Kia Ora!

transcript

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)

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

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

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?

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

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

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

9.9. Hypothesis generationHypothesis generation

10.10. Cohorts for studyCohorts for study

The objectivesThe objectives

Achieve Achieve maximum maximum benefitbenefit, , least harmleast harm for for

patientspatients

What results can you get?What results can you get?

COX-2 inhibitorsCOX-2 inhibitorscelecoxib, rofecoxibcelecoxib, rofecoxib

Preliminary monitoring Preliminary monitoring datadata

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

IMMP ProcessIMMP ProcessPrescription

Patient and Prescription details

Follow-up questionnairesEvent information

Cohort data Relationship

assessment

CohortCohort

Prescriptions Patients

Celecoxib 98,975 32,630

Rofecoxib 52,874 26,666

Profile of Ages at First Prescription

213543

5827 5969

503468

4254 4297

< 20 20-30 30-39 40-49 50-59 60-69 70-79 80-89 90 plus

Celecoxib Rofecoxib

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

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%)

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. %

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

assessment

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

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

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%)

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)

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)

The eventsThe events

Profile of Events - Celecoxib and Rofecoxib n=1714 n=982

123532

293301

122121

System Organ Class

Celecoxib Rofecoxib

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

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

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)

Signals identified 1Signals identified 1CoughingCoughingVisual field defect / temp blindnessVisual field defect / temp blindnessAcute psychiatric eventsAcute psychiatric eventsPancreatitisPancreatitisHepatotoxicityHepatotoxicityPsoriasisPsoriasisAcute urinary retentionAcute urinary retention

Signals 2Signals 2Mouth ulcerationMouth ulcerationLower bowel effectsLower bowel effectsCardiac dysrhythmiasCardiac dysrhythmiasCardiac arrestCardiac arrestMyocardial infarction / strokeMyocardial infarction / strokeAnaphylaxisAnaphylaxisSerious skin infectionSerious skin infectionAcute labyrinthitisAcute labyrinthitis

Signals 3Signals 3InteractionsInteractions

Tricyclics causing arrhythmiasTricyclics causing arrhythmiasWarfarin causing increased INR Warfarin causing increased INR (rofecoxib)(rofecoxib)

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)

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

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)

Risk factors 3Risk factors 3Stroke / TIAStroke / TIA– AgeAge– HypertensionHypertension– Inflammatory arthritisInflammatory arthritis

Did we reach the Did we reach the objectives?objectives?

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

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

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

How do we get results like How do we get results like this?this?

The principlesThe principles

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

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)

assessment

Other Rx Sources

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

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

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

Patient and Prescription details Follow-up

questionnairesEvent information

assessment

Other Rx Sources

Other Sources

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

Adverse event (experience)Definition (WHO)

Untoward medical occurrence

temporally associated with the use

of a medicinal product, but not

necessarily causally related

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.

Events = reactions + incidentsEvents = reactions + incidentsReactionsReactions11 DefiniteDefinite22 ProbableProbable33 PossiblePossible

IncidentsIncidents (background noise)(background noise)4 Unlikely4 Unlikely5 Unclassified (conditional) 5 Unclassified (conditional) 6 Unassessable6 Unassessable

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

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.

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

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

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

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

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

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

‘‘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

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

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

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

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

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

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

The epidemiologyThe epidemiologyobservational cohort studiesobservational cohort studiesprospectiveprospectivelongitudinallongitudinalnon-interventionalnon-interventionalinceptionalinceptionaldynamicdynamicdescriptivedescriptive

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

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

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

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

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

Thank-you

Kia Ora!

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