Download Overview of Draft Pharmacovigilance Protocol

Some Perspectives on a
Draft Pharmacovigilance
Protocol-reference to
HIV/AIDS
I Ralph Edwards
Identifying ADRs in Africa – Special
Challenges: general
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Limited access to health services
Limited diagnostic capabilities
Over-burdened health care system & staff
Significant resource restraints
Communication barriers
Identifying ADRs in Africa – Special Challenges:
HIV/AIDS
• Patients need to continue drugs
– ADRs common and troublesome
• Need to treat ADRs
• Combinations of drugs
– Which drug?
• Disease and complications and ADRs
affect multiple overlapping body
systems
Introduction
• Much information and experience in
USA/EU, but
– Different drug combinations used
– Population and disease burden varies
• Inadequate infrastructure in place in
many 3x5 roll-out countries to monitor
safety
Definition:
Adverse Event vs. Adverse Reaction
• Adverse Drug Reaction
– A noxious and unintended response to a medicine
which occurs at doses normally used in man for
treatment, prophylaxis, diagnosis or
modification of physiological function.
• Adverse Event:
– untoward medical occurrence which does not
necessarily have to have a causal relationship
with the treatment
Adverse Drug Reaction vs. Adverse Event
Adverse Event
Diseases
Genetics
Diet
Other
factors
Adverse Drug Reaction
(event attributed to drug)
All Spontaneous
reports
Other Drugs
Compliance
Events not attributed to drug
Environment
Definition:
Serious Adverse Event
• Any untoward medical occurrence that at any
dose results in:
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Death
Is life-threatening
Requires or prolongs patient hospitalisation
Results in permanent disability/incapacity or is
A congenital anomaly/ birth defect
Other medically significant event (e.g. blood
dyscrasias, seizures)
– Does not include NON-serious events that have
the POTENTIAL to be SERIOUS if allowed to
progress further, nor SEVERE events
Objectives of a Basic System
• Signal detection for concerns about the safety of
drugs
• Assessment of signals to evaluate:
– causality,
– clinical relevance,
– frequency and distribution in certain population groups
• Communication and recommendations to authorities
and public
• Appropriate response/action
– in terms of drug registration, drug use and/or training and
education for professionals and the public
• Measurement of outcome of response/action taken
– (e.g. reduction in risk of signal, improved drug use, or
improved outcome of patients with ADR)
The pharmacovigilance process
Follow up
Case reports
Action
Case database
Communication
Signal
detection
Signal
analysis
Why Monitor ALL drugs?
• Create an awareness of safety issues and drugs
• To encourage health professionals to share concerns
about drugs
• To determine the concerns health professionals have
over drugs and their best use
– Including interactions
• To react to with helpful information to improve
therapy
• Minimise undue concern about safety of therapies
known to cause ADRs
– Eg. Anti-retrovirals
• Allow for comparison of reporting rates among
different therapeutic classes of medicines
Elements of the Basic system
• Possible general system:
– Peripheral health facilities
• (spontaneous reporting of drugs used in general medical
practice)
– Tertiary care facilities and ADR Centre
• (Spontaneous reporting and SAEs investigated and
intensive monitoring programmes. Special investigations)
– Antenatal and delivery clinics
• (Pregnancy-related SAE’s and congenital anomalies
reported)
– Public health Programmes
• HIV/AIDS, Malaria etc.
Peripheral Health Care Facilities:
E.g. health posts, clinics, outreach centres, dispensaries, outpatient
departments
• Proper prescribing, counseling and administration
of meds
– Inform patients to return in case of further or ongoing
illness
– Counsel patients on how to take meds
– 1 hour observation post-medication
• Completion of SAE form in the event of suspected
reaction
• Send form to district/state/national level
coordinator (depending on infrastructure)
• Patients referral to hospital if necessary (with
referral note informing of suspected ADR)
• Management of non-serious reactions
Evaluation/Investigation Team
• General or special or geographical (??)
– May be comprised of only 1 person
• Weekly review of all reports received
– Follow-up all/specific SAEs
• Home and facility visit if warranted
• Return to facility within 2 weeks for investigation
• Review ADR forms and Investigation Team
report forms
• Aggregation into monthly report
• Aggregates and individual reports
forwarded to national co-ordinator
Secondary/Tertiary Care Facilities
E.g. Hospitals, health centres (others?)
• Investigate any patient attending
tertiary care hospitals due to suspected
ADR (self-reported, detected in hospital
or referred from peripheral health
workers) should be investigated
• Intensive monitoring in specifically
selected facilities
– Event monitoring and epidemiological studies
Antenatal Clinics and Delivery Services
• Report congenital anomalies using SAE
reporting form
Detection of serious drug reactions
intensive
(if abnormal lab tests,
eg agranulocytosis,
interview patient for
detailed history)
Case-finding
or cohort
HOSPITAL
Laboratory and clinical
investigations
HEALTH CENTERS
PRIVATE CLINICS
Generic form
Follow-up
with detailed
report and
causality
rating,
spontaneous
DISPENSARIES
Shops, traditional healers, other health professionals
Roles and Responsibilities
• Establish roles and responsibilities of
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Patient
Clinic staff
Traditional Healers and other informal providers
District/state/national investigation team
National pharmacovigilance co-ordinator
Expert safety review panel
Malaria control programme
Drug regulatory authority
Media
International agencies (WHO, UMC, etc)
Some participants!
Health care
Regulators
National
Centres
Medical
media
WHO
Pharma
industry
Health care
Regulators/
National
Centres
Prescription
Decision to
treat
WHO
ADR
Benefit -harm
assessment
Collection
Decision to
report
Causality
assessment
Reporting
Diagnosis
Regulator’s
decision
Increased
knowledge
Medical
media
Effectiveness risk assessment
Pharma
industry
Storage
Screening
Signal
detection
Discussions
company regulator
Analysis of all
evidence
Company
decision
Preliminary
analysis
Further
study
Process
Evaluation/decision
External
communication point
From data to signal analysis:
international
Follow up
National case reports
WHO database
UMC Signal
detection
Action
Communication
Signal
analysis
The Importance of Denominators
• Denominator: estimated figure of drug use
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for estimating frequency of events
• Comparisons between drugs difficult and
VERY problematic without rates
– Often use a comparator/control drug within the
system to determine whether lack of signals due to
underreporting or real absence of signal
Examples of Denominators
• Drug procurement figures from central medical
stores of MOH
• Drug distribution data from EDPs, national drug
suppliers/distributors, or manufacturers
• Drug records at importation from customs
• Notification reports from disease surveillance
programmes
– ?e.g. HIV/AIDS
• Drug procurement records from wholesalers in
private sector
• Supplementary drug surveys (e.g. treatment seeking
behaviour, drug utilisation, or surveys of drug
vendors.)
Adopting and Adapting – the forms
• ADR report form
• Evaluation and follow-up form
• Special investigations
– Public health programmes e.g. HIV/AIDS
– Congenital anomaly registers
– Etc.
• Study protocols
Communication: General
• All reports must be acknowledged
– Reporters must feel a valued part of the
system
• Useful feedback must be given
– Specific to the case if necessary
– General, in the form of periodic reports
Communication: HIV AIDS
• Must allow treating health professionals
best information on effectiveness v.
risks
– Globally and in own population
• Give them, and patients, knowledge and
confidence to continue therapy in spite
of some ADRs
• Give information on best avoidance,
minimisation, and treatments for ADRs
Issues for discussion and consideration (I)
• Is this system feasible in your country?
– Should it be modified/simplified?
• When should you be encouraging reporting of events or
reactions
• Should you encourage reporting of serious
events/reactions only or include non-serious as well?
– (This draft does not discourage non-serious reports)
• Based on resources, size of country and nature of public
health structures– is a special investigation team needed?
– Could a ‘generic’ national-level or state-level investigation team
suffice?
• Can the proposed reporting flow be adapted to your
country setting?
Issues for discussion and consideration (II)
• Should the forms be printed in single or duplicate? If
duplicate who will each copy go to?
• What should be the timelines for submitting initial
reports, investigations reports, aggregate reports? And to
whom
– supervisor, national coordinator, special investigation team etc.
• Which reports to be investigated? All suspected ADRs,
clusters ? Unexpected? Unusual? Significantly affecting
compliance?
Issues for discussion and consideration (III)
• Consider the functions and activities of each
individual/organisation in your proposed reporting
flow
• What would be an accurate denominator for drug use
for HIV/AIDS treatments and a comparator/s
• What do you think are the critical success factors to
achieve the system and its objectives?
• How can these critical success factors be achieved in
your country?
Critical Success Factors
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Literacy of reporters
Clearly defined responsibilities
Adequate training and education
Public awareness of the new medicine
Public awareness on reporting safety problems of all medicines
Awareness of pharmacovigilance system within informal sector
– Community & religious leaders, shopkeepers, traditional healers,
community health workers and school teachers
• Quality control of laboratories
• Open communication between public, health care providers and
policy makers
– Judicious and pro-active use of the media, professional and general
• Presence of national coordinator/s