PharmacoPharmacoepidemiolepidemiology??ogy??

AvinashAvinash

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

Complex and underperformed task Complex and underperformed task for the many Physician for the many Physician

Skills in making diagnosis and skills Skills in making diagnosis and skills in therapeutics in therapeutics

Rapid Introduction of many modern Rapid Introduction of many modern and sophisticated new drugs to the and sophisticated new drugs to the market market

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RiskBenefit

Ratio

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Study of interactions between drugs Study of interactions between drugs and populationand population

Pharmacoepidemiology is the Pharmacoepidemiology is the ‘‘study ‘‘study of the use and effects of drugs in of the use and effects of drugs in large numbers of persons.’’large numbers of persons.’’

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

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Subdiscipline of Clinical Pharmacology

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Involves…Involves… Causality and incidence of ADRsCausality and incidence of ADRs Effectiveness of new drugs in defines Effectiveness of new drugs in defines

populations populations Patterns of and variations in prescribing Patterns of and variations in prescribing

in a particular health care facility area in a particular health care facility area Strategies to improve prescribing and so Strategies to improve prescribing and so

on….on…. Economic impact of drug useEconomic impact of drug use

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History and evolution of History and evolution of Pharmacoepidemiology Pharmacoepidemiology

Empiric medicine- Core of many Empiric medicine- Core of many treatments treatments

Opium and Castor oil have been used Opium and Castor oil have been used since 3500 years agosince 3500 years ago

Vaccination in India form 550 BCVaccination in India form 550 BC

Compliance of Compliance of materia medicamateria medica of 500 of 500 plants plants

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Isolation of Morphine in 1805Isolation of Morphine in 1805

History of Drug Regulation in US began History of Drug Regulation in US began in the beginning of the 20in the beginning of the 20thth Century Century

1906 in US Pure Food and Drug act was 1906 in US Pure Food and Drug act was passed passed

For adulterated and misbranded drugs For adulterated and misbranded drugs to eliminate to eliminate

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No requirement for proof efficacy and No requirement for proof efficacy and safety of marketed drugsafety of marketed drug

1937 Sulfanilamide tragedy / 107 died 1937 Sulfanilamide tragedy / 107 died

1938 food and drug cosmetic act was 1938 food and drug cosmetic act was passed, requires manufacturer to submit passed, requires manufacturer to submit clinical data about drug safety to the FDA clinical data about drug safety to the FDA prior to drug marketing, BUT data abt prior to drug marketing, BUT data abt drug efficacy was not required drug efficacy was not required

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Most significant event in the History Most significant event in the History of Drug Regulation “ Thalidomide of Drug Regulation “ Thalidomide Disaster” Disaster”

One country get protected form this One country get protected form this disaster disaster

????? And How ????? And How VigiLant

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Demonstrate causal relationship of the Demonstrate causal relationship of the in in uteroutero exposure to thalidomide and rare birth exposure to thalidomide and rare birth defect defect

Kefuaver- Harris Amendment in 1962Kefuaver- Harris Amendment in 1962: To : To ensure drug efficacy and drug safety. For the ensure drug efficacy and drug safety. For the first time drug manufacturers are required to first time drug manufacturers are required to prove FDA the effectiveness of their products prove FDA the effectiveness of their products before marketing. before marketing.

Requires more extensive Nonclinical Requires more extensive Nonclinical Pharmacology and toxicology testing before Pharmacology and toxicology testing before drug could tested in man drug could tested in man

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In addition 3 explicit phases of clinical In addition 3 explicit phases of clinical testing were required testing were required

““Three phases” of classical trial Three phases” of classical trial become requirement for drug become requirement for drug approval before marketing approval before marketing

But information is still lacking at the But information is still lacking at the time when drug enters in market time when drug enters in market

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In phase III involve relatively small In phase III involve relatively small no of patient but possibly serious no of patient but possibly serious AE may not be detected AE may not be detected

No of patient between 1000 to 3000 No of patient between 1000 to 3000

What for rare ADR (1 in 1000)?What for rare ADR (1 in 1000)?

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Relatively short period of drug Relatively short period of drug administration in Phase III clinical administration in Phase III clinical trial last NMT 18 months which makes trial last NMT 18 months which makes longer term effects undetectablelonger term effects undetectable

Therefore epidemiological technique Therefore epidemiological technique have been widely applied to the have been widely applied to the discipline of clinical pharmacology discipline of clinical pharmacology known as known as PHASE IVPHASE IV Studies or Studies or PMS PMS

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Eg. In 1970 the Bosten University Drug Eg. In 1970 the Bosten University Drug Epidemiology unit was developed, using Epidemiology unit was developed, using a hospital – based approach of collecting a hospital – based approach of collecting drug exposure history to perform drug exposure history to perform hospital based case control studieshospital based case control studies

1976 joint commission on prescription 1976 joint commission on prescription drug use was performed to review the drug use was performed to review the status of the field of status of the field of Pharmacoepidemiology Pharmacoepidemiology

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In 1980 DSRU was developed in UK In 1980 DSRU was developed in UK to conduct Prescription Event to conduct Prescription Event Monitoring (PEM) Monitoring (PEM)

All these development are important All these development are important event in the field of event in the field of Pharmacoepidemiology in developed Pharmacoepidemiology in developed communities communities

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Health Expenditure of each nation: Health Expenditure of each nation: 8-10% spent on medications in 8-10% spent on medications in developed countries but this could developed countries but this could be more than 35-40 % in many be more than 35-40 % in many developing countries developing countries

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Pharmacoepidemiology in Pharmacoepidemiology in Developing Countries Developing Countries

Poor Regulation of Drug In Developing Poor Regulation of Drug In Developing Countries Countries

Many prescription drugs as Antibiotics, Many prescription drugs as Antibiotics, Anxiolytics can be purchased from any drug Anxiolytics can be purchased from any drug Store with no control Store with no control

Self Medication and Local Remedies ?? Self Medication and Local Remedies ??

WHO, FDA, TGA, International Network of WHO, FDA, TGA, International Network of Clinical Epidemiology Clinical Epidemiology

Study Design in Study Design in Pharmacoepidemiology Pharmacoepidemiology

Randomized Clinical Trial (RCT) Randomized Clinical Trial (RCT) [ Experimental Study] [ Experimental Study]

Case Control StudyCase Control Study Case Report Case Report Analysis of Secular trends case Analysis of Secular trends case

series series

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Case Report Case Report

Prior to testing any hypothesis the Prior to testing any hypothesis the hypothesis must be generated hypothesis must be generated

How??How??

By collecting case report By collecting case report

Most simple form of the Most simple form of the Pharmacoepidemiological Study Pharmacoepidemiological Study

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Report of single patient Report of single patient

Describe a single patient who was Describe a single patient who was exposed to a drug and experienced a exposed to a drug and experienced a particular adverse outcome particular adverse outcome

Eg. Published case Report about Eg. Published case Report about young patient who was taking an young patient who was taking an antihistamine and developed a serious antihistamine and developed a serious cardiac arrhythmia cardiac arrhythmia

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Case Series Case Series

Collection of the patient with single Collection of the patient with single exposure, whose clinical outcome are exposure, whose clinical outcome are evaluated and described evaluated and described

Useful after drug marketing for an Useful after drug marketing for an easy quantification of the incidence of easy quantification of the incidence of an ADRan ADR

Eg. Post marketing studies of the Eg. Post marketing studies of the “First- Dose Effect” of Prazosin when “First- Dose Effect” of Prazosin when drug was first marketed drug was first marketed

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Case- Control Study Case- Control Study

Compares cases with a disease to Compares cases with a disease to controls without disease controls without disease

Eg. GI Bleeding form NSAID Eg. GI Bleeding form NSAID including cases of patient with GI including cases of patient with GI bleeding and compare them to bleeding and compare them to control without disease control without disease

Difference in prior to exposure to Difference in prior to exposure to NSAIDs and GI Bleeding NSAIDs and GI Bleeding

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Case-Cohort Study Case-Cohort Study

Identifies an exposed group and Identifies an exposed group and follows them over the timefollows them over the time

Look for the differences in their Look for the differences in their outcome outcome

Comparison between exposed Comparison between exposed patient to unexposed patient patient to unexposed patient

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Approach in Approach in Epidemiological Studies Epidemiological Studies

General Data:General Data: By Asking QuestionsBy Asking Questions By Making ComparisonBy Making Comparison

Actions Actions

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, What is the role of community, society, and health and health CareCare

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Incidence: “ The Number of new Incidence: “ The Number of new cases occurred in define population cases occurred in define population during a specified period of time”during a specified period of time”

Prevalence: All current and existing Prevalence: All current and existing cases at a given time over a period cases at a given time over a period in a population” in a population”

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Potential AreasPotential Areas

Potential Areas of Potential Areas of Pharmacoepidemiological Study includePharmacoepidemiological Study include

Identifying and Quantifying Identifying and Quantifying Less common adverse eventsLess common adverse events Delayed Adverse eventsDelayed Adverse events

Evaluation of safety/efficacy/toxicity in Evaluation of safety/efficacy/toxicity in specific patient group in phase IVspecific patient group in phase IV

Study on Unanticipated AEStudy on Unanticipated AEVigiLant

Application Application

Use of DrugUse of Drug Drug Efficacy Drug Efficacy SafetySafety Cost-effectivenessCost-effectiveness Drug Utilization Drug Utilization

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Drug UtilizationDrug Utilization

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STUDY RATIONALESTUDY RATIONALE To develop a National drug policy and Rational To develop a National drug policy and Rational

drug use, it is necessary to determine drug use drug use, it is necessary to determine drug use patterns and monitor drug use profiles over time patterns and monitor drug use profiles over time

A first step is to describe the utilization in a A first step is to describe the utilization in a Quantitative way using the anatomical-chemical Quantitative way using the anatomical-chemical therapeutic code/daily defined dose (ATC/DDD) therapeutic code/daily defined dose (ATC/DDD) methodology methodology

To describe the utilization in a Qualitative way To describe the utilization in a Qualitative way using DU 90 methodologyusing DU 90 methodology

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STUDY OBJECTIVESSTUDY OBJECTIVES To evaluate drug utilization in orthopedic To evaluate drug utilization in orthopedic

population at civil hospital Nashik with population at civil hospital Nashik with special reference to NSAIDsspecial reference to NSAIDs

To monitor prescribing practices at civil To monitor prescribing practices at civil hospital Nashik with aim of making hospital Nashik with aim of making medical care rational & cost effectivemedical care rational & cost effective

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MATERIALS & METHODSMATERIALS & METHODS

A prospective cross-sectional study was A prospective cross-sectional study was undertaken , prescriptions of the patients who undertaken , prescriptions of the patients who were examined by physician in OPD &IPD were were examined by physician in OPD &IPD were collected & copied and the patients were collected & copied and the patients were interviewed. interviewed.

Analysis was done as per WHO indicators & DDD Analysis was done as per WHO indicators & DDD was calculated, and DU 90% was obtainedwas calculated, 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.

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FOR EG: UTILIZATION OF FOR EG: UTILIZATION OF NSAIDS DRUGS IN RIKEKA & NSAIDS DRUGS IN RIKEKA &

STOCKHOLM STOCKHOLM

STUDY DESIGN: STUDY DESIGN: Prospective Cross-sectional StudyProspective Cross-sectional Study

Number of sites:Number of sites: one one

Number of subjects:Number of subjects: Total of 140 Patients Total of 140 Patients

Subject type:Subject type: All age groups of either sex All age groups of either sex

Study duration:Study duration: 2 weeks 2 weeks

INCLUSION CRITERIA: Patients who are ready to give INCLUSION CRITERIA: Patients who are ready to give informationinformation

After obtaining ,oral consent, patients fulfilling inclusion and exclusion criteria were included in the study.

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FLOW CHART OF THE STUDY

PRESCRIPTION STUDY OF THE PATIENT

IDENTIFICATION OF THE PATIENT

INTERVIEW OF THE PATIENT

DATA COLLECTION & ANALYSIS

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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

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CORE INDICATORSCORE INDICATORS

Patient Care IndicatorsPatient Care Indicators

Average consultation time Average consultation time Average dispensing time Average dispensing time Percentage of drugs actually dispensed Percentage of drugs actually dispensed Patients' knowledge of correct dosage Patients' knowledge of correct dosage

Complementary indicatorsComplementary indicators

Percentage of patients treated without drugs Percentage of patients treated without drugs Average drug cost per encounter Average drug cost per encounter

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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.

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DDD/1000/DayDDD/1000/Day

It is derived by calculating the overall amount of drug being It is derived by calculating the overall amount of drug being used over a specific period of time and dividing this by DDD used over a specific period of time and dividing this by DDD (ATC)(ATC) multiplied by the population and the number of days in multiplied by the population and the number of days in the periodthe 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 Statistics *ATC index with DDDs. Oslo, Norway,WHO Collaborating Centre for Drug Statistics Methodology,2003.Methodology,2003.

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DU 90% FOR EG:DU 90% FOR EG:

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

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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%

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PATIENT CARE INDICATORS PATIENT CARE INDICATORS 

Avg. consultation Avg. consultation timetime

5 min IPD5 min IPD

2 min OPD2 min OPD

Avg. dispensing timeAvg. dispensing time 1 min1 min

Number of drugs Number of drugs actually dispensedactually dispensed

470 = 96.11%470 = 96.11%

Number of drugs Number of drugs actually labeledactually labeled

100%100%

Patient’s knowledge Patient’s knowledge about correct doseabout correct dose

97 were aware 97 were aware =69.29%=69.29%

43 were 43 were unaware=30.71%unaware=30.71%

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PERCENTAGE OF NSAIDS PERCENTAGE OF NSAIDS PRESCRIBEDPRESCRIBED

0102030405060708090

100

ORAL IV IPD OPD

NSAIDS

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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 inPercentage

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DrugDrug (IV) (IV) PercentagePercentage

Inj Inj VoveranVoveran

15.7115.71

Inj Inj AmikacinAmikacin

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) PercentagPercentagee

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.lactaTab.Cal.lactatete

33.533.5

Tab.SeptranTab.Septran 3.53.5

Tab.CetrizineTab.Cetrizine 1.431.43

PERCENTAGE OF DRUGS PERCENTAGE OF DRUGS DISPENSEDDISPENSED

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 31.81Average 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

LIMITATIONS OF THE STUDYLIMITATIONS OF THE STUDY

Study durationStudy duration

Number of prescriptions analyzedNumber of prescriptions analyzed

Choice of NSAID available for Choice of NSAID available for prescriptionprescription

Socio-economic class group Socio-economic class group representation inadequaterepresentation inadequate

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Thank Thank You…You…

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