EVIDENCE BASED MEDICINE

Evidence Based Medicine (EBM)

Menggunakan segala pertimbangan bukti
ilmiah (evidence) yang sahih yang diketahui
hingga kini untuk menentukan pengobatan
pada penderita yang sedang kita hadapi.

Merupakan penjabaran bukti ilmiah lebih

lanjut setelah obat dipasarkan dan seiring
dengan pengobatan rasional.
 What is the level (L)
of evidence ? (TGA)
L1a. Randomized controlled trial (best evidence)
L1b. Meta-analysis (pros and cons)
L2. Retrospective analysis (case-control studies)
L2. Prospective follow-up (cohort studies)
Cross-sectional population (prevalence studies)
Previous reviews (position statements)
Clinical interventions (non-randomized)

A comprehensive evaluation of all data is the best

approach!
Safety data (important element !)
 How is LoE implemented in
Recommendation Guidelines? (1)
Levels of Evidence for Heart Failure:
A. Data derived from multiple RCTs.
B. Data derived from a single randomized
trial or non-randomized studies.
C. Consensus opinion of experts was the primary
source of recommendation.
 How is LoE implemented in
Recommendation Guidelines? (2)
Strength of Recommendation:
Class I: Conditions for which there is evidence/general agreement that
a given procedure/therapy is useful and effective.
Class II: Condition for which there is conflicting evidence or divergence
of opinion about the usefulness /efficacy of performing the
procedure /therapy.
Class IIa: in favor of usefulness
Class IIb: usefulness is less well established

Class III: Condition for which there is evidence/general agreement that a

procedure/therapy is not useful/effective and may be harmful.
 How is LoE implemented in
Recommendation Guidelines? (3)
The strength of evidence does not necessarily
reflect the strength of recommendation. A
treatment may be considered controversial
although it has been evaluated in CTs; conversely,
a strong recommendation may be based on years
of clinical experience and be supported only by
historical data or by no data at all.
Disini conflict of interest dari penilai dijaga ketat!!
 Drug Safety in increased focus
around the world
Increasing number of drug withdrawals because
of harmful effects (recently: Prepulsid, Posicor,
Hismanal, Rezulin, Lipobay, etc).
Scientific report on epidemic proportions of
serious ADRs in hospitalized patients. (Lazarou,
JAMA 1998)
Medical mistakes (45.000 deaths/annually) and
medication errors (28%) are reported, including
under-utilization of proven drug therapies. (US
Institute of Medicine, 2001)
 Effects of Inhaled Glucocorticoids on Bone Density in Premenopausal Women,

by Elliot Israel, M.D., Taruna R., Banerjee, M.P.H., Garrett M. Fitzmaurice, Sc.D., Tania V.
Kotlov, M.S., Karen LaHive, M.D., and Meryl S. LeBoff, M.D.;

The New England Journal of Medicine, September 27, 2001.

Background

Here is the important background information that the authors give us:

-consensus reports recommend increased use of inhaled corticosteroids

(also referred to as glucocorticoids) for patients with asthma,

-it is known that oral corticosteroids accelerate bone loss, and that
fractures occur in 30 to 50% of patients on oral corticoids,

-it is not clear, however, whether inhaled corticosteroids accelerate bone

loss.
 ES obat kronis dapat diperkirakan dari
parameter Chronicity Index
 CHRONICITY INDEX is
a measure of chronic toxicity:
LD50

Endrin :

= CI = 7

LD50
(90 hari)

120

Deksametason :

= 1714

0.07
 EBM sebenarnya merupakan cara yg biasa
dilakukan dalam proses penilaian suatu obat baru
yg akan dipasarkan. Disini malah diperlukan juga
penilaian animal dan in-vitro studies.

Perbedaannya:
* Penilaian obat pra-pemasaran
mempertimbangkan seluruh masyarakat,
* EBM menimbang untuk satu pasien.
 EBM in terms of
Benefit-Risk Ratio
The seriousness of the problem to be treated
The efficacy of the drug you intend to use
The seriousness and frequency of possible
adverse effects
The efficacy of other drugs which might be
used instead
The safety of other drugs which might be used
instead.
 Bagaimana dokter bisa mengerti
EBM ?
Evidence perlu diterapkan pada penderita dg
segala penyakit/komplikasi-nya.
Evidence berubah menurut perkembangan
ilmu.
Perlu CME model baru untuk
mensosialisasikan pengetahuan baru ini.
Forum seminar biasa tidak lagi adekuat.
Pengobatan profesional membutuhkan
paradigma baru dalam CME.
 Untuk menunjang EBM, FDA telah
melakukan perubahan label indikasi
obat sewaktu ijin pemasaran melalui
undang-undang.
Misalnya: Indikasi antibiotik yang luas, seperti
untuk upper respiratory tract infection,
terdiri dari banyak lokasi yang kuman
penyebab maupun antibiotiknya berbeda.
 Respiratory Tract Infections
(FDA Points to Consider doc.)
The terms of URTI and LRTI are being refined by more
specific infections:
5. Community-acquired pneumonia (CAP)
6. Nosocomial pneumonia
7. Acute bacterial exacerbations of chronic bronchitis
8. Secondary bacterial infections of acute bronchitis
9. Acute otitis media
10. Acute sinusitis
11. Streptococcal pharyngitis

(More indications may follow in response to industrys

marketing application of claims)
Community acquired pneumonia (1):
(FDA Points to Consider doc.)
Differentiation of CAP acc. to Label Claim:
Atypical pneumonia
Viral peumonia
Acute bacterial pneumonia
Aspiration pneumonia
Ventilator-associated pneumonia
Pneumonia in an immuno-compromised
and/or neutropenic host.
Community acquired pneumonia (2):
(FDA Points to Consider doc.)
Differentiation made for bacterial pneumonia:
Pediatric patients:
no sputum for culture
infants (3-24 mo) higher baseline value for fever
WBC count >15.000 usually assoc. with severe
infection.
Radiographic findings different, etc

Geriatric patients: ..
 Bagaimana dg penisilin G
untuk CAP tanpa penyulit?
Intravenous crystalline Pen G, 3 - 5 juta Unit,
setiap 3 jam menghasilkan C max rata-rata + 20
45 g/ml*, yaitu 10 22 kali > MIC S.
pneumoniae yg resisten, tapi tidak disebut dalam
informasi tabel tadi.
Rasio Cmax / MIC yang besar merupakan faktor
daya bunuh kuman (conc.dependant) yg ampuh.
CAP tanpa penyulit juga dianjurkan diobati di
rumah untuk menghindari nosocomial infection.
 Bagaimana interpretasi hasil Lab
yg tidak pas?
Nilai Widal yg dipakai untuk diagnosis tifus .
SGPT yg merupakan surrogate endpoint.
Hasil antibiogram yg mengikutsertakan AB yg
tidak semestinya:
gentamicin (tidak pas) untuk kuman tifus,
tidak mengikutsertakan AB terpilih seperti
flukloksasilin, dikloksasilin atau penisilin G untuk
Staph. aureus atau stretokokkus, tapi
menyertakan berbagai sefalosporin,... dsb.
 Lalu, bagaimana dg evidence pengobatan empirik yg
tidak ada uji klinik formal, tetapi sangat berguna?

Varisella: cukup mandi teratur, tidak perlu AB rutin

Parotitis epidemika: cukup permen karet.
Dikloksasilin atau flukloksasilin untuk staph. resisten,
juga penisilin prokain tidak dipakai lagi.
Probenesid (dosis kecil) telah dilupakan untk gout,
walaupun 65% merupakan masalah ekskresi asam urat
(alopurinol di-indikasikan untk masalah pembentukan
urat {35%}).
 EBM menjembatani
Ilmu Kedokteran dan Hukum ?
EBM mulai dibutuhkan juga oleh seorang
hakim menentukan apakah suatu pengobatan
tertentu sudah benar dalam persidangan.
Diperlukan ilmu (evidence) di belakang
pertimbanga suatu testimoni seorang saksi
ahli. (JAMA Vol. 283 No.21, June 2000)
Juga, EBM menentukan harga saham pabrik
obat, yang disebarkan mass media ekonomi.
Namun, masih akan dijumpai berbagai kendala,
karena ilmu pengobatan dan EBM sendiri
tidak sesederhana itu.
 EBM is challenged by the very
presence of neutraceuticals
While orthodox medicine is requiring stricter
use of drugs by scientific evidence,
unrestricted availability of alternative
methods and medicines are worldwide - most
without even any evidence of efficacy and
safety - at a price that surpass new
pharmaceuticals.
 (1) Sepuluh Pedoman Pengobatan
Rasional :
1. Timbanglah manfaat-risiko dgn
memperhitungkan prinsip Primum non nocere.
2. Gunakanlah pertama-tama obat yg paling
established, dan kenalilah obat pilihan ini untuk
setiap indikasi.
3. Gunakanlah obat pilihan yg anda ketahui paling
baik efeknya.
4. Batasilah pemberian jenis obat seminimal
mungkin
5. Sesuaikanlah dosis obat untuk setiap penderita.
 (2) Sepuluh Pedoman Pengobatan
Rasional :
6. Gunakanlah dosis efektif terkecil.
7. Pilihlah cara pemberian obat yg paling aman,
tanpa mengurangi efektivitas.
8. Jangan memilih preparat terbaru, karena
barunya.
9. Janganlah ketinggalan menggunakan obat baru
yang (lebih) baik.
10. Cocokkanlah kebenaran data promosi pabrik
obat.
 EBM is perhaps not always
applicable for many reasons:
Some times we cannot treat just the numbers.
Other times we cannot use statistics to treat a specific
patient.
Large outcome studies includes patients with uncontrollable
variables.
Controlled clinical trials are not always flawless.
Pediatric CTs have not been required until 1998, although
compulsory for adults since 1962.
Dose-finding studies are rare, not the least in pediatrics.
Ultimately: ask 3 specialists and you will get 2-3 different
answers. Equipoise of opinions should perhaps be set at
around 70 : 30, or more.
 Conclusion
Proper drug use should be promoted nationally.
Education on drugs and EBM must take a different
approach (not education by coercive,
pharmaceutical marketing needs).
The cause of irrationalism is linked with a
perpetuating error in a larger (health) system.
Health and DrugUsePolicy must be established.
If the Health Department is failing, universities
and the profession should - morally take
initiative.