1. PharmacoPharmacoepidemiology??epidemiology??
AvinashAvinash
VigiLant

2. ““A desire to take medicine is, perhaps, the greatA desire to take medicine is, perhaps, the great
feature which distinguishes man from otherfeature which distinguishes man from other
animals”. ---------- Sir William Osler, 1891animals”. ---------- Sir William Osler, 1891

3.  Complex and underperformed task for the manyComplex and underperformed task for the many
PhysicianPhysician
 Skills in making diagnosis and skills inSkills in making diagnosis and skills in
therapeuticstherapeutics
 Rapid Introduction of many modern andRapid Introduction of many modern and
sophisticated new drugs to the marketsophisticated new drugs to the market
VigiLant

4. Risk
Benefit
Ratio
VigiLant

5.  Study of interactions between drugs andStudy of interactions between drugs and
populationpopulation
 Pharmacoepidemiology is thePharmacoepidemiology is the ‘‘study of the use‘‘study of the use
and effects of drugs in large numbers ofand effects of drugs in large numbers of
persons.’’persons.’’
VigiLant

6.  Def:Def: ‘‘Pharmacoepidemiology is the‘‘Pharmacoepidemiology is the
application of epidemiologic reasoning,application of epidemiologic reasoning,
methods, and knowledge to the study of themethods, and knowledge to the study of the
uses and effects (beneficial The and adverse) ofuses and effects (beneficial The and adverse) of
drugs in human populations”.drugs in human populations”.
VigiLant

7. Subdiscipline of Clinical Pharmacology
VigiLant

8.  Involves…Involves…
 Causality and incidence of ADRsCausality and incidence of ADRs
 Effectiveness of new drugs in definesEffectiveness of new drugs in defines
populationspopulations
 Patterns of and variations in prescribing in aPatterns of and variations in prescribing in a
particular health care facility areaparticular health care facility area
 Strategies to improve prescribing and so on….Strategies to improve prescribing and so on….
 Economic impact of drug useEconomic impact of drug use
VigiLant

9. History and evolution ofHistory and evolution of
PharmacoepidemiologyPharmacoepidemiology
 Empiric medicine- Core of many treatmentsEmpiric medicine- Core of many treatments
 Opium and Castor oil have been used sinceOpium and Castor oil have been used since
3500 years ago3500 years ago
 Vaccination in India form 550 BCVaccination in India form 550 BC
 Compliance ofCompliance of materia medicamateria medica of 500 plantsof 500 plants
VigiLant

10.  Isolation of Morphine in 1805Isolation of Morphine in 1805
 History of Drug Regulation in US began in theHistory of Drug Regulation in US began in the
beginning of the 20beginning of the 20thth
CenturyCentury
 1906 in US Pure Food and Drug act was passed1906 in US Pure Food and Drug act was passed
For adulterated and misbranded drugs toFor adulterated and misbranded drugs to
eliminateeliminate
VigiLant

11.  No requirement for proof efficacy and safety ofNo requirement for proof efficacy and safety of
marketed drugmarketed drug
 1937 Sulfanilamide tragedy / 107 died1937 Sulfanilamide tragedy / 107 died
 1938 food and drug cosmetic act was passed, requires1938 food and drug cosmetic act was passed, requires
manufacturer to submit clinical data about drug safetymanufacturer to submit clinical data about drug safety
to the FDA prior to drug marketing, BUT data abt drugto the FDA prior to drug marketing, BUT data abt drug
efficacy was not requiredefficacy was not required
VigiLant

12.  Most significant event in the History of DrugMost significant event in the History of Drug
Regulation “ Thalidomide Disaster”Regulation “ Thalidomide Disaster”
 One country get protected form this disasterOne country get protected form this disaster
 ????? And How????? And How
VigiLant

13. VigiLant

14.  Demonstrate causal relationship of theDemonstrate causal relationship of the in uteroin utero
exposure to thalidomide and rare birth defectexposure to thalidomide and rare birth defect
 Kefuaver- Harris Amendment in 1962Kefuaver- Harris Amendment in 1962: To: To
ensure drug efficacy and drug safety. For theensure drug efficacy and drug safety. For the
first time drug manufacturers are required tofirst time drug manufacturers are required to
prove FDA the effectiveness of their productsprove FDA the effectiveness of their products
before marketing.before marketing.
 Requires more extensive NonclinicalRequires more extensive Nonclinical
Pharmacology and toxicology testing beforePharmacology and toxicology testing before
drug could tested in mandrug could tested in man VigiLant

15.  In addition 3 explicit phases of clinical testingIn addition 3 explicit phases of clinical testing
were requiredwere required
 ““Three phases” of classical trial becomeThree phases” of classical trial become
requirement for drug approval before marketingrequirement for drug approval before marketing
 But information is still lacking at the time whenBut information is still lacking at the time when
drug enters in marketdrug enters in market
VigiLant

16.  In phase III involve relatively small no of patientIn phase III involve relatively small no of patient
but possibly serious AE may not be detectedbut possibly serious AE may not be detected
 No of patient between 1000 to 3000No of patient between 1000 to 3000
 What for rare ADR (1 in 1000)?What for rare ADR (1 in 1000)?
VigiLant

17.  Relatively short period of drug administration inRelatively short period of drug administration in
Phase III clinical trial last NMT 18 monthsPhase III clinical trial last NMT 18 months
which makes longer term effects undetectablewhich makes longer term effects undetectable
 Therefore epidemiological technique have beenTherefore epidemiological technique have been
widely applied to the discipline of clinicalwidely applied to the discipline of clinical
pharmacology known aspharmacology known as PHASE IVPHASE IV Studies orStudies or
PMSPMS
VigiLant

18.  Eg. In 1970 the Bosten University DrugEg. In 1970 the Bosten University Drug
Epidemiology unit was developed, using aEpidemiology unit was developed, using a
hospital – based approach of collecting drughospital – based approach of collecting drug
exposure history to perform hospital based caseexposure history to perform hospital based case
control studiescontrol studies
 1976 joint commission on prescription drug use1976 joint commission on prescription drug use
was performed to review the status of the fieldwas performed to review the status of the field
of Pharmacoepidemiologyof Pharmacoepidemiology
VigiLant

19.  In 1980 DSRU was developed in UK toIn 1980 DSRU was developed in UK to
conduct Prescription Event Monitoring (PEM)conduct Prescription Event Monitoring (PEM)
 All these development are important event inAll these development are important event in
the field of Pharmacoepidemiology in developedthe field of Pharmacoepidemiology in developed
communitiescommunities
VigiLant

20.  Health Expenditure of each nation: 8-10% spentHealth Expenditure of each nation: 8-10% spent
on medications in developed countries but thison medications in developed countries but this
could be more than 35-40 % in many developingcould be more than 35-40 % in many developing
countriescountries
VigiLant

21. Pharmacoepidemiology inPharmacoepidemiology in
Developing CountriesDeveloping Countries
 Poor Regulation of Drug In Developing CountriesPoor Regulation of Drug In Developing Countries
 Many prescription drugs as Antibiotics, Anxiolytics canMany prescription drugs as Antibiotics, Anxiolytics can
be purchased from any drug Store with no controlbe purchased from any drug Store with no control
 Self Medication and Local Remedies ??Self Medication and Local Remedies ??
 WHO, FDA, TGA, International Network of ClinicalWHO, FDA, TGA, International Network of Clinical
EpidemiologyEpidemiology

22. Study Design inStudy Design in
PharmacoepidemiologyPharmacoepidemiology
 Randomized Clinical Trial (RCT) [ ExperimentalRandomized Clinical Trial (RCT) [ Experimental
Study]Study]
 Case Control StudyCase Control Study
 Case ReportCase Report
 Analysis of Secular trends case seriesAnalysis of Secular trends case series
VigiLant

23. Case ReportCase Report
 Prior to testing any hypothesis the hypothesisPrior to testing any hypothesis the hypothesis
must be generatedmust be generated
 How??How??
 By collecting case reportBy collecting case report
 Most simple form of theMost simple form of the
Pharmacoepidemiological StudyPharmacoepidemiological Study
VigiLant

24.  Report of single patientReport of single patient
 Describe a single patient who was exposed to aDescribe a single patient who was exposed to a
drug and experienced a particular adversedrug and experienced a particular adverse
outcomeoutcome
 Eg. Published case Report about young patientEg. Published case Report about young patient
who was taking an antihistamine and developedwho was taking an antihistamine and developed
a serious cardiac arrhythmiaa serious cardiac arrhythmia
VigiLant

25. Case SeriesCase Series
 Collection of the patient with single exposure,Collection of the patient with single exposure,
whose clinical outcome are evaluated andwhose clinical outcome are evaluated and
describeddescribed
 Useful after drug marketing for an easyUseful after drug marketing for an easy
quantification of the incidence of an ADRquantification of the incidence of an ADR
 Eg. Post marketing studies of the “First- DoseEg. Post marketing studies of the “First- Dose
Effect” of Prazosin when drug was firstEffect” of Prazosin when drug was first
marketedmarketed
VigiLant

26. Case- Control StudyCase- Control Study
 Compares cases with a disease to controlsCompares cases with a disease to controls
without diseasewithout disease
 Eg. GI Bleeding form NSAID including cases ofEg. GI Bleeding form NSAID including cases of
patient with GI bleeding and compare them topatient with GI bleeding and compare them to
control without diseasecontrol without disease
 Difference in prior to exposure to NSAIDs andDifference in prior to exposure to NSAIDs and
GI BleedingGI Bleeding
VigiLant

27. Case-Cohort StudyCase-Cohort Study
 Identifies an exposed group and follows themIdentifies an exposed group and follows them
over the timeover the time
 Look for the differences in their outcomeLook for the differences in their outcome
 Comparison between exposed patient toComparison between exposed patient to
unexposed patientunexposed patient
VigiLant

28. Approach in EpidemiologicalApproach in Epidemiological
StudiesStudies
 General Data:General Data:
 By Asking QuestionsBy Asking Questions
 By Making ComparisonBy Making Comparison
 ActionsActions
How to solve this problemHow to solve this problem
How it can prevented in futureHow it can prevented in future
What is the role of community, society, and healthWhat is the role of community, society, and health
CareCare
VigiLant

29.  Incidence: “ The Number of new cases occurredIncidence: “ The Number of new cases occurred
in define population during a specified period ofin define population during a specified period of
time”time”
 Prevalence: All current and existing cases at aPrevalence: All current and existing cases at a
given time over a period in a population”given time over a period in a population”
VigiLant

30. Potential AreasPotential Areas
 Potential Areas of PharmacoepidemiologicalPotential Areas of Pharmacoepidemiological
Study includeStudy include
 Identifying and QuantifyingIdentifying and Quantifying
 Less common adverse eventsLess common adverse events
 Delayed Adverse eventsDelayed Adverse events
 Evaluation of safety/efficacy/toxicity in specificEvaluation of safety/efficacy/toxicity in specific
patient group in phase IVpatient group in phase IV
 Study on Unanticipated AEStudy on Unanticipated AE VigiLant

31. ApplicationApplication
 Use of DrugUse of Drug
 Drug EfficacyDrug Efficacy
 SafetySafety
 Cost-effectivenessCost-effectiveness
 Drug UtilizationDrug Utilization
VigiLant

32. Drug UtilizationDrug Utilization
VigiLant

33. STUDY RATIONALESTUDY RATIONALE
 To develop a National drug policy and Rational drug use, it isTo develop a National drug policy and Rational drug use, it is
necessary to determine drug use patterns and monitor drug usenecessary to determine drug use patterns and monitor drug use
profiles over timeprofiles over time
 A first step is to describe the utilization in a Quantitative wayA first step is to describe the utilization in a Quantitative way
using the anatomical-chemical therapeutic code/daily definedusing the anatomical-chemical therapeutic code/daily defined
dose (ATC/DDD) methodologydose (ATC/DDD) methodology
 To describe the utilization in a Qualitative way using DU 90To describe the utilization in a Qualitative way using DU 90
methodologymethodology
VigiLant

34. STUDY OBJECTIVESSTUDY OBJECTIVES
 To evaluate drug utilization in orthopedic population atTo evaluate drug utilization in orthopedic population at
civil hospital Nashik with special reference to NSAIDscivil hospital Nashik with special reference to NSAIDs
 To monitor prescribing practices at civil hospitalTo monitor prescribing practices at civil hospital
Nashik with aim of making medical care rational & costNashik with aim of making medical care rational & cost
effectiveeffective
VigiLant

35. MATERIALS & METHODSMATERIALS & METHODS
 A prospective cross-sectional study was undertaken ,A prospective cross-sectional study was undertaken ,
prescriptions of the patients who were examined by physician inprescriptions of the patients who were examined by physician in
OPD &IPD were collected & copied and the patients wereOPD &IPD were collected & copied and the patients were
interviewed.interviewed.
 Analysis was done as per WHO indicators & DDD wasAnalysis was done as per WHO indicators & DDD was
calculated, and DU 90% was obtainedcalculated, and DU 90% was obtained
*ATC index with DDDs. Oslo, Norway,WHO Collaborating *ATC index with DDDs. Oslo, Norway,WHO Collaborating
Centre for Drug Statistics Methodology,2003.Centre for Drug Statistics Methodology,2003.
VigiLant

36. FOR EG: UTILIZATION OF NSAIDSFOR EG: UTILIZATION OF NSAIDS
DRUGS IN RIKEKA & STOCKHOLMDRUGS IN RIKEKA & STOCKHOLM

37.  STUDY DESIGN:STUDY DESIGN: Prospective Cross-sectional StudyProspective Cross-sectional Study
 Number of sites:Number of sites: oneone
 Number of subjects:Number of subjects: Total of 140 PatientsTotal of 140 Patients
 Subject type:Subject type: All age groups of either sexAll age groups of either sex
 Study duration:Study duration: 2 weeks2 weeks
 INCLUSION CRITERIA: Patients who are ready to give informationINCLUSION CRITERIA: Patients who are ready to give information
After obtaining ,oral consent, patients fulfilling inclusion and exclusion criteria
were included in the study.
VigiLant

38. FLOW CHART OF THE STUDY
PRESCRIPTION STUDY OF THE PATIENT
IDENTIFICATION OF THE PATIENT
INTERVIEW OF THE PATIENT
DATA COLLECTION & ANALYSIS
REPORT
VigiLant

39. CORE INDICATORSCORE INDICATORS
 Prescribing indicatorsPrescribing indicators
 Average number of drugs per encounterAverage number of drugs per encounter
 Percentage of drugs prescribed by generic name Percentage of drugs prescribed by generic name
 Percentage of encounters with an injection prescribed Percentage of encounters with an injection prescribed
 Percentage of drugs prescribed from essential drug listPercentage of drugs prescribed from essential drug list
VigiLant

40. CORE INDICATORSCORE INDICATORS
 Patient Care IndicatorsPatient Care Indicators
 Average consultation timeAverage consultation time
 Average dispensing timeAverage dispensing time
 Percentage of drugs actually dispensedPercentage of drugs actually dispensed
 Patients' knowledge of correct dosagePatients' knowledge of correct dosage
 Complementary indicatorsComplementary indicators
 Percentage of patients treated without drugsPercentage of patients treated without drugs
 Average drug cost per encounterAverage drug cost per encounter
VigiLant

41. THE CONCEPT OF THE DEFINED DAILY DOSE
(DDD)
 The DDD is the assumed average maintenance dose per day for a
drug used for its main indication in adults.
 Drug Classification Systems represents a common language
for describing the drug assortment in a country or region. In 1996,
WHO established the ATC/DDD system as an international standard
in drug utilization studies.
 The ATC classification system : the drugs are divided into
different groups according to the organ or system on which they act
and their chemical, pharmacological and therapeutic properties.
VigiLant

42. DDD/1000/DayDDD/1000/Day
 It is derived by calculating the overall amount of drug being used overIt is derived by calculating the overall amount of drug being used over
a specific period of time and dividing this by DDDa specific period of time and dividing this by DDD (ATC)(ATC) multipliedmultiplied
by the population and the number of days in the periodby the population and the number of days in the period
 DDD/1000/DAYDDD/1000/DAY ==
Total no of dosage units prescribed * Strength of each dose unit * 1000Total no of dosage units prescribed * Strength of each dose unit * 1000
DDD(ATC) * Duration of the study * Total sample sizeDDD(ATC) * Duration of the study * Total sample size
*ATC index with DDDs. Oslo, Norway,WHO Collaborating Centre for Drug*ATC index with DDDs. Oslo, Norway,WHO Collaborating Centre for Drug
Statistics Methodology,2003.Statistics Methodology,2003.
VigiLant

43. DU 90% FOR EG:DU 90% FOR EG:

44. RESULTSRESULTS
 Total no.of patients studied = 140 OPD+IPD (118+22)Total no.of patients studied = 140 OPD+IPD (118+22)
 Total no.of prescriptions = 140Total no.of prescriptions = 140
 Total no. of drugs dispensed = 489Total no. of drugs dispensed = 489
VigiLant

45. PRESCRIPTION INDICATORSPRESCRIPTION INDICATORS
Avg. number of drugs/prescription 489/140 3.49 = 3
Drugs in injectable form 86/489 X
100
17.59%
Drugs prescribed by generic name 180/489 X
100
36.81%
Drugs from essential drug list 99%
VigiLant

46. PATIENT CARE INDICATORS PATIENT CARE INDICATORS
Avg. consultation timeAvg. consultation time 5 min IPD5 min IPD
2 min OPD2 min OPD
Avg. dispensing timeAvg. dispensing time 1 min1 min
Number of drugs actuallyNumber of drugs actually
dispenseddispensed
470 = 96.11%470 = 96.11%
Number of drugs actuallyNumber of drugs actually
labeledlabeled
100%100%
Patient’s knowledge aboutPatient’s knowledge about
correct dosecorrect dose
97 were aware =69.29%97 were aware =69.29%
43 were unaware=30.71%43 were unaware=30.71%
VigiLant

47. PERCENTAGE OF NSAIDSPERCENTAGE OF NSAIDS
PRESCRIBEDPRESCRIBED
0
10
20
30
40
50
60
70
80
90
100
ORAL I V I PD OPD
NSAI DS
VigiLant

48. DDD IN PERCENTAGEDDD IN PERCENTAGE
DDD in Percentage
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
Brufen Voveran
DDD in
Percentage
VigiLant

49. DrugDrug (IV)(IV) PercentagePercentage
Inj VoveranInj Voveran 15.7115.71
Inj AmikacinInj Amikacin 7.867.86
Inj RantacInj Rantac 9.299.29
Inj. T.T.Inj. T.T. 55
Inj TaximInj Taxim 10.7910.79
Inj GentaInj Genta 2.862.86
Inj DexaInj Dexa 2.862.86
Drug(Oral)Drug(Oral) PercentagePercentage
Tab. BrufenTab. Brufen 55.8655.86
Tab. VoveranTab. Voveran 29.2929.29
Tab. RantacTab. Rantac 71.4371.43
Tab.M.V.B.CTab.M.V.B.C 39.2939.29
Tab.Cal.lactateTab.Cal.lactate 33.533.5
Tab.SeptranTab.Septran 3.53.5
Tab.CetrizineTab.Cetrizine 1.431.43
PERCENTAGE OF DRUGS DISPENSEDPERCENTAGE OF DRUGS DISPENSED

50. COST ANALYSIS
Average cost per prescription in IPD = 19142/22 = Rs 870.90
Average cost per prescription in OPD = Rs 38.36
Average cost of tablets per prescription in OPD = Rs 31.81
Average cost of tablets per prescription in IPD = Rs 37.00
Average cost of injectables prescribed in OPD = Rs 4.55
Average cost of injectables prescribed in IPD = Rs 833.90

51. LIMITATIONS OF THE STUDYLIMITATIONS OF THE STUDY
 Study durationStudy duration
 Number of prescriptions analyzedNumber of prescriptions analyzed
 Choice of NSAID available for prescriptionChoice of NSAID available for prescription
 Socio-economic class group representationSocio-economic class group representation
inadequateinadequate VigiLant

52. ThankThank
You…You…
VigiLant