Download 1294-Dodoo-_b

Pharmacovigilance: opportunities
for active surveillance and other
fanciful stuff
Dodoo ANO, Pal S (WHO-HQ), Olsson S, Lindquist, M., Edward IR (all of UMC)
Director, WHO Collaborating Centre for Advocacy and Training in
Pharmacovigilance, University of Ghana Medical School, Accra, Ghana
[email protected] // [email protected]
With some diagrams/illustrations from Geraldine Hill, CARM/IMMP
New Zealand
The issues
• There is the need to collect real-life safety
information on all medicines used in all countries
• Because
– Pre-licensure clinical studies are of short-duration, limited in
extent and exclude several groups of people including typically
the elderly, children, pregnant women, lactating mothers
– Global health initiatives have helped to expand access to life
saving medicines for conditions like HIV/AIDS, malaria, TB; BUT
• These medicines are being used in countries with little or no systems for
safety monitoring
• Some of these medicines or combinations are new and are being used for
the first time ever – no experience of use anywhere else
• Safety issues can compromise public health programmes and
interventions
In short ....
• The global community has very little information on the
safety profiles of medicines deployed for priority
conditions
• Genetics (pharmacogenetics), differences in healthcare
practices, endemic diseases and other considerations e.g.
malnutrition can all have an effect on medicine safety
• Countries could rely on the classical method of
pharmacovigilance in most countries - spontaneous
reporting
• Or countries can develop and/or utilise newer methods
to address national safety issues bearing in mind the well
known limitations of spontaneous reporting
Spontaneous Reporting
Spontaneous report (ICSR - individual case safety report)
‘an unsolicited communication by healthcare professionals
or consumers that describes one or more adverse drug
reactions in a patient who was given one or more
medicinal products and that does not derive from a study
or any organised data collection scheme’
Adverse drug reaction
‘a response to a medicine which is noxious and
unintended, and which occurs at doses normally used
in man’ (WHO)
Spontaneous Reporting
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 ADR report
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Spontaneous Reporting
Pros
Cons
Detection of signals of new, rare or
serious ADRs
Only suspected ADRs reported
Most commonly used method
Easiest method to establish
Relatively inexpensive
Least labour intensive
Continual safety monitoring of a
product
Covers all medicines
Under-reporting* so data incomplete
Reporting bias**
Lack of denominator†
Unable to accurately assess risk, risk
factors or between drug
comparisons‡ §
Poor at detecting delayed ADRs
Deaths poorly reported
Targeted Spontaneous Reporting
Targeted spontaneous report (‘targeted ICSR’)
‘a spontaneous report from a healthcare
professional or consumer within a defined
cohort that describes one or more adverse
drug reactions in a patient who was given
one or more medicinal products’
Targetted Spontaneous Reports
(of adverse events and reactions)
Targeted Spontaneous Reporting
Pros
Cons
Still relatively inexpensive, simpler
and less labour intensive c.f. CEM
Only suspected ADRs reported
Principles similar to SR, hence
familiarity
Higher reporting rates than SR*
Denominator known so incidence of
known or suspected ADRs may be
determined
May encourage spontaneous
reporting
Some reporting bias remains, but less
than SR
Reporting incomplete so numerator
incomplete; assessment of risk not
reliable
Active Surveillance e.g. Cohort Event Monitoring
• “Hot pursuit”
• Identify, recruit and follow-up cohort of
patients who receive specified medicines e.g.
antimalarials, anti-retrovirals
– Document demographic & drug information, mode of
diagnosis
– Solicit information on adverse events during follow-up
visits
• Usually once for anti-malarials and continuously for anti-retrovirals
• Phone follow-up where possible
• Provides rapid safety information and denominator
Cohort Event Monitoring
Adverse event report
‘a solicited communication by healthcare professionals for a
patient within a defined cohort that describes one or more
adverse events in a patient who was given one or more
actively monitored medicines’ (G. Hill)
Adverse event
Any new clinical experience (favourable or
unfavourable) that is worthy of a record in the
patient’s file, regardless of its severity and without
judgement on its causality (D. Coulter)
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Spontaneous Reporting
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Targeted Spontaneous Reporting  
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CEM
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Cohort Event Monitoring
Pros
Cons
Early detection of signals of
unsuspected ADRs
More labour intensive than SR or TSR
More costly
Denominator information allows
incidence rates of ADRs to be
calculated
Much data collected most of which
represents ‘background noise’
Near complete profile of AEs/ADRs
for medicine of interest
New to health professionals and PV
Centres
Assessment of risk; characterises risk
factors; between drug comparisons
Training required
Pregnancy outcomes
Deaths recorded
LTFU may be substantial and needs to
be actively managed
Several mechanisms for collecting
information during follow-up
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Home visits
Diary cards
Telephones
Cell phones
SMS
Collecting event information?
Diary/AE Card – Outer Fold
Diary/AE Card – Inner Fold
Injection
Site Abscess
Date:
Social Media and SMS for
Pharmacovigilance
“Hello. My name is John twitter. I have
an ADR that I intend to report to
pharmacist facebook or that failing to
Dr You Tube . …”
Conventional social media
Usage and Impact
 In the US, 22% of all online time or one in every
4.5 minutes is spent on social networking; with
74% of internet consumers using social networks
(http://blog.nielsen.com/nielsenwire/global/soci
al-media-accounts-for-22-percent-of-timeonline/)
 One in four people aged 65yrs and above now
join social networking
(http://www.cbsnews.com/stories/2010/11/15/n
ational/main7055992.shtml)
Usage and Impact
 Facebook recorded 750 million users in June 2011
and would be the largest third if it were a country
(http://techcrunch.com/2011/06/23/facebook-750million-users/
,http://www.socialnomics.net/category/statistics/).
 In the US facebook tops Google for weekly traffic
(http://www.socialnomics.net/category/statistics/).
 93% of business use social media for marketing.
(http://en.wikipedia.org/wiki/Social_media)
Guidance to industry and
pharmacovigilance (EMA Vol. 9a)
• 4.3.3 Information on Adverse Reactions from the
Internet
• The Marketing Authorization Holder should regularly screen websites
under their management or responsibility, for potential reports on adverse
reactions. The Marketing Authorization Holder is not expected to screen
external websites for information of adverse reactions. However if a
Marketing Authorization Holder becomes aware of an adverse reaction on
any other website the Marketing Authorization Holder should review the
case and determine whether it should be reported in expedited manner in
accordance with Chapter I.4, Sections 3.1 and 3.5
Vol. 9a (continued)
• The Marketing Authorization Holder should consider utilizing
their websites to facilitate adverse reaction collection, e.g. by
providing adverse reaction forms for reporting or by providing
appropriate contact details for direct communication. In
relation to such reported adverse reactions, identifiability of
the reporter and Patient refers to the existence of actual
New EC PV regulation (2010/84/EU)
• Article 102
• The Member States shall:
• (a) take all appropriate measures to encourage patients, doctors,
pharmacists and other healthcare professionals to report
suspected adverse reactions to the national competent authority;
for these tasks, organizations representing consumers, patients and
healthcare professionals may be involved as appropriate;
• (b) facilitate patient reporting through the provision of alternative
reporting formats in addition to web-based formats;
• (c) take all appropriate measures to obtain accurate and verifiable
data for the scientific evaluation of suspected adverse reaction
reports;
WHO-CC Ghana and Tigo Collaboration
• Simple SMS system for ADR collection
– Patient gets enrolled at point of dispensing
• Demographics, initials, gender, medicine (name, dose,
route) taken
• SMS to server and to patient (serves as carrot: personal
patient medication record)
– Second carrot: patient gets reminders to take medicine if
patient so requests
• PV centre able to use the data in the server to either
request manually ADR information or to send SMS
soliciting for ADRs
• System finalised and roll out just starting.....
Conclusions
• Mechanisms exist for collecting safety
information in all countries including resource
limited countries
• Active surveillance is key when new products
are deployed
• Newer technologies hold great promise