PENGANTAR PRAKTIKUM EBM

Rizaldy Pinzon, MD, PhD

Email : drpinzon17@gmail.com
EVIDENCE BASED MEDICINE

¡ Iptekdok berkembang sangat

cepat
¡ Obat dan metode terapeutik
yang baru dan berkembang pesat
¡ Teknologi usang yang tidak
terbukti bermanfaat bahkan
membahayakan
EVIDENCE BASED MEDICINE

¡ Paradigma untuk menggunakan bukti ilmiah terbaik

dan terkini dalam pengambilan keputusan klinik
pada pasien sebagai individu
¡ Comtoh penerapan : evidence based clinical
practice guideline, drug formulary
EBM BUKAN :

¡ Cook book of
medicine
¡ Bukan pemangkas
biaya
PERTANYAAN

Bukti ilmiah yang dipakai dalam pengambilan keputusan klinik sebaiknya

berasal:
A. Dari penelitian hewan
B. Dari pendapat senior
C. Penelitian terkini dan terbaik
D. Pengalaman klinik
E. Pendapat pakar
TIDAK SEMUA OBAT BERMANFAAT, DAN BILA PUN
BERMANFAAT TIDAK UNTUK SEMUA ORANG
PARADOKS DI BIDANG OBAT

¡ Tidak semua obat bermanfaat

¡ Bila bermanfaat, tidak buat semua orang
¡ Ada manfaat kecil, dan pemakaian jangka panjang
(kapan mau berhenti)
¡ Aspek biaya dan efektivitas
PERTANYAAN

Langkah pertama dalam praktek evidence based medicine adalah:

A. Melakukan pelacakan bukti ilmiah
B. Telaah pustaka
C. Analisis kritis hasil penelitian
D. Mengajukan pertanyaan klinik
E. Menghitung risiko relative suatu penelitian
¡ Langkah awal :
mengajukan pertanyaan
yang dapat dijawab
¡ Mencari jawaban melalui
bukti ilmiah yang terbaik
dan terkini
¡ Melakukan telaah kritis
¡ Membuat keputusan
¡ Melakukan evaluasi
ASKING ANSWERABLE QUESTION
PERTANYAAN YANG DAPAT DIJAWAB

¡ P: populasi : siapa populasinya

¡ I/ E : intervensi / eksposur : obat/ device
¡ C: comparison : obat standar/ plasebo
¡ O: outcome : kematian/ kesakitan
PERTANYAAN

Pemberian candesartan dibandingkan dengan captopril pada hipertensi untuk

mencegah stroke pada usia tua. Langkah pertama yang mereka lakukan adalah
menentukan komponen PICO (Populasi, Intervensi, Control, dan Outcome)
untuk kata kunci. Komponen P untuk populasi yang diperlukan sebagai kata
kunci adalah:
A. Usia tua
B. Penderita hipertensi usia lanjut
C. Pasien stroke
D. Candesartan
E. Kematian dini
PERTANYAAN

Komponen I untuk intervensi yang diperlukan sebagai kata kunci adalah:

A. Captopril

B. Usia lanjut

C. Hipertensi

D. Stroke

E. Candesartan
PERTANYAAN

Komponen O sebagai outcome/ luaran klinik yang diperlukan sebagai kata

kunci adalah

A. Stroke

B. Hipertensi usia lanjut

C. Kematian dini

D. Captopril

E. Harga yang murah

PERTANYAAN

Bukti ilmiah dengan derajat hirarki yang tertinggi adalah:

A. Pendapat pakar
B. Laporan kasus
C. Studi quaei ekperimental
D. Kajian sistematis dan meta analisis
E. Uji klinik randomisasi buta ganda
 Table 4 – Comparison of the scorecards for medi- to
cations A and B. for
Th
Value Criterion Medication A Medication B pra
Co
Efficacy High Moderate
inj
Risk Moderate High
sat
Net cost Neutral Unfavorable
wo
Societal benefit High Low
(to
Overall value High Low
P&
par
tio
medications were antineoplastic drugs,
• Untukand four
terapi, makawere monoclo-
pilihan bukti ilmiah P&
nal antibodies approved for different
terbaikindications. The review/
adalah : systematic other an
medications were an immunosuppressant, anRCTs
meta-analysis antidote, a local
atau individual per
RCT One was requested for
anesthetic, and an intravenous analgesic. Co
• Meta analysis
an unlabeled indication. The average lebih baik
medication cost for an val
episode (e.g., cycle of chemotherapy) of treatment in this group the
was $17,699 (median $8,305, range $45–$94,500). Co
Two examples illustrate how the value model was applied to att
¡ Apakah penelitian ini
valid: dikerjakan dengan
kaidah ilmiah yang baik
¡ Bila valid, apakah
hasilnya penting ?
¡ Dapatkah diaplikasikan
pada setting kita ?
PERTANYAAN

Syarat utama suatu artikel penelitian tentang terapi dinyatakan valid adalah:
A. Double blind
B. Follow up lengkap
C. Intention to treat analysis
D. Randomisasi
E. Dibandingkan plasebo
SYARAT VALIDITAS SUATU ARTIKEL TERAPI

¡ Apakah dilakukan randomisasi

¡ Apakah pengukuran luaran objektif/ blind ?
¡ Apakah follow up lengkap ?
¡ Apakah dilakukan analisis intention to treat analysis ?
¡ Apakah baseline characteristic serupa ?
“IF IT’S NOT WRITTEN DOWN, IT
DIDN’T HAPPEN, AND IF YOU CAN’T
FIND IT WITHIN 1 HOUR IT
DOESN’T EXIST”
QUALITY IN CLINICAL RESEARCH

¡ Clinical trial: an experiment to

determine whether the product is safe
and effective
¡ Statistical sampling (random) of a target
population
¡ Unbiased observations about product
effect (endpoint) and AE collection and
reporting
QUALITY: WHY WE CARE ?

¡ Lack of quality can lead to underestimation or

overestimation of true treatment effect

¡ Quality can influence the accuracy of safety

reporting

¡ Label: FDA/sponsor agreed communication with

stakeholders
WHAT ARE THE MOST IMPORTANT ASPECTS OF
CLINICAL TRIAL ?
WHAT ARE THE MOST IMPORTANT ASPECTS OF
CLINICAL TRIAL ?

¡ Two of the most important elements to the

integrity of a controlled clinical study are the
patient randomization and the treatment blinding.
¡ Effective randomization helps to balance the
known and unknown prognostic factors across
comparative groups.
¡ Treatment group imbalances within important
prognostic variables cast doubt on the primary
results at best.
RANDOMIZATION

•Why randomize

•What a random series is

•How to randomize
RANDOMIZATION

¡ Rationale

• Best way to find out which therapy is best

• Reduce risk of current and future patients of being on
harmful treatment
RANDOMIZATION

Basic Benefits of Randomization

• Eliminates assignment basis
• Tends to produce comparable groups
• Produces valid statistical tests
GOAL: ACHIEVE COMPARABLE GROUPS TO
ALLOW UNBIASED ESTIMATE OF TREATMENT

Beta-Blocker Heart Attack Trial

Baseline Comparisons

Propranolol Placebo
(N-1,916) (N-1,921)

Average Age (yrs) 55.2 55.5

Male (%) 83.8 85.2
White (%) 89.3 88.4
Systolic BP 112.3 111.7
Diastolic BP 72.6 72.3
Heart rate 76.2 75.7
Cholesterol 212.7 213.6
Current smoker (%) 57.3 56.8
RANDOMIZATION BASIS FOR
TESTS OF HYPOTHESES

• The use of randomization provides a basis

for an assumption-free statistical test of the
equality of treatments

• Such tests were originally proposed by

Fisher and are known as randomization or
permutation tests
Blinding of the trial

▪ Blinding is a procedure in which one or more

parties in a trial are kept unaware of which
treatment arms participants have been
assigned to.
▪ Blinding is an important aspect of any trial.
▪ If blinding is broken during a trial on individual
patients, it needs to be statistically and/or
ethically explained at the end.
Why do we blind?

▪ Blinding is used to prevent conscious or

unconscious bias in the design of a clinical
trial and how it is carried out.
▪ This is important because bias can affect
recruitment and allocation, care, attitudes,
assessments, etc.
▪ It is used to ensure the objectivity of trial
results
What are the potential sources of
bias in a trial?

§ Sources of bias include:

§ Patient being treated
§ Clinical staff administering treatment
§ Doctor assessing treatment
§ Team interpreting trial results
Who can be blinded in clinical trials?

▪ Participants in a trial
▪ Clinicians and data collectors
▪ Outcome adjudicators and
data analysts
Types of blinding

Type Description
Unblinded or All are aware of the treatment the
open label participant receives
Single blind or Only the participant is unaware of the
single-masked treatment they receive
Double blind or The participant and the clinicians / data
double-masked collectors are unaware of the treatment the
participant receives
Triple blind Participant, clinicians / data collectors and
outcome adjudicators / data analysts are
all unaware of the treatment the participant
receives.
Unblinded trial

▪ A trial in which no blinding is used and all

parties are aware of the treatment groups. Also
called open label.
§ Should be used:
§ For surgical procedures*
§ When changes in lifestyle are required
§ When endpoints are objective and cannot be
interpreted in different ways
§ For case studies with life-threatening situations
§ In post-marketing surveillance
§ When ethical considerations do not permit blinding
§ When no control group can be used
Single-blind trial

§ A trial in which one party, either the

investigator or participant, is unaware of
which treatment the participant is taking.
Also called single-masked trial.
§ Provides some control when double
blinding is impossible
§ Used when the experimental medicine
and control cannot be manufactured
identically
Double-blind trial

§ A clinical trial design in which neither the participants nor

the study staff know which participants are receiving the
experimental medicine, and which are receiving a placebo
(or another therapy).
§ Double-blind trials are thought to produce objective results,
since the expectations of the doctor and the participant do
not affect the outcome. Also called double-masked trial.
§ Best-controlled trial design
§ Decreased chance of observational bias
§ Should be used whenever possible
Triple blind

§ A triple blind trial means that patients, clinicians, data

collectors, outcome adjudicators and data analysts are
denied access to details of group assignment. This ensures
that bias for or against the tested treatment is very unlikely
to occur.
§ Medicine may still be labelled as A or B during analysis
§ The analyst is blinded as to which treatment is which
§ Helps to avoid bias in the analysis of results.
Unblinding the trial

▪ Unblinding is the disclosure of the treatment to a

participant or study team.
▪ It protects the participants in case of medical or safety
reasons.
▪ In a crossover design, the participant may only be
unblinded for the most recent dose.
▪ The protocol for unblinding should be described
upfront, and must include information about when and
by whom is to be done.
PERTANYAAN

Untuk melihat kesahihan suatu artikel kita harus melihat di bagian :

A. Judul
B. Penulis
C. Metode
D. Hasil
E. Diskusi
 PERTANYAAN
Pada studi ini, tentukan 3 syarat
utama validitas yang tercantum di
abstrak:
A. Dibandingkan placebo, parallel,
intention to treat
B. Randomised, parallel,
dibandingkan placebo
C. Randomised, controlled,
intention to treat
D. Randomised, blind, intention
to treat
E. Parallel, blind, intention to
treat
TEMUAN BUKTI ILMIAH
KESIMPULAN

¡ Praktek berbasis EBM dengan sistem kendali mutu dan biaya yang baik
diperlukan
¡ Langkah-Langkah EBM dimulai dengan mengajukan pertanyaan klinik yang
dapat dijawab
¡ Pendekatan PICO membantu kita untuk mengajukan pertanyaan klinik
yang dapat dijawab
¡ Langkah berikutnya adalah mencari dan melakukan telaah kritis, dan
kemudian mengambil keputusan