Rianto SetiabudyDept. of Pharmacology FKUI

The Launching of IONI

Jakarta, 26 October 2009

Background Irrational use of medicines is a global

problem The examples of this problem:

o Polypharmacyo The use of medicines that are not related to the

diagnosiso Unnecessary use of expensive medicineso Inappropriate use of antibiotics

• The purpose of this discussion is to recognize factors which may hamper the implementation of RUM and to set up strategy to apply it

Outlines

Factors influencing the use of medicine How to critically appraise new drugs? Steps toward the rational

pharmacotherapy

Factors influencing the use of medicine (1)Intrinsic factors:

Do we provide adequate training for the medical students in the Rational Use of Medicine (RUM)?

Drug information:The main source of drug information for the practicing

doctorsWhat do we need? Drug information which is

objective, informative, systematic, and comprehensible (preferably not in local language)

Factors influencing the use of medicine (2)The working group:

Cooperation with industry → “local policy”Conflict of interests

The working environment:The “negative and positive goalkeeper”Overburdened health workers: information for

patients?Poorly maintained equipments

Factors influencing the use of medicine (3)The demand of patients:

Request for injectionReject generic drugsRequest for “patent” or expensive drugsRefill of prescriptionRequest for antibiotics, vitamins, “brain energizers”

The attractiveness of new drugs

Why are doctors inclined to prescribe new drugs?

Introduction of new features The launching of new drugs large

scientific events Image as up-to-date doctors The presence of cases who failed to

respond to the existing treatments Rewards Curiosity

The selling points of new drugs

Better efficacy Better tolerability More simple dosing regimen Shorter treatment period Others:

Less complications Less likely occurrence of resistance Better QOL Better laboratory results

How to critically appraise claim of new drugs?

1. The availability of clinical data: Sample size is adequate? Derived from peer-reviewed journals? Is data from meta-analysis available? Position is clear ? (As adjuvant? For

new cases? Mono therapy? For complicated cases?)

How to critically appraise new drugs?

2. Serious side effects The rarely occurring SAEs are usually not

detectable in the pre-marketing clinical trials

They are usually detected in the post-marketing surveillance

Anasarca and new oral antidiabetic

How to critically appraise new drugs?

3. New drugs appear to have less side effects: This may not be true simply because the

drug is still new In contrast, old drugs with a long list of

side effects may not be necessarily dangerous in reality

E.g.: aspirin, paracetamol, amoxicillin

How to critically appraise new drugs?

4. Long-term side effects are still unknown: The safety and efficacy data of new

drugs are derived from the relatively short clinical trials

Drugs for long-term use require special precaution, e.g. anti-glaucoma, antihypertensive agents, anti arrhytmics, oral hypoglycemic agents, NSAIDS, etc.

QT interval prolongation

How to critically appraise new drugs?

6. Understanding the dramatic reduction of complications associated with a new drug:A new drug is often claimed capable of a

dramatically reduce the complication as compared to that of the conventional treatment. This should be critically assessed.

For example: A study shows that using the conventional drug, the incidence of stroke is 2% per year.

Using the new drug, the incidence of stroke is only 1% per year.

This a 50% reduction (looks very impressive!)

How to critically appraise new drugs? The Relative Risk Reduction (RRR)= 50%But:

The Absolute Risk Reduction (ARR) is 1% (!)More interestingly:

NNT = 1 : ARR = 1 : 1% = 100 means that we have to treat 99 patients to protect only 1 patient from being hit by stroke. The 99 patients take the drug for nothing.

How to critically appraise new drugs?

7. The new drug still works in cases which already failed to respond to other agents: If this occurs, it does not necessarily

mean that this new drug is more effective than the conventional agents because the contrary is also true.

Example: antihypertensive agents

How to critically appraise new drugs? (2)

8. Real clinical benefit felt by the patient: claims of superiority of new drugs should

be sensible by the patient, e.g. reduction of case fatality rate, sequelae, length of hospitalization, risk of amputation, walking distance, etc.

Improvement of various markers is only clinically meaningful if they correlate well with the clinical improvement , e.g. HbA1c, LDL cholesterol, sputum conversion, etc.

How to consistently maintain RUM with regards to the introduction of new drugs? (1)

1. Do not prescribe a drug because of it is new, but because of it is safe, effective, suitable, and affordable

2. Appraise critically the claim of efficacy and safety of new drugs

3. Use EBM as the foundation to prescribe new drugs

4. Assess whether the price of a new drug is worth its superiority

How to consistently maintain RUM with regards to the introduction of new drugs? (1)

5. Find out whether the new drug is a “me-too drug”

6. In general, it is usually wise to wait for a while before one start prescribing new drugs

7. In contrast: do not hesitate to abandon poor old drugs, when the better new ones are available

Steps towards the rational pharmacotherapy (1)

The PROSPECT approachProblem identificationObjective of treatmentSuitable choice of treatmentPrescribing of the drug(s)Education and informationCheck, termination or modification of

treatment

Steps towards the rational pharmacotherapy (2)

Problem identification:One problem may be caused by different etiologies which

require different approaches. E.g., cough could be due to:o Excessive smokingo Chronic obstructive pulmonary disease (COPD)o Asthma o Heart failureo Tuberculosiso Captopril o Malignancies, etc.

Steps towards the rational pharmacotherapy (3)

Patient’s problems are not only confined to complaints due to disease. It may also be related to the need of prophylaxis, sickness certificate, refill of prescription, side effect, etc.

Failure to correctly identify the patient’s problem and establish the diagnosis may lead to irrational use of drugs

Steps towards the rational pharmacotherapy (4)

Objective(s) of treatment:Different problem leads to different objectives/

approach. E.g.:o Excessive smoking → stop the habit o Chronic obstructive pulmonary disease (COPD) →

oxygen, ipratropiumbromideo Asthma → bronchodilator, steroid o Heart failure → diuretics, captopril, spironolactoneo Tuberculosis → antituberculosis agents

Steps towards the rational pharmacotherapy (5)

Suitable choice of drug treatment for individual patients:4 factors to be considered (de Vries et al, 1994):1. Efficacy2. Safety3. Suitability4. Cost

This should be applied at the stage when doctor want to determine the group of drug and the specific drug in the group

Steps towards the rational pharmacotherapy (6)

DRUG EFFICACY SAFETY SUITABILITY COST

chloramphenicol +++ ++ + ++++thiamphenicol ++ +++ + ++amoxicillin ++ ++++ ++++ ++++ciprofloxacin +++ +++ - ++++ceftriaxone +++ +++ - ++

Question: a 32-yr old woman is suffering from typhoid fever. She is not hospitalized and being on her 16th week of pregnancy. What is the most appropriate anti-typhoid drug for her?

Steps towards the rational pharmacotherapy (7)

Education and informationEducation and information for the patient is of paramount important to maintain patient compliance

Check, termination or modification of treatmentDrug treatment cannot be left open endedThe doctor needs to evaluate the outcome of the

treatment, monitor it, modify or terminate it in due time

Conclusions The rational use of medicine is influenced by

many factors The objective, informative, systematic, and

comprehensible drug information is important to support the rational use of medicine

The over-enthusiasm to use new drugs may also contribute to the irrational use of medicine

The PROSPECT approach could become a practical way to implement the rational use of medicine

Thank YouThank You