Problems associated with the implementation of the Rational Use of

							        Rianto Setiabudy
Dept. 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     Polypharmacy
     o     The use of medicines that are not related to the
           diagnosis
     o     Unnecessary use of expensive medicines
     o     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
    doctors
   What 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 injection
    Reject generic drugs
    Request for “patent” or expensive drugs
    Refill of prescription
    Request 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 approach
  Problem identification
  Objective of treatment
  Suitable choice of treatment
  Prescribing of the drug(s)
  Education and information
  Check, 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 smoking

     o Chronic obstructive pulmonary disease (COPD)

     o Asthma

     o Heart failure

     o Tuberculosis

     o 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, ipratropiumbromide
    o Asthma → bronchodilator, steroid

    o Heart failure → diuretics, captopril, spironolactone

    o 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. Efficacy
   2. Safety
   3. Suitability
   4. 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)
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?

 DRUG              EFFICACY SAFETY SUITABILITY   COST
 chloramphenicol      +++      ++       +        ++++
 thiamphenicol         ++     +++       +         ++
 amoxicillin           ++    ++++     ++++       ++++
 ciprofloxacin        +++     +++       -        ++++
 ceftriaxone          +++     +++       -         ++
Steps towards the rational
pharmacotherapy (7)
  Education and information
   Education and information for the patient is of
   paramount important to maintain patient
   compliance

  Check, termination or modification of treatment
    Drug treatment cannot be left open ended
    The 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 You