prescribing cascade and...
TRANSCRIPT
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