Download - Methods in Pv
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Methods to study medicinesafety problems
Mary R CouperQuality Assurance and Safety of Medicines
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METHODS TO STUDY DRUG SAFETY PROBLEMS
animal experiments
clinical trials
epidemiological methods
spontaneous reporting Cohort event monitoring
Other epidemiological methodsPhase IV studies usually
carried out by pharmaceutical
industry
Case series
Registers
Record linkages
Meta- analysis
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Spontaneous reporting
Principle: The alert health professional connects anundesirable medical event with medicine exposure
Suspicion
Report is sent to central database for analysis
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Spontaneous reporting - advantages
large population all medicines
hospital and out-patient care
long perspective
patient analyses possible
inexpensive
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Spontaneous reporting - disadvantages
Underreporting
Poor quality of reports
No denominator data
Reporting varies with severity of reaction
time from market introduction
promotional claims
promotion of reporting system
publicity of specific association
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Spontaneous reporting- cornerstone of PV
Eleven products recalled from UK and US during 1999-2001
Basis for recall Eight products (73%) were recalled on the basis of spontaneous
reports Two products (18%) recalled on basis of RCTs
Two products (18%) recalled on basis of comparativeobservational studies
Ref. Drug Safety 2006: An assessment of the publicly disseminated evidence of safety used indecisions to withdraw medicinal products from the UK and US markets. Clarke A, Deeks JJ,Shakir SA.
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Cohort Event Monitoring
Cohort event monitoring (CEM) is aprospective, observational, cohort study
of adverse events associated with one
or more medicines.
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Basic CEM principles
Enroll a cohort of patients
Actively pursue adverse events
(Hot pursuit)
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DJ Finney 1965
The purpose of monitoring is to ensure that observationson a large number of persons who receive a new drug are
collated and used effectively; only so can a warning of any
untoward consequences be given as early as possible.
.a reporter is not required to judge whether an event
was drug-induced, though he may usefully express an
opinion.
a skilled medical scrutineer at the centre becomessuspicious much earlier than anyone else.
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The objectives of CEM
Characterize known reactions
Detect signals of unrecognized reactions
Interactions with
Other medicines
Complementary and alternative medicines
Foods
Identify risk factors so that they can be avoided
Age Duration of therapy
Gender Concomitant disease
Dose Concomitant therapy
Assess safety in pregnancy & lactation
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Cohort
PopulationSample
Exposed Outcome
Time
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The objectives
Detect inefficacy, which might be due to Faulty administration
Poor storage conditions
Out of date
Poor quality product Counterfeit
Interactions
Drug utilization
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Reporting requirements
All new events even if common & minor
Change in a pre-existing condition
Abnormal changes in laboratory tests
Accidents
All deaths with date & cause
Possible interactions
NB alcohol, OCs, CAMs
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Non-serious events
May indicate serious problem
May affect compliance nausea
Extreme lethargy
diarrhoea
May be more important than serious reactions
Recording all events is easier than being selective
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Special follow-ups
Pregnancies
Deaths
Treatment failures
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Pregnancies
Pregnant women followed up
Women of child-bearing age
Pregnancy test or
follow-up
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Death
Procedure for follow-up with specific form
Accurate timing
Try & establish cause
Laboratory results
Autopsy
Confirm drug use
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Lack of effect
Adherence to instructions
Did not retain medication vomiting
diarrhoea
Incorrect diagnosis
Batch
Quality / counterfeit issue?
Resistance issue?
Specific enquiry if numbers of cases
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Publications on CEM
Pharmacovigilance for antiretrovirals in resource-poorcountries. Geneva 2007
Manual for pharmacovigilance of antimalarials in press