadeja - EURODIS PV training
Working with stakeholders
• Improves the ability to reach target
audience
• Deliver messages effectively and reduces
message fatigue
• Provided potential additional opportunities
• Feedback on approach and effectiveness
• Cost effective
– Regional PV centres
– Academic organisations
– Professional bodies
– Hospitals
– Charities/voluntary organisations
– Government agencies
34. ADR
reports
ADR
reports
monitor numbers
before and after,
consider per x
population
monitor numbers
before and after,
consider per x
population
dashboards,
management
reports
dashboards,
management
reports
SignalsSignals
monitor numbers
before and after
monitor numbers
before and after
signal
dashboards,
PRAC signals,
regulatory action
signal
dashboards,
PRAC signals,
regulatory action
Attitudes
and
behaviour
Attitudes
and
behaviour
analyse changes
before and after
analyse changes
before and after
surveys, pols,
interviews,
workshops, focus
groups, action
plans
surveys, pols,
interviews,
workshops, focus
groups, action
plans
Social
media
Social
media
views, retweets,
likes, shares,
polls, follows,
followers, blogs,
RSS subscribers
views, retweets,
likes, shares,
polls, follows,
followers, blogs,
RSS subscribers
management
reports, simple
counts and
software tools
management
reports, simple
counts and
software tools
WebsiteWebsite
web analytics to
monitor trends
over time, site
search terms,
downloads,
views
web analytics to
monitor trends
over time, site
search terms,
downloads,
views
analytical
software such as
Google analytics,
Webtrends
analytical
software such as
Google analytics,
Webtrends
Measuring success: 1) Key areas 2) what
to measure 3) how to measure
1
2
3
38. Mitul Jadeja - EURODIS PV training
Challenges
• Time taken to engage with stakeholders & continuing engagement
• Multiple changes in staff
• Negotiation and influencing – low/no cost
• Measuring success - ‘some’ communications can be difficult to show
any immediate cultural changes
• Opinions and consensus - political
• Press work & Patient case studies
• Flexibility in approaches to working
40. Mitul Jadeja - EURODIS PV training
SCOPE guidance
• Raising and Measuring Awareness
Levels for ADR Reporting Systems
through Campaigns and Regional
Monitoring Centres
• Contains huge annex of case
studies by country containing
materials
• e.g. ANSM call for
patients/organisations to report and
get involved in studies
Author: Mitul Jadeja
41. Mitul Jadeja - EURODIS PV training
SCOPE animation https://www.youtube.com/watch?v=3et5LdYLc8M
42. Mitul Jadeja - EURODIS PV training
Suspected side effect?
43. Mitul Jadeja - EURODIS PV training
• In UK, over 6K.
• Pilot findings
• Similar levels of reports of serious reactions
• Fewer reactions to black triangle drugs
• Less complete reports: but no difference in causality, or proportion of
unlabelled reactions
• More information on impact of ADRs on quality of life
• Low levels of consumer awareness of the YC Scheme
Reporting helps
44. Mitul Jadeja - EURODIS PV training
Essential Information
1. Suspect drug
2. Description of the side effect
3. Patient details
(e.g. age, sex, weight)
4. Reporter details
Additional Information
• Relevant past medical history
• Test results
• Whether reaction was serious
• Name and address of reporter
• * GP details
(patient’s consent required)
Important Information
• Dose and indication of the suspect
drug and dates of the treatment
• Dates the suspect reaction started
and stopped
• Outcome of the reaction
• Other drugs taken in the past 3
months prior to the reaction
Break down
reporting
45. Mitul Jadeja - EURODIS PV training
Use this crib sheet to help complete a Yellow Card if you suspect an
adverse drug reaction (ADR)
Adverse
Drug
Reaction
suspected?
www.mhra.gov.uk/yellowcard or App
Paper Yellow Cards available from:
back of the BNF, MHRA Commission on Medicines
(CHM) free phone: 0800 731 6789, ABPI medicines
compendium or MIMS Companion
Report it via a Yellow Card
The minimum information
needed for completing a
Yellow Card:
Additional information to supply
(this information helps assess the Yellow
Card):
Names of the medicine(s)
suspected to have caused the
reaction
Details of the suspect medicine(s) if available. For
example;
dose
start and stop dates
route of administration
Batch numbers especially for vaccines,
biosimilars and biological medicines
action taken with the drug - stopped, dose
change, restarted, none etc.
Suspected reaction(s)
Details of the reactions if available:
a brief description of reaction
diagnosis if relevant
start and stop dates of reaction
seriousness (use tick boxes on Yellow Card)
treatment given
reaction outcome
At least one patient identifier:
Sex
Age
Weight
initials
local identifier
All should be completed if available
Any additional information you have:
relevant medical history
test results
other drugs taken in the last 3 months
if any rechallenge was performed
If it is a congenital abnormality, state all other
drugs taken during pregnancy and date of last
menstrual period
If no further information is available, please indicate
this on the Yellow Card
Reporter details:
Include your name, qualification
and full address
Do you suspect an adverse drug reaction?
Serious
reaction?
Involves a
medicine on
additional
monitoring
(▼)?
Unlisted
reaction
in product
information
Unsure
to report?
No
Involves a
child or
elderly
person?
ReportYes
No
No
No
No
ReportYes
ReportYes
ReportYes
ReportYes
Other PDFs with
info for patients on
the Yellow Card
website on what to
report and why –
applicable for all
reporting systems.
46. Mitul Jadeja - EURODIS PV training
Case studies are important
[Image from Arch Dis Child Fetal Neonatal Ed 2012;97:F64. doi:10.1136/adc.2011.215145]
• chlorhexidine antiseptic solution associated with
chemical burns
• review of OTC liquid codeine medicines for cough in children
• review of over-the-counter cough and cold medicines for use
in children
• oral iron products associated with hypersensitivity (allergic
type reactions)
• skin reactions associated with the use of aqueous cream in
children with eczema
• https://www.gov.uk/government/uploads/system/uploads/atta
chment_data/file/396811/Contribution_of_Yellow_Cards_to_i
dentifying_safety_issues.pdf
49. Mitul Jadeja - EURODIS PV training
Mobile Applications
• Secure – no
ADRs stored on
device
• View numbers of
YCs
• Simple to submit
updates to reports
• Allows viewing of
previous reports
via the app
• WEB-RADR
Mitul Jadeja - SCOPE EURODIS PV training
50. Mitul Jadeja - EURODIS PV training
Channels
and
Tactics
highlighted
Channels
and
Tactics
highlighted
Hungary
Interactive
presentations
Hungary
Interactive
presentations
Bulgaria
posters and
arguments
list
Bulgaria
posters and
arguments
list
Croatia
Radio &
Theatre
Croatia
Radio &
Theatre
Denmark
Learning
website with
videos
Denmark
Learning
website with
videos
Czech
Republic
Videos,
postcards &
posters
Czech
Republic
Videos,
postcards &
posters
Latvia
PV book
Latvia
PV book
United
Kingdom
online forum
for doctors
use of social
media and
digital banners
United
Kingdom
online forum
for doctors
use of social
media and
digital banners
Ireland
Congress
and special
award
Ireland
Congress
and special
award
Most successful campaigns
featured:
• forming long term sustainable
partnerships
• engagement with HCPs in a
familiar environment
• Distributed & online materials
• Press & media coverage
• Use of various forms of
collateral and channels
51. After these medicines, Doctor, I feel
better already but my wife says I have
a strange colour recently.
Hepatotoxicity is a possible side effect
of many medications
59. Mitul Jadeja - EURODIS PV training
• Leverage
content across
platforms to
boost efficiency
& avoid content
duplication
60. Mitul Jadeja - EURODIS PV training
Take home messages
• Be proactive to promote and report suspected ADRs with patients
and your members. Social media is a powerful medium, use the
ready to use materials available to support tackle underreporting and
raising awareness.
• Keep is simple, short and specific
• Access regulatory outputs to engage with NCAs/patients
• Don’t hesitate to ask/offer support/guidance on materials /decisions
that you can input/develop/tailor to meet patient needs
• Consider the engagement pyramid – how can you help NCAs
understand your stakeholders and help shape direction of work and
decision making
61. Mitul Jadeja - EURODIS PV training
Reflections…
• When did you last discuss side effects with members?
• Have you surveyed them? What are their awareness levels?
▼? Have you done a SWOT or GAP analysis?
• How many side effects have you reported? How was the
experience? Did you feedback?
• What can you do to promote reporting?
• What are your messages?
• Which tools will you use? Are they the most effective?
• How will you stay up to date with latest info?
• How will you measure success?
• Social media – how active are you?
• Will you support future campaigns? Are you a patient QPPV?
Contacted your regulator?
• What else do you need to facilitate your important role in
patient safety?
62. Mitul Jadeja - EURODIS PV training
Thank you and questions?
63. Crown copyright 2018
• The views of the author are his own.
• The materials featured within these MHRA presentation notes and delegate pack are subject to Crown copyright
protection for this event. Any other copy or use of Crown copyright materials featured in this presentation, in any form or
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