Rational Drug Use

CHAPTER # 01

RATIONAL USE OF DRUGS

Contents … Rational use of drugs

Approaches to rationale use of drugs

Rationale prescribing

Irrational use of drugs

Factors responsible for irrational use of drugs

How to avoid irrational use of drugs

Sampling of drug use

Study design

Sampling methods

Iftikhar Ahmad

Session: 09-14

Cha # 1 Rationale Use of Drugs

Page |2CHAPTER # 01 RATIONAL USE OF DRUGS

Rational use of drugs:

According to W.H.O , rational use of drugs requires that patient receives medication, appropriateto their clinical needs, in the doses that meet their own individual requirements, for adequateperiod of time and to the lowest cost of them and their community.

Approaches to achieve rational use of drugs:

Rational use of drugs can be achieved by going through following steps.

i. Patient problem.ii. Diagnosis

iii. Therapeutic goalsiv. Select the treatmentv. Start the medication

vi. Result of therapyvii. Conclusion of therapy

i. Patient problem:The clinician should try to find explanation to the patient problem. Two factors mayprove helpful in this case:- History of illness.- Patient history of medication.

ii. Diagnosis:It can be made by:- Past medical history- Past medication history- Present complaints

An accurate diagnosis is pre-requisite for rational use of drug. If patient is not diagnosedproperly, the use of drugs becomes irrational.

iii. Therapeutic goals:Primarily, the therapeutic goals should include;- Relieving of symptoms- Prevention of disease- Combination of both


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iv. Select the treatment:Selection of treatment has two phases:

Phase-I:In phase-I, it is determined that either any simple option is available i.e there is no needof the drug. Anyhow, if drug use is necessary, suitable group of drug is selected.

Phase-II :In this phase, the drug is evaluated on the basis of:- Efficacy- Safety- Ease of administration- Easy availability- Cost effectiveness- Storage condition

v. Start the treatment: Inform the patient about the beneficial and side effects of the drug.

Instruct the patient how to deal with the side effects. Patient should be given a date for the next visit so that result can be concluded.

vi. Result of therapy:It should be assessed that if the problem has solved, therapy is rational and if, responsehas not been shown, the therapy is irrational.

vii. Conclusion:Determine; If therapeutic objective has been achieved or not. Has the drug use solved the patient problem?

RATIONAL PRESCRIBING

Definition

The right dose of the right drug for the right diagnosis to the right patient at right time and viaright route is called rational prescribing.

It is a balancing act that is composed of four major components.

i. Maximizing effectiveness.ii. Minimizing risks.

iii. Minimizing costs.


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iv. Respecting the patient choice.

Criteria for Rational Prescribing

i. Appropriate diagnosisii. Appropriate medication

iii. Appropriate patientiv. Appropriate dose and dosage regimenv. Appropriate route of administration

vi. Appropriate durationvii. Appropriate information

viii. Appropriate monitoring plantix. Appropriate program for patient education

i. Appropriate diagnosisAppropriate diagnosis is based upon clinical picture and laboratory tests. Clinical pictureplays important role when lab facilities are not available, especially in remote areas.For example, pneumonia in children can be diagnosed by counting the respiratory rateand dwelling of chest in the absence of lab facilities.Similarly a 35 years old woman suffering from pain in joints, stiffness, inflammation,worsening early in the morning should be considered as patient of rheumatoid arthritis.The diagnosis should be shared with the patient. It will save time, money and labor work.

Pathophysiological implications of diagnosis:If pathophysiology of the patient is well understood, the prescriber is in a better positionto prescribe more rationally. E.g in rheumatoid arthritis, there is increase level ofinflammatory mediators. So the sound knowledge of all these mediators is very necessaryfor prescriber in order to make proper diagnosis and rational prescription.

Selection of therapeutic objectives:

Therapeutic objectives are of two types:(1). Short term therapeutic objectives(2). Long term therapeutic objectives

Short term therapeutic goals include:- Relief of pain- Reduction of inflammation by decreasing level of mediators.

Long term therapeutic goals include:

- Prevention of disease


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- Prevent recurrences- Prevent complications

ii. Appropriate medications:The prescriber should know that either drug is needed or not.The decision to prescribe medication depends upon medical rational. For example,Diarrhea, may be viral (due to Rota virus) which needs no treatment or bacterial whichrequires appropriate medication

Selection of drug of choice:It is based upon following criteria:

- Efficacy,- Suitability,- Cost consideration- Easy availability.

For selection of drug of choice, make list of all available options and then select thegroup on the basis of above mentioned criteria.

The selection of group of choice is based upon host factors such as age, other diseases orother therapy the patient is already taking.Examples:

Penicillin sensitive patient should be given other antibiotics. Aspirin is contraindicated for less than 12 years of age. Ciprofloxacin is contraindicated in pregnancy and children.

iii. Appropriate patientIt should be ensured that:

- No contraindication exists.- Likelihood of ADRs is minimal.

It is better to avoid drug during pregnancy and lactation.

Drug use in pregnancy is done by weighing the risk-benefit ratio of mother or fetus.

iv. Appropriate dose and dosage regimenAppropriate dose should be prescribed for all categories of patients. It is necessarybecause the dosage adjustment is required for pediatric and geriatric patients due to theirlow metabolizing capacity of vital organs.


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Dosage regimen is determined by the pharmacokinetic of drug but patient history andconcomitted diseases such as renal and hepatic insufficiency should also be consideredbefore prescription.Similarly for drugs accumulated in the kidney and metabolized in the liver, dose is alsoadjusted e.g. penicillin.

v. Appropriate route of administrationIf oral route is possible, avoid parentral route because parentral route is;

- Expensive- Increased risk of ADRs chances- Against rational criteria

vi. Appropriate durationIn certain disease, the prescriber fix the duration. But in some cases duration is not fixedsuch as severe illness and chronic diseases.For example, in case of cholera tetracyclies should be used for 3-days only. If it is usedfor 5-7 days, it is irrational.

vii. Appropriate informationPatient should be provided with relevant, accurate and clear information about his/herown condition and medication.

viii. Appropriate monitoring planMonitoring plan is of two types:

a. Active monitoring plan:It is done by the physician with the help of lab investigation and physicalexamination.

b. Passive monitoring plan;It is done by the patient him/herself by telling the symptoms.

Advantage: it tells the patient not to stop medication before specified time.

On this basis disease can be categorized into two categories.

Disease that need little and limited therapy:In this patient should be told not to stop the medication before the therapy course is over.

Disease that need prolong and indefinite therapy:In this the patient should be told that if he/she feels any other symptoms or ADRs, he/sheshould contact the prescriber.e.g rheumatoid arthritis.


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ix. Appropriate program for patient educationThe physician and other health care members should be prepared to repeat, extend andreinforce patient education program to make the drug use more rational.Greater the potency of a drug, greater would be the need for patient education.

Irrational drug use

The ultimate medical criteria for drug use is to prevent, cure or relieve the diseases on the basisof scientific documentation but unfortunately in real world prescribing pattern does not alwaysconfer to these standards and as a result there is irrational drug use.

Key points responsible for irrational drug use

i. Selection of Drugii. Patient characteristics

iii. Lack of patient education and complianceiv. Incorrect prescribingv. Inappropriate prescribing

vi. Overprescribingvii. Multiple prescribing

viii. Inappropriate administrationix. Use of expensive drugs

i. Selection of drugFind whether the drug is selected on the basis of efficacy, safety, cost and availability.e.g.Use of antimotility agents in acute diarrhea have doubtful and unproven efficacy. Forsuch case attapulgite is the ist drug of choice.

ii. Patient characteristicsPresence of factors such as hepatic or renal impairment may need:

Change in drug. Change in dosage and duration.

Change in dosage form.For Example;Metronidazole normal dose is 900-1200 mg/day.In case of hepatic insufficiency, the dose is to be reduced up to 300 mg/day.

iii. Lack of Patient education and compliancePatient should be informed about the drug effects, side effects, warning and precautions.Lack of these information, result in patient non-compliance leading to the irrational druguse.


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iv. Incorrect PrescribingIt occurs when proper diagnosis has not been made, so the drugs prescribed will not bethe true drugs i.e wrong drug is prescribed due to wrong diagnosis or lack of knowledge.Wrong diagnosis example: Use of tetracycline in childhood diarrhea when they can betreated with O.R.S.Lack of knowledge example: Substitution of ciprofloxacin with erythromycin.(Note: Always start with narrow spectrum antibiotics)

v. Inappropriate prescribing:In certain cases, the drug prescribed is not the drug of choice.e.g in endocarditisaminoglycoside and penicillin groups are drugs of choice. If ceftriaxone is prescribed, itis irrational. Similarly prescription of antibiotics for viral respiratory infection would beirrational.

vi. OverprescribingIt includes;

a. Polypharmacy.b. Combination of two or more drugs.c. When the drug in the prescription is not needed.d. Excessive dose.e. Unnecessary long time treatment.

vii. Multiple prescribingIt means prescription contains large number of drugs although few drugs can producebeneficial effects.

viii. Inappropriate administrationIt means the selection of parentral route when the oral route is feasible and vice versa.E.g selection of Ampicillin-G injection is inappropriate administration for a stablepatient, so select ampicillin capsules.

ix. Use of expensive drugsUse of expensive drugs is irrational such as prescription of 3rd generation cephalosporinsis irrational when the spectrum is covered by ist and 2nd generation cephalosporins.The use of expensive medicines in Pakistan is due to promotional activities ofpharmaceutical firms.


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Factors Responsible For Irrational Drug Use

Following factors may be considered responsible for irrational drug use.i. Patient related factors.ii. Prescriber related factors.iii. Work-place related factors.iv. Drug related factors.

i. Patient related FactorsThese include:a. Drug informationb. Misleading believing about therapyc. Patient demand and expectationd. OTCe. Self treatmentf. Taking drugs more than instructed.g. Selecting inappropriate route of administration

ii. Prescriber related FactorsThese include:

a. Lack of education and training.b. Misleading belief about drug efficacy.c. Lack of objective drug information.

iii. Work place related factorsThese include:

a. Heavy patient load.b. Lack of lab facilities.c. Lack of staff.

iv. Drug supply relateda. Drug shortageb. Unreliable suppliesc. Expired drug supplies

i. PATIENT RELATED FACTORS

a. Drug informationProper majority have no knowledge about drugs .e.g. expired medication may betaken.


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b. Misleading belief about therapyEven educated people may have certain misbelieves about certain antibioticsrelated to gastric upsets and so, and/or taking any medicine with milk, notspecified.

c. Patient demand and expectationUsually if the patient has trust in prescriber, he/she demands and expects therapyfrom the prescriber which would benefit him/her and thus, the patient showscompliance. It is much important, usually in psychiatric cases.

d. OTCA patient taking certain OTC may not get benefited, and so, when he/she visitsphysician, the physician may prescribe the same generic the patient is alreadytaking, thus leading to irrationality.

e. Self treatmentSometime a patient may start self treatment, which is irrational e.g. usingVibramycin cap and Ansid tab for tooth ache as self treatment.

f. Taking drug more than instructedIt means to take high dose intentionally to get healthier quickly. It may be lifethreatening if the drug is potent.

g. Inappropriate route of administrationIt may be very hazardous to administer parentral by the patient him/her self. Soskillful personnel’s are required.

ii. PRESCRIBER RELATED FACTORS

a. Lack of education and trainingLack of education and training on prescriber part is also one of the cause ofirrational drug use. For example, Tab erythromycin 250 mg t.i.d for adult isirrational.

b. Misleading belief about drug efficacyFor example, there is a general concept that citalopram enhances the suicidaltendency where as escitalopram decreases the suicidal tendency, but it is a pseudoconcept and has no justification.


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c. Lack of object drug informationIt is very important in case of potent drugs. for example, warfarin has 99%protein binding. If phenylbutazone is given simultaneously, it displaces 1%warfarin, leading to life threatening consequences.

iii. WORK-PLACE RELATED FACTORS

a. Heavy patient loadIf the number of patient is large, then the clinician may not give properconsultation time to the patient which ultimately will result in irrational drug use.

b. Lack of lab facilitiesIn remote areas, usually lab facilities are not available. Thus proper diagnosis maynot be made by the clinician and there is a chance of irrational prescription.Anyhow, if lab facilities are available and the physician does not ask for lab test,it is irrational.

c. Lack of consultation time:If there is lack of consultation staff, there will be lack of consultation time forpatient and will lead to irrational.

iv. DRUG SUPPLY RELATED FACTORS

a. Drug shortageDrug shortage may leads to drug substitute by the dispenser which is irrationalwithout the permission of physician.

b. Unreliable supplies:Unreliable drug supply at the retail pharmacy is also one of the major factorscontributing to irrational drug use.

c. Expired drug supplies:Dispensing of expired drugs also leads to irrational use of drugs. So it is theresponsibility of retail pharmacist to check the expiry date before filling aprescription. The general rule “First in, First out “should be followed to minimizethis factor.


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PROBLEMS OF IRRATIONAL DRUG USE1. Reduction in quality of drug leading to increase in diseases and high death rates2. Wastage of resources leading to reduced availability of vital drugs and increased costs.

E.g Prescribing parentral product when oral route is feasible such as prescribingaugmentin injection instead of tablets.

3. Increased risk of unwanted effects such as adverse reactions4. Development of drug resistance because basic diagnostic tests are not performed before

prescription. e.g. prescribing 3rd generation cephalosporins without performing culturesensitivity test.

5. Irrational drug use leaves negative psychological impact on the patient about therapy aswell as prescriber.

HOW TO AVOID IRRATIONAL DRUG USE

Irrational drug use can be prevented by having thorough knowledge of:

i. Generic name and cost of therapyii. Pharmacokinetics and pharmacodynamics

iii. Effectiveness of therapy in the condition being treated and its advantage over the otherdrugs.

iv. ADRs, precautions, contra indications, drug interactions and dosage regimen.v. Toxicology of drug and its treatment.

INDICATORS OF DRUG USE

WHO provided following indicators of drug use may be implemented.

1. Prescribing indicators2. Patient care related indicators3. Facility indicators

1. Prescribing indicators

The prescribing indicators include:

i. Average number of drugs per encounter.ii. % age of drugs prescribed by generic names.

iii. % age of antibiotics prescribediv. % age of injection prescribed


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i. Average no of drugs per encounterIf the prescription contains more drugs, there are more chances of drugs interactions. Inorder to minimize that risk, the average number of drugs per encounter should beminimum, making the prescription more rational.

ii. % age of drugs prescribed by generic namesUsually, there is promotional stress on the physician from pharmaceutical companies toprescribe their brands. To avoid this, WHO indicates that prescription should containdrugs by their generic names.

iii. % age of antibiotics prescribedBefore prescribing antibiotics, culture sensitivity test should be performed and thetherapy should be started with narrow spectrum antibiotics.

iv. % age of injection prescribedCost effectiveness is necessary which depends upon the route of administration.Prescription of injectable would be rational only if oral route is not feasible, otherwise itwould be irrational.

2. PATIENT CARE RELATED INDICATORS

i. Average consultation timeIf the physician does not give proper consultation time, he/she may not be able to makeproper diagnosis and thus there is a chance of irrational prescription. So due consultationtime is of extreme importance.

ii. Average dispensing timeDispensing is the responsibility of pharmacist. Less dispensing time may be due to eitherlack of knowledge or increase workload, leading to irrational use of drugs.Thus, it is the responsibility of pharmacist to give proper dispensing time to the patient,preferably using patient mother language and asking for the feedback to confirm thatpatient has understood what he/she has been told.


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SAMPLING OF DRUG USE

Definition:

“Sampling is a process by which we study a small part of a population to make judgments aboutthat population.”

Whenever we want to learn about health in the community or practices in the health system, weneed to draw samples since it would be impractical to collect data on every person or event. Indrug use surveys we need to draw samples to select facilities to survey, prescriptions to study, orpatients to observe.

So, to get a representative sample we would need to ensure that all facilities or patients can beincluded in the survey.

Sampling involves the selection of a number of study units from a defined studypopulation.

A study unit may be a person, a health facility, a prescription, or another such unit.

The study population, sometimes called the reference population, is the collection of the entirepopulation of all possible study units. Again, this population may be people, health facilities,prescriptions or other such units.

A representative sample has all the important characteristics of thepopulation from which it is drawn.

Objectives:

i. To establish efficacy of the drug.ii. To study risk aspects of the drug including both long term and short term side effects.

iii. To study risk benefit ratio of drug prescribing.iv. To study the socio-economic aspects of the drug.


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STUDY DESIGN

There are two types of approaches/study design for sampling of drug use, which are:

1. Experimental study2. Non-experimental study

1. Experimental studies

These are also called Randomized Controlled clinical trials.

In this design, the researcher controls assignment of study by random allocation of participant tothe treatment.

This design is particularly used for detection of ADRs. E.g association of clofibrate( lipidlowering agent) and cholecystitis.

2. Non-experimental studies:

These are of two types :

i. Cohort studyii. Case control study

i. Cohort study:Cohort studies are conducted to determine the agent under investigation (drug or riskfactor) for an outcome (effect or disease) . In this case, the individuals are divided intotwo groups . i.e exposed group which has exposure to the risk factor/drug and unexposedgroup which has no exposure to the risk factor and then the variable of interest (outcome/disease) is observed.For example, does exposure to smoking ( agent under investigation) associate with lungcancer ( outcome ). Such a study would recruit a group of smokers and a group of non-smokers (the unexposed group) and follow them for a set period of time and notedifferences in the incidence of lung cancer between the groups at the end of this time.

ii. Case control study:A study that compares patients who have a disease or outcome of interest (cases) withpatients who do not have the disease or outcome (controls), and looks backretrospectively to compare how frequently the exposure to a risk factor is present in eachgroup to determine the relationship between the risk factor and the disease.The goal is to retrospectively determine the exposure to the risk factor of interest fromeach of the two groups of individuals: cases and controls. These studies are designed toestimate odds.


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Case control studies are also known as "retrospective studies" and "case-referent studies

SAMPLE SIZE

The appropriate sample size depends on:• Expected variation of the data:The more variation the larger sample required.• The expected rate of the variable: For example, a smaller sample will be required toobtain the same degree of accuracy if the rate of antibiotic prescribing is 50% than if therate is 15%.• The degree of accuracy required: The larger the sample, the less the uncertainty.

The appropriate sample size is usually a compromise between what is STATISTICALLYDESIRABLE and what is FEASIBLE.

In general, a minimum sample size is 30

SAMPLING METHODS

There are two broad types of sampling methods. These are:

• Non -- probability sampling

• Probability sampling

The method of sampling depends whether there is a sampling frame available.

If a sampling frame exists, or if it can be created, probability sampling is used.

If sampling frame is not available, probability samplings cannot be used.

A sampling frame is a list of all of the available units in the study population. If a completelisting is available, the sampling frame is identical to the study population.

It is always better to use probability sampling,because;

- Probability sampling is more effective than than non probability methods.- The results of non probability sampling methods are not valid because there is

supposition.

However, in some situations, non -probability sampling is the only possible method.


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A. NON -PROBABILITY SAMPLING METHODS

If a sampling frame is not available or it cannot be created, a non-probability sampling methodwill need to be used.

There are two common methods.

These are :

- Convenience sampling- Quota sampling.

1. Convenience Sampling is a method which refers to sampling by obtaining units orpeople who are most conveniently available, at the time of data collection. Conveniencesamples are least reliable but normally the cheapest and easiest to conduct.

2. Quota sampling is a method by which different categories of sample units are includedto ensure that the sample contains units from all these categories. For example, a quotasample of patients from a health center that might included 10 patients with AcuteRespiratory Infection, 10 with diarrhea, and 10 with malaria.

Non-probability sampling is not necessarily representative of the reference population.

However, we often need to use these methods ;

- when we have inadequate record sample frames- or when a time constraint exists.-B. PROBABILITY SAMPLING METHODS

If a sampling frame (a list of the population units) exists then probability sampling may be used.

Whenever possible, use probability sampling to obtain results which are not less biased. Thereare a number of different methods.

Probability sampling involves RANDOM selection procedures toensure that each sample unit is chosen on the basis of CHANCE.

1. Simple Random Sampling

This is the simplest form of simple probability sampling. A lottery is an example of a randomsample. The simple random sampling procedure is as follows:


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a) Make a numbered list of all units in the reference population from which you will select thesample (for example, a list all the health centers in the country)

b) Decide on the size of the sample (for the WHO Drug Use Indicators method this would be aminimum of 20 facilities).

c) Choose the facilities to include by a lottery method. (For example the numbers of all thefacilities can be placed in a box and drawn, a random number table can be used, or randomnumbers can be generated using a spreadsheet or calculator.

2. Systematic Sampling

In systematic sampling, samples are randomly selected from a list of entire population at aregular interval.

To calculate the sampling interval, divide the size of the list by the desired sample size.

For example, if we want to select 20 health centers from a list of 46 in our sampling frame, oursampling interval would be 46/20 = 2.3.

It means all the 46 have 2.3 times chance of selection in the list.

3. Stratified Sampling

The population is broken down into particular groups sharing common factors and participantsare selected randomly from these groups in the appropriate proportions.

For example, this would might be the case in a study which included urban and rural facilities,facilities with or without doctors, male or female patients.

When stratified sampling is used, the sample frame (the list of the overall population) is dividedinto two or more groups. These different strata (groups) may then be sampled either randomly orsystematically.

The WHO manual recommends the use of stratified systematic sampling methods for selectingfacilities. For example, the sampling frame might include the following list of facilities.

Fascilitynumber

1 2 3 4 5 6 7 8 9 10

Type Urban Rural Rural rural Urban Rural Urban Urban Rural Rural

This could then be grouped and sorted into 2 strata as follows:


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Fascilitynumber

1 5 7 8

Type Urban Urban Urban Urban

and a sample would be selected separately from both the urban list and the rural list.

4. Clustor Sampling

In a clustor sample, a group of sample units is selected together, rather than each unit beingselected separately.

The recommended EPI WHO sampling procedure of selecting 30 groups of 7 children is acommon cluster sampling method.

Advantages

- Easy to use.- Simpler to organize.

Disadvantage

The samples selected may be less representative especially when the number of clusters selectedis low.

5. Multistage Sampling

When the two or more sampling methods are combined, then t is called multistage sampling. Forexample, we might wish to select 32 health facilities in 56 districts of Pakistan, each of whichcontains a number of health facilities. From the 56 districts, 16 districts would first be selected.In each district two health facilities would then be randomly selected. This would be two stagerandom sampling.

By :

Iftikhar Ahmad (E)

Session 2009-14

Fascilitynumber

2 3 4 6 9 10

Type Rural Rural Rural Rural Rural Rural

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Rational Drug Use