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 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.

Visiting FindingsP

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Polypharmacy

Causes and Consequences

• Contributing factors

– Age

– Multiple medical conditions

– Multiple symptoms

• Consequences

– Adverse drug events

– Noncompliance– Multiple symptoms

– Copious prescribing

– Multiple providers

– Multiple pharmacies used

– Self treating

– Drug regimen changes

– Prescribing cascade

– Noncompliance

– Increased cost

Interaksi obat yang menakutkan

1. banyaknya obat baru yang informasitentang interaksinya dengan obat lain masih terbatas

2. semakin banyak obat yang dapat diperolehtanpa resep doktertanpa resep dokter

3. meningkatnya usia harapan hidupmanusia menyebabkan meningkatnyakelompok masyarakat yang membutuhkanperlakuan dengan polifarmasi.

4. Harga obat melambung yang diikuti denganiatrogenic cost

Lethal Combination of Tramadol and

Multiple Drugs Affecting SerotoninRipple 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 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 Number of DrugsDrugs

InteractionsInteractionsNumber of Number of

InteractionsInteractions

1 02 A+B 12 A+B 13 A+B A+C

B+C3

4A+B A+CA+D B+CB+D C+D

6

Potential Drug Interactions

Kaskade PeresepanPRESCRIBING CASCADEPRESCRIBING CASCADE

efek samping obatdiinterprestasikan sebagai

obat 1

Drug 1

Adverse drug effectmisinterpreted as

new medical condition

obat 2

efek samping obat

diinterprestasikan sebagai suatu kondisi klinis baru

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

Adverse drug effectDrug 2

Kaskade pengobatan di masyarakat

Nyeridengkul

OAINSNyeriNyeri

terapi ikutanSimtom baruterapiKeadaan awal

Kaskade peresepan di klinik pribadi

laksansia

dst

antasida

diarediare

ulu hatiulu hati

konstipasi

Hipertensi

remato-logis

OAINS

gastro-entero-

seranganGOUT

PSMBA

hidrokloro-Hipertensi entero-

logis

misoprostol

diare . . . . .

kloro-tiazida

IATROGENIKIATROGENIK(iatro = dokter)(iatro = dokter)

Examples of prescribing cascade

Initial

treatment

Adverse

effect

Subsequent

treatment

Non-steroidal

anti-

Rise in blood

pressure

Antihypertensive

treatmentanti-

inflammatory

drugs

pressure treatment

Thiazide

diuretics

Hyperuricaemia Treatment for

gout

Metoclopramide

treatment

Parkinsonian

symptoms

Treatment with

levodopa

2.5

3

0

0.5

1

1.5

2

2.5

none low medium high

Odds rasio padapengobatan awal dengan:� antihipertensi

sebagai terapilanjutan setelah

pemberian OAINS

� obat anti-goutsebagai terapi

0

1

2

3

4

5

6

none < 10 mg 10-20 mg > 20 mg

0

0.5

1

1.5

2

2.5

none < 25 mg 25-50 mg > 50 mg

sebagai terapi lanjutan setelah pemberian tiazid

� anti-Parkinsonsebagai terapi lanjutan setelah pemberian metoklopramide

NYERI

Retensi TD

meningkatNyeri

OAINS

Anti-

hipertensi antasidadiuretik misoprostol

Retensi cairan

meningkatNyeri

ulu hatiGGN GI TRACT

Prescribing CascadeKaskade Peresepan

Lingkaran setan …

Lansia

Bermacam-

efek samping ↑↑↑↑�Bermacam-

macam problem klinis

Poly-pharmacy

terapi lanjutan

tanda/simptom baru ?

Poli-farmasi

PAIN

fluid increase heartPUB

NSAID=Rp

ALZHEIMER

DISEASECANCER

Rp RpRp Rp

fluid

retention

increase

BP

heart

burnPUB

Iatrogenic Cost

Upaya meminimalisasi kaskade peresepan di rumah sakit

� menegakkan diagnosa kerja dengan cermat

� melakukan pendekatan non-farmakologi� menggunakan pengobatan sederhana � 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 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– 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 H2-antagonist PPI

Arthritis NSAID COXIB,

anti-TNF agentsanti-TNF agents

Mental health

TCA SSRIs, Atypical Anti-Psychotics

Women’s health

- (osteoporosis) biphosphonate

AIDS - Protease Inhibitors/cocktail

Medical OutcomesECHO Model

Clinical HumanisticEconomic

� Cure

� Comfort

� Survival

� Physical

� Emotional

� Social

� Expense

� Savings

� Cost Avoidance

outcomespharmaco-

Relationship between Outcomes, Pharmacoeconomics and Pharmaceutical Care

outcomesresearch

pharmaco-economics

pharmaceuticalcare

Definition

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

Economic

Clinical

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 identical outcomes

Economic

Clinical

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 • 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 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

Economic

Clinical

Economic

Clinical

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 I

The new treatment is The new treatment is

Less effective and more more effective and

expensive more expensive

Difference in

effects

III II

The new treatment is The new treatment is

less effective and more effective and

less expensive less expensive

The four possible qualitative results in a cost effectiveness analysis

Comparative Bioavailability Study

of Two Different Nimesulide-

Containing 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 minproduct

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 A Boutcomeoutcome

Better C Doutcome

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)

Economic

Clinical

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

Economic

Clinical

Humanistic

Cost-Benefit Analysis

• Example:

_____________________________________________

Cost Benefit Average B:C RatioCost 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• Antimicrobial agents

(antibiotics, antifungal, antiviral)

• Corticosteroids

• Antianxiety/sedative agents

**Adjuvant analgesic agents**

Outcome Measures

Disease IndicatorClinical

OutcomeHumanistic Outcome

Economic Outcome

Hypertension BP

Renal failure Stroke

MI Death

QOLCost/↓ mmHg BP

Cost/stroke avoided Cost/life year saved

DeathCost/life year saved

Hyperlipidemia LDL levelsAngina

MI Death

QOLCost/MI avoided Cost/point ↓ in LDL

DiabetesA1C

BG levels

Retinopathy Nephropathy

Death QOL

Cost/change in A1C Cost/kidney transplant avoided

AsthmaFEV,

peak flow

Exacerbation event Death

QOLCost/symptom free day

Outcome Measures

for pain management

Agent IndicatorClinical

OutcomeHumanistic Outcome

Economic Outcome

NSAID painCV event

GI event

Renal failureQOL

Cost/↓ mmHg BP

Cost/stroke avoided Cost/life year saved

CELECOXIB Less CV event QOL Cost >>

Renal failure Cost/life year saved

IBUPROFEN Better GI event QOL Cost <<

Pharmacoeconomics

++-- -- --

say YESsay YES

Now what ?Now what ?

say NOsay NO

NewNew

$$

Effectiveness

++-- -- --

__do it!do it!++++++

NewMedications

NewMedications

MOST EXPENSIVE THERAPY

THERAPEUTIC FAILURE

sekitar 90% penderita akan merasa lebih sehat

meskipun dokter tidakmelakukan sesuatumelakukan 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”

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

Aku telah memberikan obat yang aku kenal

kepada pasien yang tidak tahu apa-apa

KEBANGGAAN INDONESIA UNTUK DUNIA

Treatment cost for pneumoniaLong-term study, CCP-DPS GMU, December 1997 – March 2002

9000

12000

15000

Average standard pneumonia treatment cost (Rp)

12000

16000

Exchange rate to US$1 (Rp)

0

3000

6000

0

4000

8000

Private pharmacy Private hospital Public hospitalHealthcenter Drug store Consumer Price Index

Pharmaceutical spending, as % of total health

spending, is greatest in developing countries

Bulgaria

Norway

Netherlands

United StatesUK

DenmarkSpain

FranceItaly

Germany

Greece

Developed countries

(7 - 20%)

Transitional countries

0 10 20 30 40 50 60 70

South AfricaArgentina

JordanTunisia

ThailandIndonesia

China

Egypt

Mali

Lithuania

Slovenia

EstoniaPoland

CroatiaHungary

Czech Rep.

Bulgaria Transitional countries

(15 - 30%)

Developing countries

(24 - 66 %)

Cost-Effectiveness Analysis

Example:

_____________________________________________________

Total Cost/ Lives Saved/ Average CE

100 Patients 100 Patients Ratio

Drug A $220,000 79 $2784.81/ life

saved

Drug B $20,000 78 $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

Therapeutic Adverse effectTherapeutic effect

Adverse effect

Minimal Maximal

Maximal YesYes ?

Minimal ? No

Critical evaluation

on selecting medicine

++-- -- --

say YESsay YES

Now what ?Now what ?

say NOsay NO

NewNew$$

ADRs

Effectiveness

++-- -- --

__do it!do it!++++++

NewMedications

NewMedications

Is evidence really evidence?

The Evidence PyramidMETA-ANALYSIS

DBRCT

RCT

In vitro (“test tube”) research

Animal research

Ideas, editorials, opinions

Case reports

Case series

Case control studies

Cohort studies

Very few studies have been published at

the time of approval!

Sonata

Subutex

Synagis

Vioxx

Zyban

Cipralex

0 10 20 30 40 50

Avandia

Celebra

Nexium

Relenza

Reminyl

Sonata

Number of studies

Published studies Finished studies

Many People Involved in

Pharmaceutical Supply-Chain

Wholesalers

Insurers

CliniciansProviders

Employers

Generics

Branded Drug Cos

PBMS

Insurers

Patients

Govt’Govt’

Types of Pharmacoeconomic Analysis

Methodology Cost measurement unit

Outcome unit

Cost minimization Dollars Various- but equivalent in comparative groupsin 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 – Provider

– Patient

– Payer

– Society