EVIDENCE-BASED MEDICINE

GUIDE TO CLINICAL DECISION

Jarir At Thobari
Dept. Pharmacology & Toxicology
Faculty of Medicine GMU
 PENDAHULUAN

Harus
Harus melakukan
melakukan keputusan
keputusan terapi
terapi

Ketidakyakinan
Ketidakyakinan terhadap
terhadap value
value dari
dari
masing-masing
masing-masing opsi
opsi

Variasi
Variasi terapi
terapi
 Observed false-positive rates for 24 radiologists reading 8734
mammograms. J National Cancer Institute, Vol. 94, No. 18, September 18, 2002
18
15 .9
16

14
False positive rate (%)

12 .5 12 .2
11.9
12
10 .8
10 .2
10 9 .5
9 9
8 .5
8 7.6
6 .9 6 .7 6 .5
6
5 .6
6 4 .9
5 .3
4 .4 4 .2
4
4 3 .5
2 .6 2 .7

15 7 1
61

13 1
59

64

78

82

93
79

88

89

89

98

98

1119

19 9 0
12 4

13 3

15 0

16 9

200

292

620

12 5 7
Number of mammogram interpreted by individual radiologist
Screening mammogram by radiologist
 Diagnosis of suspected TIA by general practitioners in the
community (n=512)

TIA 195 (38%)

Not TIA 317 (62%)
Migraine 52 (10%)
Syncope 48 (9%)
Possible TIA* 46 (9%)
‘Funny turn’† 45 (9%)
Isolated vertigo 33 (6%)
Epilepsy 29 (6%)
Transient global amnesia 17 (3%)
Lone bilateral blindness 14 (3%)
Isolated diplopia 4 (0.8%)
Drop attack# 3 (0.6%)
Intracranial meningioma 2 (0.4%)
Miscellaneous97 24 (5%)
Diagnosis of stroke and transient ischemic attack
 EBM for Therapy Decision

Unfortunately, many decisions are made based on

unreliable “evidence”

Expert opinion plays a heavy role in medical decision

making

Personal observation or anecdotal experience can

frequently overcome clear evidence to the contrary, tend
to overestimate efficacy
What’s new about EBM?
DECISION MAKING

Medical Training
Scientific Clinical
Pathophysiology
Information Experience
Textbooks

Postgraduate Training

Patient
Value
“Menurut pengalaman saya
selama ini, terapi tersebut sangat
baik & tidak masalah”
 What’s new about EBM?
DECISION MAKING
Searching Systematically

CURRENT
Hierarchy in evidence
BEST
Clinical
EVIDENCE Experience
Critical Appraisal

EBM
Clinical Relevance

Applicability

Patient
Value
 Evidence-Based Medicine

"the conscientious, explicit, and judicious use of current best

evidence in making clinical decisions about the care of
individual patients."

1. keahlian klinis (clinical expertise);

2. bukti-bukti ilmiah dari studi yang terpercaya
(best research evidence); dan
3. nilai-nilai yang ada pada pasien & harapan
(patient values and expectation).
9
 What is Evidence-Based Medicine?

See a patient Ask a question Seek the best evidence

Monitor the change Apply the evidence Appraise that

evidence
 Struktur pertanyaan klinik

P I C O
Patient Intervention Comparison Outcomes
Or Problem

Lama &
Common
Antibiotika Plasebo keparahan
cold
sakit
Penelusuran informasi limiah untuk mencari "evidence"

Bagaimana mengendalikan evidence

Burn your (traditional) textbooks Invest in evidence databases

• Revisi, paling tidak 1 tahun EBMR (EB-Medicine Review)

sekali Evidence-Based Medicine,
• Padat Referensi yang updated Evidence-Based Nursing,
(khususnya ttg diagnosis dan Cancerlit, Aidsline,
management) MEDLINE
Penelaahan terhadap bukti ilmiah (evidence) yang
ada

Diagnosis Terapi Prognosis Harm

USERS’ GUIDE http://www.cche.net

1. Is this study important?

2. Is this study valid?
3. Does this study apply to my patient population
Penerapan hasil penelaahan ke dalam praktek

Patient’s value and expectation

Evaluasi terhadap efficacy dan effectiveness

Current problems: no feedback (appropriate or not), no

proper communication, no incentives/disincentives
 Kategori Evidence

Meta analisis & Syst Rev Ia

Randomized Controlled Trial Ib
Non-Randomized Trial IIa
Quasi Experimental IIb
Observational study III
Expert opinion, clinical experience IV
Uji pra-klinik
Uji in vitro
 EBM for Therapy Decision

Evidence of Evidence of
No Benefit, Harm & Benefit &
Poor Value Good Value

Don’t do it Do it
Insufficient Evidence

Conservative
Celecoxib tidak lebih aman daripada NSAID

1287.pdf. BMJ VOLUME 324 1 JUNE 2002 bmj.com

 Cox-2 inhibitor, Rofecoxib: Manfaat dan Risiko

Tahun Jml kasus Publikasi Kesimpulan

2000 8076 NEJM Risiko upper GI event

Lebih ringan drpd NSAID

2001 > 28.000 Circulation Efek cardiovascular tdk

berbeda dgn NSAID

2002 > 200.000 Lancet Risiko CHD pada dosis>

25mg

2004 > 39.000 Lancet Risiko congestive heart

failure 1,5x lebih besar
daripada NSAID
30 Sept 04: rofecoxib (Vioxx) di recal di FDA
pasar antibiotika di dunia mencapai US$ 17 miliar
atau sekitar Rp 154 triliun

sekitar 40-62% unecessarily prescribed

90% pasien dengan tonsilofaringitis mendapat

antibiotika

hanya sekitar 15%-35% yang disebabkan oleh

streptokokus beta hemolitikus grup A yang
memang memerlukan antibiotika
Drugs Prescribed for ARI Patients (2009)
Type of Antibiotics
 SYSTEMATIC REVIEW
“cough,”
“cough,”“bronchitis,”
“bronchitis,”“sputum,”
“sputum,”andand
“respiratory
“respiratorytract
tractinfections.”
infections.”

RCT, semua bahasa, mulai 1966 s/d 1998

•• Antibiotic
AntibioticTIDAK
TIDAKLEBIH
LEBIHBAIK
BAIKdaripada
daripadaplasebo
plasebojika
jika
resolusi
resolusibatuk
batukdinilai
dinilaipada
padahari
hari7-11
7-11
•• RR=
RR=0.85
0.85(95%
(95%CICI0.73
0.73to
to1.00)
1.00)
•• Antibiotic
AntibioticTIDAK
TIDAKBERPENGARUH
BERPENGARUHterhadapterhadap
penyembuhan
penyembuhan(RR=(RR=0.62;
0.62;95%CI:0.36
95%CI:0.36toto1.09)
1.09)

•• Efek
Efeksamping
sampingantibiotika:
antibiotika:19%
19%(12-36%)
(12-36%)
•• RR=
RR=1,9
1,9(95CI:1,19-3,21)
(95CI:1,19-3,21)
Gap antara kenyataan praktek
dan current best evidence
 Obsolete & abandoned clinical practice

Pemasangan
Pemasangankateter
kateterdi
dibangsal
bangsal

Pemberian
Pemberiandigitalis
digitalisper
perinfus
infusbukannya
bukannyavia
via
injection/
injection/syringe
syringepump
pump

Pemberian
Pemberianantibiotika
antibiotikaprofilaksi
profilaksidi
dibangsal
bangsal
perawatan
perawatan

Puasa
Puasapre-op
pre-oplebih
lebihdari
dari4-6
4-6jam
jam

Pemeriksaan
PemeriksaanWidal
Widaluntuk
untukdiagnosis
diagnosistyphoid
typhoid
 Terapi antibiotika tidak rasional merupakan
faktor risiko kematian pada pasien ICU

 Studi Cohort prospektif, 2000 pasien yang dirawat di ICU utk

melihat angka kematian akibat infeksi
 655 pasien infeksi dikenali secara klinis:
 442 (67.5%) community-acquired infection
 286 (43.7%) nosocomial infection
 73 (11.1%) keduanya community-acquired & nosocomial
infections
 169 (25.8%) pasien mendapat terapi awal antibiotika secara
inappropriate

Kollef et al. Chest 1999;115:462–474

Terapi antibiotika tidak rasional merupakan faktor risiko
kematian pada pasien ICU

Hospital mortality (%) Inappropriate therapy Appropriate therapy

60 p<0.001
p<0.001
50

40

30

20

10

0
All causes Infectious disease-related
Mortality type
Kollef et al. Chest 1999;115:462–474
 Terapi antibiotika secara tepat dapat menurunkan
angka kematian pasien dengan dugaan (Study 2)

• Studi prospektif, 113 pasien VAP, menilai pemanfaatan uji

mikrobiologi dlm menetapkan peresepan antibiotika &
pengaruhnya terhadap outcome klinis
• Uji Mikrobiologi meliputi:
– blood culture (78.7% kasus)
– culture of protected brush specimens (95.5% kasus)
– BAL culture (45.5% kasus)
• Sesaat stl diagnosis, terapi antibiotika empiric antibiotic diberikan
atau dimodifikasi
• Terapi antibiotika dapat diubah atas dasar hasil kultur &
susceptibility studies

Rello et al. Am J Respir Crit Care Med 1997;156:196–200

 Terapi antibiotika secara tepat dapat menurunkan
angka kematian pasien dengan dugaan (Study 2)

Mortality (%) p<0.05

40

30

20 • Excess mortality caused

by inappropriate initial
therapy was estimated
to be 21.4%
10 (95% CI, 43.2 to -0.03)

0
Appropriate initial Inappropriate initial
antibiotic antibiotic

Rello et al. Am J Respir Crit Care Med 1997;156:196–200

 Appropriate early antibiotic therapy menurunkan
angka kematian pasien dengan bloodstream infection
(Study 3)

• Telaah retrospektif thd 843 episode kultur darah positif

dari 707 pasien dgn septicaemia,
• Appropriate antibiotic therapy & angka mortalitas
akibat septicaemia dinilai 3 timepoints:
– saat inisiasi terapi empiric
– Setelah hasil kultur positif dilaporkan
– Setelah hasil pemeriksaan bakteri patogen penyebab
dilaporkan
• 78% pasien mendapat terapi antibiotik secara tepat dan
adekuat utk seluruh timepoints

Weinstein et al. Clin Infect Dis 1997;24:584–602

Appropriate early antibiotic therapy menurunkan angka kematian
pasien dengan bloodstream infection (Study 3)

Mortality (%)
35 RR = 3.18

30
RR = 2.46
25

20

15
RR = 1.0
10

5
65/620 8/31 3/9
0
Appropriate therapy Appropriate therapy Inappropriate therapy
at all timepoints only after susceptibility at all timepoints
determined
RR = relative risk of death Weinstein et al. Clin Infect Dis 1997;24:584–602
Evidence-based Clinical Practice Guideline

From research EB Guidelines

 Evidence Based Guidelines

Evidence Based
Medicine
Guidelines Systems
Critical Summaries
Synopsis

Meta Analysis Synthesis

RCT, Cohort etc Studies

 Challenge for Evidence Based Medicine

WHAT WE WHAT WE
SHOULD ACTUALLY
KNOW KNOW
 Challenge for Evidence Based Medicine

WHAT WE KNOW WHAT WE DO