Prescribing cascade and

Pharmaco-economics
Dep. Farmakologi dan Terapeutik,
Fakultas Kedokteran

Universitas Sumatera Utara

Prescription Drug Use: Harms

Medications have the potential for harm as well as
benefit and adverse drug events (ADE) are common.
An ADE is an injury from a medication.
Annually 35% of community-dwelling elders
experienced an ADE, 29% required health care
services.
Adverse drug events responsible for 5-28% of acute
hospitalizations among geriatric patients.
In nursing home residents, 51% of ADEs were found
to be preventable.

Percentage

Visiting Findings

Polypharmacy
Causes and Consequences
Contributing factors

Consequences

Age
Multiple medical conditions
Multiple symptoms
Copious prescribing
Multiple providers
Multiple pharmacies used
Self treating
Drug regimen changes
Prescribing cascade

Adverse drug events

Noncompliance
Increased cost

Interaksi obat yang menakutkan

1. banyaknya obat baru yang informasi
tentang interaksinya dengan obat lain
masih terbatas
2. semakin banyak obat yang dapat diperoleh
tanpa resep dokter
3. meningkatnya usia harapan hidup
manusia menyebabkan meningkatnya
kelompok masyarakat yang membutuhkan
perlakuan dengan polifarmasi.
4. Harga obat melambung yang diikuti dengan
iatrogenic cost

Lethal Combination of Tramadol and

Multiple Drugs Affecting Serotonin
Ripple MG. et al. Am J For Med Path. 21(4):370-4,2000

The threshold for seizures is lowered by

tramadol. In addition, the risk for seizure is
enhanced by the concomitant use of tramadol
with selective serotonin reuptake inhibitors or
neuroleptics.
The cause of death in this individual was
seizure activity complicating therapy for back
pain and depression

Potential Drug Interactions

Number of
Drugs
1
2
3

Interactions
A+B
A+B
B+C
A+B
A+D
B+D

A+C
A+C
B+C
C+D

Number of
Interactions
0
1
3

Potential Drug Interactions

Kaskade Peresepan
PRESCRIBING CASCADE
obat 1

Drug 1

Adverse drug effect

misinterpreted as
new medical condition
efek samping obat
diinterprestasikan sebagai
suatu kondisi klinis baru

obat 2

Drug 2

Adverse drug effect

efek samping obat

Rochon PA, Gurwitz JH. BMJ. 315:1096-9,1997.

Kaskade pengobatan di masyarakat

Kaskade peresepan di klinik pribadi

Keadaan awal

Nyeri
dengkul

terapi

Simtom baru

terapi ikutan

OAINS
Nyeri
ulu hati

antasida

konstipasi
laksansia
diare
dst

rematologis
serangan
GOUT

OAINS
PSMBA
gastroenterologis

hidro
klorotiazida

Hipertensi

misoprostol

diare . . . . .

IATROGENIK
(iatro = dokter)

Examples of prescribing cascade

Initial
treatment
Non-steroidal
antiinflammatory
drugs

Adverse
effect
Rise in blood
pressure

Thiazide
diuretics

Hyperuricaemia Treatment for

gout

Metoclopramide Parkinsonian
treatment
symptoms

Subsequent
treatment
Antihypertensive
treatment

Treatment with
levodopa

Odds rasio pada

pengobatan awal dengan:

antihipertensi
sebagai terapi
lanjutan setelah
pemberian OAINS

obat anti-gout
sebagai terapi
lanjutan setelah
pemberian tiazid

anti-Parkinson
sebagai terapi lanjutan
setelah pemberian
metoklopramide

2.5
2
1.5
1
0.5
0
none

low

medium

high

none

< 25 mg

25-50 mg

> 50 mg

none

< 10 mg

10-20 mg

3
2.5
2
1.5
1
0.5
0

6
5
4
3
2
1
0
> 20 mg

NYERI

OAINS

Retensi
cairan

diuretik

TD
meningkat

Anti-

hipertensi

GGN GI TRACT

Nyeri
ulu hati

misoprostol

antasida

Kaskade
Prescribing
Peresepan
Cascade

Lingkaran setan
Lansia

Bermacammacam
problem klinis

efek samping

PolyPolipharmacy
farmasi

tanda/
simptom baru ?

terapi
lanjutan

PAIN
CANCER

ALZHEIMER
DISEASE

NSAID=Rp

fluid
retention

increase
BP

PUB

heart
burn

Rp

Rp

Rp

Rp

Iatrogenic Cost

Upaya meminimalisasi kaskade

peresepan di rumah sakit

menegakkan diagnosa kerja dengan
cermat

melakukan pendekatan non-farmakologi

menggunakan pengobatan sederhana
yang efektif dengan dosis paling rendah

kurangi dosis yang diberikan

mencoba obat pilihan lain

pertimbangkan dengan seksama
penambahan obat baru yang benar-benar
dibutuhkan dan aman

Sikap Farmasis dalam menghadapi kombinasi

obat akibat kaskade peresepan
Farmasis harus peduli tentang reaksi sampingan
disamping indikasi, dosis dan cara pemberian suatu
obat
Farmasis harus peduli dengan pertambahan ragam
item obat dibandingkan dengan pada awal
pengobatan
Farmasis harus mencurigai pertambahan obat untuk
terapi simptomatis sebagai kaskade peresepan
Farmasis harus waspada terhadap interaksi obat
yang merugikan akibat kaskade peresepan
Farmasis perlu mengingatkan dokter akan
kemungkinan buruk akibat kaskade peresepan

PharmacoEconomics
Adding drugs to the formulary involves careful
consideration of:
Efficacy
Safety
Quality
Cost
Cost factors are becoming more important
Science of pharmacoeconomics is emerging
Pharmacoeconomics
Cost (total resources consumed in producing a good or
service)
Price (the amount of money required to purchase an item)

Adding drugs to the formulary

clinic

available

Introduced

GI ulcer
Arthritis

H2-antagonist
NSAID

Mental
health
Womens
health
AIDS

TCA

PPI
COXIB,
anti-TNF agents
SSRIs, Atypical
Anti-Psychotics
biphosphonate

- (osteoporosis)
-

Protease
Inhibitors/cocktail

Medical Outcomes
ECHO Model

Economic
 Expense
 Savings
 Cost
Avoidance

Clinical
 Cure
 Comfort
 Survival

Humanistic
 Physical
 Emotional
 Social

Relationship between Outcomes,

Pharmacoeconomics and Pharmaceutical Care

pharmacoeconomics

outcomes
research

pharmaceutical
care

Definition
Economic outcomes measure that focuses on
the evaluation of pharmaceutical products and
pharmaceutical services

Clinical
Economic

Humanistic

cost-minimisation

cost-benefit

Pharmacoeonomics

cost-utility

cost-effectiveness

Cost-Minimization Analysis
Compares the total relevant cost-difference
between treatment alternatives (products or
services) that are considered to produce
identical outcomes
Clinical
Economic
Humanistic

Cost-Minimization Analysis
Examples:
comparing an AB rated generic drug to its brand
name equivalent
comparing the cost of a multiple dose schedule to
a once daily schedule that is equally safe and
effective
analyzing the cost of administering and
monitoring the same drug in two different settings

Generically Equivalent
Pharmaceutically equivalent
Therapeutically equivalent
The same drug with the same effect,
but the product is from a different
manufacturer
AB rating in Orange Book

Cost-Effectiveness Analysis
Compares the total relevant cost of therapy to
the effectiveness when the outcomes for the
alternatives are NOT equal
Clinical

Clinical
Economic

Economic

Humanistic

Cost-Effectiveness

Cost-effectiveness = Good Value

Cost effective strategy may NOT save money
Saving money is NOT always cost-effective
original vs. me too

Cost-Effectiveness Analysis
Difference in costs

IV
The new treatment is
Less effective and more
expensive

I
The new treatment is
more effective and
more expensive
Difference in
effects

III
The new treatment is
less effective and
less expensive

II
The new treatment is
more effective and
less expensive

The four possible qualitative results in a cost effectiveness analysis

Comparative Bioavailability Study

of Two Different NimesulideContaining Preparations Available
on the Italian Market
V. Hutt, J. Waitzinger, F. Macchi
Clin Drug Invest 21(5):361-369, 2001.

In vitro dissolution data of Aulin and

Nimesulide Dorom tablets

Drug
product

Percentage of nimesulide
dissolved
15 min
30 min

Aulin

89.25

98.45

Nimesulide
Dorom

52.43

63.85

Plasma concentrations (arithmetic means z = terminal rate constant. SD) of

nimesulide after single oral administration of Aulin and Nimesulide Dorom
100mg to healthy volunteers (n = 18).

Cost-Effectiveness Analysis
Less $

More $

Worse
outcome

Better
outcome

Cost Utility Analysis

Evaluates the value of an intervention or a
program against the value of the outcome in
terms of quality-adjusted life years (QALYs)

Clinical
Economic
Humanistic

Cost Utility Analysis

Incremental Cost Utility Ratio (ICUR)

ICUR = Cost drug A - Cost drug B

QALY drug A - QALY drug B
QALY = length of life quality of life

Cost Utility Analysis

Example:
_____________________________________________________
Total
Years of x Utility = QALYs
CU
Cost
Life (LYs)
Ratio
Drug A
$20,000
3.5
0.75
2.6
$7619/QALY
Drug B
$16,000
2.5
0.80
2.0
$8000/ QALY
_____________________________________________________

Cost-Benefit Analysis
Evaluates the value of all resources consumed in
implementing a program or intervention
against the value of the outcome

Clinical
Economic

Humanistic

Cost-Benefit Analysis
Example:
_____________________________________________
Cost
Benefit Average B:C Ratio
New
Benefit/Cost
Service
$25,000
$45,000
1.8:1
_____________________________________________

Commonly Prescribed Drugs

Anti-inflammatory agents
Analgesic agents
Antimicrobial agents
(antibiotics, antifungal, antiviral)

Corticosteroids
Antianxiety/sedative agents
**Adjuvant analgesic agents**

Outcome Measures
Indicator

Clinical
Outcome

BP

Renal failure
Stroke
MI
Death

QOL

Cost/ mmHg BP
Cost/stroke avoided
Cost/life year saved

Hyperlipidemia

LDL levels

Angina
MI
Death

QOL

Cost/MI avoided
Cost/point in LDL

Diabetes

A1C
BG levels

Retinopathy
Nephropathy
Death

QOL

Cost/change in A1C
Cost/kidney transplant
avoided

Asthma

FEV,
peak flow

Exacerbation
event
Death

QOL

Cost/symptom free
day

Disease

Hypertension

Humanistic
Outcome

Economic Outcome

Outcome Measures
for pain management
Indicator

Clinical
Outcome

Humanistic
Outcome

Economic
Outcome

pain

CV event
GI event
Renal failure

QOL

Cost/ mmHg BP
Cost/stroke avoided
Cost/life year saved

NSAID

CELECOXIB

Less

CV event

QOL

Cost >>

IBUPROFEN

Better

GI event

QOL

Cost <<

Agent

Pharmacoeconomics
say NO

- -New
-

$$

say YES

Now what ?

+++

do it!

Medications

Effectiveness

MOST EXPENSIVE
THERAPY

THERAPEUTIC
FAILURE

sekitar 90% penderita akan

merasa lebih sehat
meskipun dokter tidak
melakukan sesuatu
oleh karena itu
pertama sekali jangan bikin celaka!

first do no harm!

Medical License
My name is Bond,
James Bond OO7,
I have License to kill
Medical profession
has a better License,
to save and
also to kill

Aku telah memberikan obat yang aku kenal

terhadap penyakit yang aku pahami
kepada pasien yang tidak tahu apa-apa

KEBANGGAAN INDONESIA UNTUK DUNIA

Treatment cost for pneumonia

Long-term study, CCP-DPS GMU, December 1997 March 2002
Average standard pneumonia treatment cost (Rp)
15000

Exchange rate to US$1 (Rp)

16000

12000

12000

9000
8000
6000
4000

3000
0

Private pharmacy
Healthcenter

Private hospital
Drug store

Public hospital
Consumer Price Index

Pharmaceutical spending, as % of total health

spending, is greatest in developing countries
Greece
Germany
Italy
France
Spain
Denmark
UK
United States
Netherlands
Norway

Developed countries
(7 - 20%)

Bulgaria
Czech Rep.
Hungary
Croatia
Poland
Estonia
Slovenia
Lithuania

Transitional countries
(15 - 30%)

Mali
Egypt
China
Indonesia
Thailand
Tunisia
Jordan
Argentina
South Africa

Developing countries
(24 - 66 %)

10

20

30

40

50

60

70

Cost-Effectiveness Analysis
Example:
_____________________________________________________
Total Cost/
Lives Saved/
Average CE
100 Patients
100 Patients
Ratio
Drug A

$220,000

79

Drug B

$20,000

78

$2784.81/ life
saved

$256.41/ life
saved
_____________________________________________________

Cost-Effectiveness Analysis
Incremental Cost Effectiveness Ratio (ICER)

ICER =

(cost of A cost of B)
(effectiveness of A effectiveness of B)

ICER = $220,000 - $20,000

79 Lives - 78 Lives
= $200,000 / live saved

pharmacotherapeutics
Adverse effect

Therapeutic
effect

Minimal

Maximal

Maximal

Yes

Minimal

No

Critical evaluation
on selecting medicine
say NO

$$
ADRs

- -New
-

say YES

Now what ?

+++

do it!

Medications

Effectiveness

Is evidence really evidence?

The Evidence Pyramid
META-ANALYSIS
DB
RCT
RCT
Cohort studies
Case control studies
Case series
Case reports
Ideas, editorials, opinions
Animal research
In vitro (test tube) research

Very few studies have been published at

the time of approval!
Cipralex
Zyban
Vioxx
Synagis
Subutex
Sonata
Reminyl
Relenza
Nexium
Celebra
Avandia

10

20

30

40

50

Number of studies
Published studies

Finished studies

Many People Involved in

Pharmaceutical Supply-Chain
Wholesalers
Providers

Clinicians

Employers
Insurers
Generics

PBMS

Branded
Drug Cos

Govt
Govt
Patients

Types of Pharmacoeconomic Analysis

Methodology

Cost measurement
unit

Outcome unit

Cost minimization

Dollars

Various- but equivalent

in comparative groups

Cost benefit

Dollars

Dollars

Cost effectiveness

Dollars

Natural units (life

years, mg/dl blood
sugar, LDL cholesterol)

Cost utility

Dollars

Quality adjusted life

years

Perspective
pharmaco-economics
The point of view considered in economic
analyses influences the outcomes and costs
considered to be most relevant:
Provider
Patient
Payer
Society