76
Kia Ora!
Kia Ora!
TanzaniaTanzaniaNovember 2009November 2009
Cohort Event MonitoringCohort Event MonitoringPrescription event monitoring (PEM)Prescription event monitoring (PEM)
Dr. David CoulterDr. David Coulterformerly Research Associate Professorformerly Research Associate Professor
Intensive Medicines Monitoring ProgrammeIntensive Medicines Monitoring Programme& Head NZ Pharmacovigilance Centre& Head NZ Pharmacovigilance Centre
Dr. Geraldine HillDr. Geraldine HillTeaching Fellow, University of Otago Medical School, Teaching Fellow, University of Otago Medical School,
Dunedin, New ZealandDunedin, New Zealand(formerly Research Fellow(formerly Research Fellow
Intensive Medicines Monitoring Programme)Intensive Medicines Monitoring Programme)
33
CEM worldwideCEM worldwide
NZ Intensive Medicines Monitoring NZ Intensive Medicines Monitoring Programme (IMMP), NZ, 1977Programme (IMMP), NZ, 1977
Drug Safety Research Unit (PEM), Drug Safety Research Unit (PEM), Southampton, UK, 1980Southampton, UK, 1980
Tanzania Tanzania CEM of anti-malarials CEM of anti-malarials
NigeriaNigeria
44
Plan of presentationPlan of presentation
ObjectivesObjectivesWhat results can you get?What results can you get?Examples and methods from the NZ Intensive Medicines Examples and methods from the NZ Intensive Medicines
Monitoring Programme (IMMP)Monitoring Programme (IMMP)
How do we get them?How do we get them?
Observations & commentsObservations & comments
55
The objectives of CEMThe objectives of CEM1.1. Characterise known reactionsCharacterise known reactions
– Mean ageMean age– GenderGender– Mean doseMean dose– Treatment durationTreatment duration– Time to onsetTime to onset– Seriousness profileSeriousness profile– IncidenceIncidence– OutcomesOutcomes– Effect on treatment (% withdrawals)Effect on treatment (% withdrawals)– Part of syndrome?Part of syndrome?
66
The objectives of CEMThe objectives of CEM2.2. Detect signals of unrecognised reactionsDetect signals of unrecognised reactions
3.3. Interactions withInteractions withOther medicinesOther medicinesComplementary and alternative medicinesComplementary and alternative medicinesFoodsFoods
4.4. Identify risk factors so that they can be avoidedIdentify risk factors so that they can be avoidedAgeAge Duration of therapyDuration of therapyGenderGender Concomitant diseaseConcomitant diseaseDoseDose Concomitant therapyConcomitant therapy
77
The objectives of CEMThe objectives of CEM
5.5. Assess safety in pregnancy & lactationAssess safety in pregnancy & lactation
6.6. Estimate risk (including comparative)Estimate risk (including comparative)
7.7. Provide evidence for effective risk Provide evidence for effective risk managementmanagement
Safer prescribingSafer prescribingBenefit / harm assessmentBenefit / harm assessmentRegulatory changesRegulatory changes
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The objectives of CEMThe objectives of CEM
8.8. Detect inefficacy, which might be due toDetect inefficacy, which might be due toFaulty administrationFaulty administrationPoor storage conditionsPoor storage conditionsOut of dateOut of datePoor quality productPoor quality productCounterfeit Counterfeit InteractionsInteractions
99
The objectives of CEMThe objectives of CEM
9.9. Hypothesis generationHypothesis generation
10.10. Cohorts for studyCohorts for study
1010
The objectivesThe objectives
Achieve Achieve maximum maximum benefitbenefit, , least harmleast harm for for
patientspatients
1111
What results can you get?What results can you get?
1212
COX-2 inhibitorsCOX-2 inhibitorscelecoxib, rofecoxibcelecoxib, rofecoxib
Preliminary monitoring Preliminary monitoring datadata
1313
The following will be The following will be summarisedsummarised
Cohort description & drug utilisationCohort description & drug utilisation
Preliminary events dataPreliminary events data
Preliminary review of deathsPreliminary review of deaths
1414
IMMP ProcessIMMP ProcessPrescription
Patient and Prescription details
Follow-up questionnairesEvent information
Cohort data Relationship
assessment
NZHIS
1515
CohortCohort
Prescriptions Patients
Celecoxib 98,975 32,630
Rofecoxib 52,874 26,666
1616
Profile of Ages at First Prescription
213543
1477
3325
5827 5969
6552
3601
503468
945
1939
3426
4704
4254 4297
2289
280
0
5
10
15
20
25
< 20 20-30 30-39 40-49 50-59 60-69 70-79 80-89 90 plus
% o
f tot
al k
now
n ag
es
Celecoxib Rofecoxib
1717
IMMP example –COX-2IMMP example –COX-2AgeAge CelecoxibCelecoxib RofecoxibRofecoxib
MeanMean 6363 5858
ModeMode 5959 5353
<40 years<40 years 6.9%6.9% 12.6%12.6%Highly significantHighly significant
70+ years70+ years 32.7%32.7% 25.7%25.7%Highly significantHighly significant
1818
Gender and termGender and term
CelecoxibCelecoxib RofecoxibRofecoxib
WomenWomen 61.6%61.6% 60.5%60.5%
Short termShort term 6879 (21%)6879 (21%) 9843 (37%)9843 (37%)
1919
Rofecoxib doseRofecoxib dose
12.5 11,695 28.3
25 26,027 63.0
37.5 36 0.1
50 3,546 8.6
mg/day No. %
2020
Celecoxib dose mg/no./%Celecoxib dose mg/no./%100 6,622 8.1 200 65,591 80.5 300 274 0.3 400 8,927 11.0 600 46 800 30
2121
IMMP ProcessIMMP ProcessPrescription
Patient and Prescription details
Follow-up questionnairesEvent information
Cohort data Relationship
assessment
NZHIS
2222
Indications for useIndications for use((0r type/seriousness of malaria0r type/seriousness of malaria))
CelecoxibCelecoxibNo. %No. %
RofecoxibRofecoxibNo. %No. %
DifferenceDifferenceChi-squareChi-square
PatientsPatients 6,2006,200 4,5364,536InflammatoryInflammatory 211 (3.4)211 (3.4) 129 (2.8)129 (2.8) P>0.05P>0.05OsteoarthritisOsteoarthritis 1805 (29)1805 (29) 775 (17)775 (17) P<0.0001P<0.0001MusculoskelMusculoskel 1668 (27)1668 (27) 1105 (24)1105 (24) P<0.01P<0.01Other painOther pain 2479 (40)2479 (40) 2495 (55)2495 (55) P<0.0001P<0.0001
2323
Baseline information 1Baseline information 1QuestionsQuestions
1.1. Current Acid Related DisorderCurrent Acid Related Disorder2.2. Past ARDPast ARD3.3. NSAID exposure NSAID exposure
• Past GI problems Past GI problems • Direct switch to COX-2Direct switch to COX-2• Concurrent aspirinConcurrent aspirin
4.4. Past cardiovascular diseasePast cardiovascular disease• Hypertension / Heart failureHypertension / Heart failure• MI / AnginaMI / Angina• Dysrhythmia / Stroke - TIADysrhythmia / Stroke - TIA
2424
Baseline information 2Baseline information 2
Questionnaire response rateQuestionnaire response rate CelecoxibCelecoxib: number sent 4635 : number sent 4635
No. returned with information 3985 No. returned with information 3985 (91%)(91%)
RofecoxibRofecoxib: number sent 3050 : number sent 3050 No. returned with information 2725 No. returned with information 2725
(89%)(89%)
2525
Baseline information 3Baseline information 3No. & % of positive responses to questionNo. & % of positive responses to question
CELCEL ROFROF Rate ratioRate ratio(95% CI)(95% CI)
ARDARD 2281 2281 (68%)(68%)
1341 1341 (60%)(60%)
1.4 1.4 (1.27-1.58)(1.27-1.58)
NSAID/ARDNSAID/ARD 2136 2136 (62%)(62%)
1199 1199 (54%)(54%)
1.41.4(1.28-1.59)(1.28-1.59)
SwitchSwitch 1345 1345 (36%)(36%)
824 824 (34%)(34%)
1.91.9(0.98-1.21)(0.98-1.21)
AspirinAspirin 352 352 (9.3%)(9.3%)
173 (6.9%)173 (6.9%) 1.41.4(1.15-1.69)(1.15-1.69)
CardiovascCardiovasc 1361 1361 (36%)(36%)
797 797 (31%)(31%)
1.21.2(1.11-1.38)(1.11-1.38)
2626
Baseline information 4Baseline information 4Cardiovascular diseaseCardiovascular disease
CelecoxibCelecoxib RofecoxibRofecoxib Rate ratioRate ratio(95% CI)(95% CI)
HypertensionHypertension 843 (22%)843 (22%) 498 (19%)498 (19%) 1.11.1(1.04-1.26)(1.04-1.26)
MI/anginaMI/angina 547 (14%)547 (14%) 298 (12%)298 (12%) 1.21.2(1.09-1.42)(1.09-1.42)
HFHF 206 (5.4%)206 (5.4%) 115 (4.5%)115 (4.5%) 1.21.2(0.97-1.51)(0.97-1.51)
DysrhythmiaDysrhythmia 141 (3.7%)141 (3.7%) 86 (3.3%)86 (3.3%) 1.11.1(0.85-1.44)(0.85-1.44)
Stroke/TIAStroke/TIA 40 (1.0%)40 (1.0%) 17 (0.7%)17 (0.7%) 1.61.6(0.90-2.80)(0.90-2.80)
2727
The eventsThe events
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Profile of Events - Celecoxib and Rofecoxib n=1714 n=982
64
2222
156
103
7858
123532
8
44
1932
293301
22
273
33
4050
5139
28
122121
912
28
123
17
179
5
198
181
13
0
5
10
15
20
25
System Organ Class
Perc
enta
ge o
f To
tal E
vent
s
Celecoxib Rofecoxib
2929
Most common events 1Most common events 1rates /1000 patientsrates /1000 patients
CelecoxibCelecoxib RofecoxibRofecoxib
EventEvent No.No. RateRate No. No. RateRate RRRR
ARDARD 129129 3.43.4 8989 3.33.3 NSNS
RashRash 8686 2.62.6 3030 1.11.1 2.3 (1.6-3.6)2.3 (1.6-3.6)
HFHF 7474 2.32.3 5555 2.12.1 NSNS
IHDIHD 5757 1.81.8 3838 1.41.4 NSNS
3030
Most common events 2Most common events 2CelecoxibCelecoxib RofecoxibRofecoxib
EventEvent No.No. RateRate No. No. RateRate RRRR
LRTILRTI 5656 1.71.7 2929 1.11.1 1.6 1.6 (1.0-2.5)(1.0-2.5)
DysrhythmiasDysrhythmias 4949 1.51.5 1919 0.70.7 2.1 2.1 (1.2-3.6)(1.2-3.6)
AngioedemaAngioedema 4848 1.51.5 1414 0.50.5 2.8 2.8 (1.6-5.1)(1.6-5.1)
StrokeStroke 3737 1.11.1 1818 0.70.7 NSNS
3131
Most common events 3Most common events 3CelecoxibCelecoxib RofecoxibRofecoxib
EventEvent NoNo RateRate No. No. RateRate RRRRDiarrhoeaDiarrhoea 3636 1.11.1 1717 0.60.6 NSNSAsthmaAsthma 3434 1.01.0 1313 0.50.5 2.1 (1.1-4.1)2.1 (1.1-4.1)
RFRF 3333 1.01.0 2828 1.11.1 NSNS
VomitingVomiting 3333 1.01.0 3434 1.31.3 NSNS
HTHT 1313 0.30.3 2828 1.11.1 2.6 (1.4-5.0)2.6 (1.4-5.0)
3232
Signals identified 1Signals identified 1CoughingCoughingVisual field defect / temp blindnessVisual field defect / temp blindnessAcute psychiatric eventsAcute psychiatric eventsPancreatitisPancreatitisHepatotoxicityHepatotoxicityPsoriasisPsoriasisAcute urinary retentionAcute urinary retention
3333
Signals 2Signals 2Mouth ulcerationMouth ulcerationLower bowel effectsLower bowel effectsCardiac dysrhythmiasCardiac dysrhythmiasCardiac arrestCardiac arrestMyocardial infarction / strokeMyocardial infarction / strokeAnaphylaxisAnaphylaxisSerious skin infectionSerious skin infectionAcute labyrinthitisAcute labyrinthitis
3434
Signals 3Signals 3InteractionsInteractions
Tricyclics causing arrhythmiasTricyclics causing arrhythmiasWarfarin causing increased INR Warfarin causing increased INR (rofecoxib)(rofecoxib)
3535
DeathsDeathsCauses by SOC Causes by SOC (% of total deaths)(% of total deaths)
CelecoxibCelecoxib No. (%)No. (%) RofecoxibRofecoxib No. (%)No. (%)All deathsAll deaths CausalCausal All deathsAll deaths CausalCausal
CirculatoryCirculatory 116 (40)116 (40) 34 34 (11.6)(11.6) 68 (38)68 (38) 23 23 (12.9)(12.9)MalignancyMalignancy 115 (39)115 (39) NilNil 92 (51)92 (51) NilNilRespiratoryRespiratory 59 (20)59 (20) NilNil 24 (13)24 (13) NilNilRenalRenal 23 (8)23 (8) 18 18 (6)(6) 8 (5)8 (5) 8 8 (5)(5)InfectionInfection 13 (4)13 (4) NilNil 11 (6)11 (6) NilNilAlimentaryAlimentary 10 (3)10 (3) 10 10 (3)(3) 8 (5)8 (5) 4 4 (2)(2)
3636
Risk factors 1Risk factors 1 by multiple logistic regressionby multiple logistic regression
Renal failureRenal failure– AgeAge– Inflammatory arthritisInflammatory arthritisHeart failureHeart failure– AgeAge– P/H heart failureP/H heart failure– Inflammatory arthritisInflammatory arthritis
3737
Risk factors 2Risk factors 2Ischaemic heart diseaseIschaemic heart disease– AgeAge– P/H of any type of heart diseaseP/H of any type of heart disease– Inflammatory arthritis (celecoxib)Inflammatory arthritis (celecoxib)Cardiac dysrhythmiasCardiac dysrhythmias– AgeAge– Past history of heart failurePast history of heart failure– Inflammatory arthritis (celecoxib)Inflammatory arthritis (celecoxib)
3838
Risk factors 3Risk factors 3Stroke / TIAStroke / TIA– AgeAge– HypertensionHypertension– Inflammatory arthritisInflammatory arthritis
3939
Did we reach the Did we reach the objectives?objectives?
4040
Study demonstratesStudy demonstratesHigh complianceHigh complianceDemographics of cohortsDemographics of cohortsBackground dataBackground data– IndicationIndication– Relevant past/current historyRelevant past/current historyPrescribing practicesPrescribing practicesEarly signal identificationEarly signal identificationSignificant eventsSignificant eventsComparative ratesComparative ratesRisk factorsRisk factors
4141
Concerns raisedConcerns raisedHigh volume of prescribingHigh volume of prescribingHigh doses of rofecoxibHigh doses of rofecoxibSubstantial prescribing to patients at Substantial prescribing to patients at high riskhigh risk– very elderlyvery elderly– history of cardiovascular diseasehistory of cardiovascular disease– history of ARDhistory of ARDApparent high death rateApparent high death rate
4242
ConcernsConcernsHigh rate of cardiovascular eventsHigh rate of cardiovascular events– Heart failureHeart failure– DysrhythmiasDysrhythmias– Prothrombotic effectsProthrombotic effects
Myocardial infarctionMyocardial infarctionStrokeStrokeRenal infarctionRenal infarction
High rate of alimentary eventsHigh rate of alimentary events
4343
How do we get results like How do we get results like this?this?
The principlesThe principles
4444
Cohort event monitoringCohort event monitoringHow is it done?How is it done?
Two PrinciplesTwo PrinciplesIdentifying patients exposed (cohort) Identifying patients exposed (cohort) - the - the denominatordenominator– as complete as possibleas complete as possibleSystematically soliciting adverse Systematically soliciting adverse EVENTSEVENTS - the - the numeratornumerator– as complete as possibleas complete as possible
4545
1. Identifying the patients1. Identifying the patientsHow can this be done?How can this be done?
The cohort of patients is established using The cohort of patients is established using the best source of usage data availablethe best source of usage data available– Dispensings (pharmacies or central records)Dispensings (pharmacies or central records)– Patient recordsPatient records
DoctorsDoctorsClinicsClinicsHospitalsHospitalsOtherOther
– Programme recordsProgramme recordsAdequate cohort (10,000 patients)Adequate cohort (10,000 patients)
4646
IMMP ProcessIMMP ProcessPrescription
Patient and Prescription details
Follow-up questionnairesEvent information
Cohort data Relationship
assessment
NZHIS
Other Rx Sources
4747
Cohort sizeCohort sizeGeneral aim 10,000 (IMMP 11,000)General aim 10,000 (IMMP 11,000)Greater numbers required to detect Greater numbers required to detect differences differences – if events naturally commonif events naturally common– for sub-group analysesfor sub-group analysesSmaller numbers still produce good dataSmaller numbers still produce good data– fluoxetine <7000fluoxetine <7000Signals can be identified / confirmed with Signals can be identified / confirmed with much smaller numbers (<1000)much smaller numbers (<1000)– eg nifedipine & eye pain eg nifedipine & eye pain
4848
2. Soliciting the events2. Soliciting the eventsHow can this be done?How can this be done?
ActivelyActively asking for the eventsasking for the events
SystematicallySystematically asking for the eventsasking for the events
4949
Soliciting the eventsSoliciting the eventsHow is it done?How is it done?
The events are collected using the best The events are collected using the best source(s) availablesource(s) available– Survey prescribers (questionnaires or other)Survey prescribers (questionnaires or other)– Survey patients (questionnaires or other)Survey patients (questionnaires or other)– Real-time recording*Real-time recording*– Telephone, or visit*Telephone, or visit*– Record searches (manual, electronic)Record searches (manual, electronic)– Registers of death or morbidityRegisters of death or morbidity– Record linkage with registers or hospital Record linkage with registers or hospital
recordsrecords– Intensified spontaneous reportingIntensified spontaneous reporting– OtherOther– SeveralSeveral
5050
IMMP ProcessIMMP ProcessPrescription
Patient and Prescription details Follow-up
questionnairesEvent information
Cohort data Relationship
assessment
NZHIS
Other Rx Sources
Other Sources
5151
Actively & systematically Actively & systematically askingasking
Ask after every treatmentAsk after every treatment
Patients in cohort checked to see that Patients in cohort checked to see that follow-up information receivedfollow-up information received
Repeat request for missed patientsRepeat request for missed patients
Make strenuous efforts to avoid missing Make strenuous efforts to avoid missing anyoneanyone
5252
Adverse event (experience)Definition (WHO)
Untoward medical occurrence
temporally associated with the use
of a medicinal product, but not
necessarily causally related
5353
It is It is EVENTEVENT monitoring monitoring
Any new clinical experience Any new clinical experience
(favourable or unfavourable) that is (favourable or unfavourable) that is
worthy of a record in the patient’s worthy of a record in the patient’s
file, regardless of its severity and file, regardless of its severity and
without judgement on its causality.without judgement on its causality.
5454
Events = reactions + incidentsEvents = reactions + incidentsReactionsReactions11 DefiniteDefinite22 ProbableProbable33 PossiblePossible
IncidentsIncidents (background noise)(background noise)4 Unlikely4 Unlikely5 Unclassified (conditional) 5 Unclassified (conditional) 6 Unassessable6 Unassessable
5555
IncidentsIncidents((MakingMaking music from the noisemusic from the noise))
Should represent background morbidityShould represent background morbidity
May contain unrecognised signalsMay contain unrecognised signals– unexpected profilesunexpected profiles
Useful for assessing reporting biasUseful for assessing reporting bias– as within-drug controlsas within-drug controls– as between-drug controlsas between-drug controls
UnmaskingUnmasking
5656
Why adverse events?Why adverse events?To identify signals of new reactionsTo identify signals of new reactions
If only known or expected adverse reactions are If only known or expected adverse reactions are reported, unexpected adverse reactions will not reported, unexpected adverse reactions will not be identifiedbe identified
It is important to identify signals, validate them, It is important to identify signals, validate them, determine the incidence, understand their determine the incidence, understand their significance and identify the risk factors as soon significance and identify the risk factors as soon as possible. as possible.
It is not logical to specify the types of events to It is not logical to specify the types of events to be recorded. Unexpected reactions cannot be be recorded. Unexpected reactions cannot be identified by recording only the known or identified by recording only the known or expected.expected.
5757
Reporting requirementsReporting requirementsAll new events even if common & minorAll new events even if common & minor
Change in a pre-existing conditionChange in a pre-existing condition
Abnormal changes in laboratory testsAbnormal changes in laboratory tests
AccidentsAccidents
All deathsAll deaths with date & cause with date & cause
Possible interactionsPossible interactions– NB alcohol, OCs, CAMsNB alcohol, OCs, CAMs
5858
Reasons for stoppingReasons for stoppingPoor compliance (adherence)Poor compliance (adherence)
No longer necessaryNo longer necessary
Change of diagnosisChange of diagnosis
Inadequate responseInadequate response
Suspected ADRSuspected ADR
DeathDeath
Lost to follow-upLost to follow-up
5959
PregnancyPregnancyRoutine questions about pregnancy and lactation Routine questions about pregnancy and lactation for all women of child bearing age –computer for all women of child bearing age –computer generatedgenerated
Pregnancy register establishedPregnancy register established
Time / period of exposure identifiedTime / period of exposure identified
Routine follow-up of all pregnancies after Routine follow-up of all pregnancies after expected delivery dateexpected delivery date
6060
Non-serious eventsNon-serious eventsMay indicate serious problemMay indicate serious problem
May affect complianceMay affect compliance– nauseanausea– Rash / pruritusRash / pruritus– DiarrhoeaDiarrhoea
May be more important than serious reactionsMay be more important than serious reactions
Recording all events is easier than being selectiveRecording all events is easier than being selective
6161
CEM in the IMMPCEM in the IMMPProspective observational cohort Prospective observational cohort studies on new drugs in normal studies on new drugs in normal clinical practiceclinical practice
Cohorts established from prescription Cohorts established from prescription data from pharmaciesdata from pharmacies
Events data mainly from Events data mainly from questionnaires sent to prescribersquestionnaires sent to prescribers
6262
ComplianceComplianceVoluntary / unpaidVoluntary / unpaidDoctors 80%Doctors 80%– Limiting factor is workloadLimiting factor is workload
Patients higherPatients higherPharmacists 93%Pharmacists 93%Good feedback essentialGood feedback essentialValue appreciatedValue appreciated
6363
‘‘Controls’Controls’Controls create an artificial situationControls create an artificial situation
The aim is a non-interventional study in normal clinical The aim is a non-interventional study in normal clinical practicepractice
Comparators are desirableComparators are desirable– not always possiblenot always possible– possibility of confoundingpossibility of confounding
A good study of a single drug A good study of a single drug – provides valuable dataprovides valuable data– has benchmark valuehas benchmark value
6464
Record linkageRecord linkageLinking databases using unique IDLinking databases using unique ID
IMMP -routine link with IMMP -routine link with – NZHIS –identify deathsNZHIS –identify deaths– Register of deaths for certified cause(s)Register of deaths for certified cause(s)
IMMP –special studiesIMMP –special studies– Suicide & antidepressantsSuicide & antidepressants– Reactions of long latency –cancer registers / hospital Reactions of long latency –cancer registers / hospital
discharge diagnosesdischarge diagnoses– Conditions of interest eg MIConditions of interest eg MI
6565
Cohort investigationsCohort investigationsPatient questionnairesPatient questionnaires– Eye pain and nifedipine / taste disturbance and captoprilEye pain and nifedipine / taste disturbance and captopril
Doctor questionnairesDoctor questionnaires– Angina and bezafibrateAngina and bezafibrate((confounding by indicationconfounding by indication))
Reactions of long latencyReactions of long latency– OmeprazoleOmeprazole
Case control studies (nested)Case control studies (nested)– Genetic studiesGenetic studies
6666
Don’t ask for too muchDon’t ask for too muchThe more you ask for, the less you getThe more you ask for, the less you get
A delicate balanceA delicate balance
Concomitant therapyConcomitant therapy
Information can be requested if neededInformation can be requested if needed
Unnecessary data increases workloadUnnecessary data increases workload
6767
Be open mindedBe open mindedUnexpected reactions will occurUnexpected reactions will occur
Predictions of safety unreliablePredictions of safety unreliable
Experience based only on spontaneous reporting unreliableExperience based only on spontaneous reporting unreliable– 2.1 million patient exposures with olanzapine 2.1 million patient exposures with olanzapine
’’no significant safety concernsno significant safety concerns’’
No dominant pre-conceived ideasNo dominant pre-conceived ideas
All dataAll data should be collected & analysed in a totally should be collected & analysed in a totally objectiveobjective mannermanner
6868
Cohort event monitoringCohort event monitoringIs an early warning systemIs an early warning system
New drugs (post-marketing surveillance)New drugs (post-marketing surveillance)
Can be used to validate signalsCan be used to validate signals
Can be used to characterize reactionsCan be used to characterize reactions
Normal clinical practice, real life situationsNormal clinical practice, real life situations
6969
Cohort event monitoringCohort event monitoringExposure in pregnancy / lactationExposure in pregnancy / lactationDeath ratesDeath ratesReasons for stopping therapyReasons for stopping therapyInefficacyInefficacyLimited study periodLimited study periodReactions of long latencyReactions of long latencyEvents examined clinically and epidemiologicallyEvents examined clinically and epidemiologically
7070
The epidemiologyThe epidemiologyobservational cohort studiesobservational cohort studiesprospectiveprospectivelongitudinallongitudinalnon-interventionalnon-interventionalinceptionalinceptionaldynamicdynamicdescriptivedescriptive
7171
AnalysisAnalysisCollation and signal identificationCollation and signal identification
Rates and profilesRates and profiles– Comparisons by drug, age group, etcComparisons by drug, age group, etc– By system organ classBy system organ class– Within system organ classWithin system organ class– Individual eventsIndividual events
Life table or survival analysisLife table or survival analysis
Multiple logistic regressionMultiple logistic regression– esp. for risk factorsesp. for risk factors
7272
Advantages of CEMAdvantages of CEMProvides comprehensive informationProvides comprehensive information
Provides near complete informationProvides near complete information– On the target populationOn the target population– Drug utilisationDrug utilisation– EffectivenessEffectiveness– Risks and how to prevent themRisks and how to prevent them
Provides the information needed toProvides the information needed to– Handle drug scaresHandle drug scares– Minimise harmMinimise harm– Ensure treatment successEnsure treatment success
7373
Advantages of CEMAdvantages of CEMStimulates interest in drug safetyStimulates interest in drug safety
Improves spontaneous reportingImproves spontaneous reporting
Can concentrate resources on drugs of particular Can concentrate resources on drugs of particular importance to a country or programmeimportance to a country or programme
Can be applied regionally Can be applied regionally
AdaptableAdaptable
7474
The essentialsThe essentials
Identify the cohortIdentify the cohort
Identify the eventsIdentify the events
With this information, you can find all With this information, you can find all you need to know (almost) you need to know (almost)
concerning safetyconcerning safety
7575
PEM referencesPEM referencesMann & Andrews Mann & Andrews PharmacovigilancePharmacovigilance
Title:Title: Pharmacovigilance (2 Pharmacovigilance (2ndnd Edition) 2007 Edition) 2007Publisher:Publisher: John Wiley & Sons, Ltd. John Wiley & Sons, Ltd.Author:Author: Mann, Ronald D.; Andrews, Elizabeth B. Mann, Ronald D.; Andrews, Elizabeth B.
Includes chapters on:Includes chapters on:PEM in the UKPEM in the UKPEM in NZPEM in NZ
7676
Thank-you
