OverVIEW

PENELITIAN KEDOKTERAN

AWAL
KONTRAK PERKULIAHAN #1

NAMA MATA Metodologi Penelitian &

KULIAH Pengembangan Proposal
KODE MATA
...
KULIAH
SKS 3 (dua)
SEMESTER V (lima)
PJMK Dra. Ani Margawati,PhD

Prof.Dr.dr. Hertanto W Subagio,MS,Sp.GK

DR. dr. Awal Prasetyo, M.Kes, Sp.THT-KL
DOSEN Prof. Dr. dr. Suprihati, Sp.THT
PENGAMPU Dra. Ani Margawati,PhD
Dr. Hari Peni, MKEs, Sp
Dr.dr. Tri Laksana N, M.Kes, Sp.M
KONTRAK PERKULIAHAN #2

HARI
Jumat / 08.00 – 09.40
PERTEMUAN /JAM

TEMPAT
Ruang B 116 & B117
PERTEMUAN

Memberikan wawasan & pengetahuan mengenai

pengembangan proposal serta implikasinya pada
kemampuan mahasiswa dalam pembuatan proposal
MANFAAT penelitian. Diharapkan pula peserta mempunyai
MATA KULIAH pemahaman dan ketrampilan tentang cara menyusun
proposal penelitian pada berbagai bab &
melakukan critical appraisal terhadap tulisan ilmiah
hasil penelitian.

DESKRIPSI Penjelasan ‘Overview Penelitian di Bidang Ilmu

PERKULIAHAN Kedokteran’ dan penugasan-penugasan.
KONTRAK PERKULIAHAN #3

Setelah menyelesaikan mata kuliah ini mahasiswa

TUJUAN diharapkan mampu memahami ‘Overview Penelitian
INSTRUKSIONAL di Bidang Ilmu Kedokteran', mampu melakukan critical
UMUM appraisal terhadap tulisan ilmiah hasil penelitian, dan
membuat proposal penelitian.
KONTRAK PERKULIAHAN #4

Setelah mengikuti M.K. ini mahasiswa akan dapat:

• Menentukan topik dan judul penelitian
• Membuat ‘Pendahuluan’
• Membuat ‘Tinjauan Pustaka’
• Membuat ’Metode Penelitian’
• Membuat PKM Proposal
TUJUAN • Membuat ‘Hasil Penelitian’
INSTRUKSIONAL
KHUSUS • Membuat ‘Pembahasan’
• Membuat ‘Daftar Pustaka’
• Menguraikan konsep dan strategi critical appraisal
• Melakukan critical appraisal terhadap suatu publikasi
ilmiah hasil penelitian
• Melakukan review critical appraisal antar individu
dalam dinamika kelompok
KONTRAK PERKULIAHAN #5

Penerapan beragam metode & media pendidikan.

STRATEGI
Metode kuliah: ceramah, diskusi & penugasan
PERKULIAHAN
(misalnya review hasil penelitian).

Buku/bacaan pokok dalam perkuliahan ini adalah:

• Sudigdo Sastroasmoro. 2002 atau cetakan terbaru.
MATERI/BACAAN Dasar-dasar Metodologi Penelitian Klinis.
PERKULIAHAN • Watik Pratiknya. Metode Penelitian Kesehatan.
• E book tentang desain penelitian
• Panduan PKM Dikti 2016

• Setiap bacaan harus sudah dibaca sebelum

mengikuti kuliah.
• Evaluasi tengah semester: menilai tingkat
TUGAS pengetahuan dari bahan perkuliahan.
• Evaluasi akhir semester: gabungan nilai
kemampuan kognitif & nilai terhadap tugas-tugas
review yang dilaksanakan selama perkuliahan
KONTRAK PERKULIAHAN #6

A =4
B =3
C =2
D =1
E =0
Pembobotan
KRITERIA Syarat Kehadiran = 75%
PENILAIAN Evaluasi tengah semester = 25%
Evaluasi akhir semester + Tugas = 75%

NB:
Proposal PKM P terkirim (dengan
bukti) nilai minimal B
KONTRAK PERKULIAHAN #6

Membuat proposal penelitian individu berupa

PKM P sesuai dengan kisi-kisi di
http://simbelmawa.ristekdikti.go.id/Docs/
pengumuman/Pedoman-PKM-201
Membuat proposal penelitian individu berupa
PKM P sesuai dengan kisi-kisi di
http://simbelmawa.ristekdikti.go.id/Docs/peng
TUGAS INDIVIDU umuman/Pedoman-PKM-2017Membuat
proposal penelitian individu berupa PKM P
sesuai dengan kisi-kisi di
http://simbelmawa.ristekdikti.go.id/Docs/peng
umuman/Pedoman-PKM-2017-belmawa.pdf
Mengirimkan PKM P sesuai batas akhir PKM
Dikti
Membuat proposal KTI, akan direview secara
acak (Minggu ke-11 dst).
KONTRAK PERKULIAHAN #6

Tiap kelompok terdiri dari maksimal

5 mahasiswa
Tiap kelompok membuat ‘critical appraisal’ 2
(dua) artikel dari jurnal (observasional dan
TUGAS
eksperimental)
KELOMPOK
Dalam diskusi panel (Minggu ke-9 dst), akan
ditunjuk beberapa kelompok secara
acak/sistematis untuk presentasi critical
appraisal terhadap jurnal tersebut.
 Flowchart: Steps in the
development of a health
systems research
1
proposal
2

3
 What is the What Why do we want
to carry out the
problem and information is research? What do
why should it available? we hope to
be studied? achieve

1 2 3
Research
Methodolog
y
• variables
• types of study (study design)
• data collection techniques
• sampling
• plan for data collection
• plan for data processing and analysis
• ethical considerations
• pre-test or pilot study
Study
Design
The aim of study design is:

• To maximise attribution (inferences),

(assigning some quality)
• To minimise all sources of error,

• To be practical.
Factor to be aware of ..

• Bias
– source: systematic error,

• Confoundings
– source: a variable which is associated
with both exposure (intervention) and
outcome,

• Chance
– source: random error.
Types of study designs:
from descriptive studies to
randomized controlled trials
Types of Studies

Descriptive Studies

Observational Analytic Studies

◦ Cross Sectional studies
◦ Case Control studies
◦ Cohort studies

Experimental Studies
◦ Randomized controlled trials
Hierarchy of Study Types

Descriptive Analytic
•Case report
•Case series
•Survey Observational Experimental
•Cross sectional •Randomized
•Case-control controlled trials
•Cohort studies

Strength of evidence for causality between a risk factor and outcome

Descriptive studies
Getting a “lay of the land”
◦ Surveys (NHIS, MCBS)
◦ “How many men in the U.S. filled Viagra
prescriptions in 2004?”
Describing a novel phenomena
◦ Case reports or case series
◦ Viagra-associated serous macular detachment.
◦ Sildenafil-associated non arteritic anterior
ischemic optic neuropathy.
Descriptive studies
Cannot establish causal relationships

Still play an important role in describing trends

and generating hypotheses about novel
associations

The start of HIV/AIDS research

◦ Squamous cell carcinoma in sexual partner of Kaposi sarcoma
patient. Lancet. 1982 Jan 30;1(8266):286.
◦ New outbreak of oral tumors, malignancies and infectious
diseases strikes young male homosexuals. CDA J. 1982
Mar;10(3):39-42.
◦ AIDS in the "gay" areas of San Francisco. Lancet. 1983 Apr
23;1(8330):923-4.
Analytic Studies

Attempt to establish a causal link between

a predictor/risk factor and an outcome.

You are doing an analytic study if you have any of

the following words in your research question:
◦ greater than, less than, causes, leads to,
compared with, more likely than,
associated with, related to, similar to,
correlated with
Research Question

Is the regular consumption of Red Bull

associated with improved academic
performance among U.S. medical students?
Rationale

“Functional drink” designed for periods of

mental
and physical exertion.

◦ performance, concentration, memory,

reaction time, vigilance, and emotional
balance

Taurine + glucuronolactone + caffeine

Background

Alford C, Cox H, Wescott R. The effects of red bull energy drink on human
performance and mood. Amino Acids. 2001;21(2):139-50.
Warburton DM, Bersellini E, Sweeney E. An evaluation of a caffeinated taurine
drink on mood, memory and information processing in healthy volunteers without
caffeine abstinence. Psychopharmacology (Berl). 2001 Nov;158(3):322-8.
Seidl R, Peyrl A, Nicham R, Hauser E. A taurine and caffeine-containing drink
stimulates cognitive performance and well-being. Amino Acids. 2000;19(3-4):635-
42.
Horne JA, Reyner LA. Beneficial effects of an "energy drink" given to sleepy
drivers. Amino Acids. 2001;20(1):83-9.
Kennedy DO, Scholey AB. A glucose-caffeine 'energy drink' ameliorates subjective
and performancedeficits during prolonged cognitive demand. Appetite. 2004
Jun;42(3):331-3.
Great idea, but how do you get
started….

Interesting, novel, and relevant, but…

You only have 25,000 dollars to start

investigating this question.

What is feasible?
 DESAIN STUDI
CROSS SECTIONAL
Cross-sectional study of medical
students taking USMLE Step 2

Questionnaire administered when registering for

USMLE 2

Primary predictor:
◦ self-report of >3 cans Red Bull per week for the previous
year
Covariates:
◦ Age, sex, undergraduate university, place of birth

Outcome: Score on USMLE Step 2

Cross-sectional study:
structure

Red Bull
consumption

USMLE
Score

(ONE)
Time
 Measures of association

Disease (UMSLE Score) Prevalence

Ratio
A
Yes No A+B
C
C+D
Yes A B
Risk
Factor
(RB
Consumption) No C D
Cross-sectional Study:
Descriptive value:
◦ How many UCSF medical students drink Red Bull?
◦ What is the age & sex distribution of UCSF medical
students who drink Red Bull?
Analytic value:
◦ Is there an association between regular Red Bull
consumption and test scores among UCSF med
students?
◦ Univariate
◦ Multivariate (controlling for “confounders”)
Cross-sectional Study:
Pluses

+ Prevalence (not incidence)

+ Fast/Inexpensive - no waiting!
+ No loss to follow up
+ Associations can be studied
Cross-sectional study:
minuses
Cannot determine
causality
Red Bull
consumption

USMLE Score

(ONE)
Time
Cross-sectional study:
minuses
Cannot study rare outcomes

• ACE inhibitor use and hospitalization rates

among those with heart failure

• Heart failure patients with a documented DNR

status and mortality

(ONE)
Time
Cross-sectional study:
minuses

Cannot determine causality

Cannot study rare outcomes

What if you are interested in
the rare outcome?

The association between regular Red Bull

consumption and…
◦ A perfect score on the USMLE – Step 2
◦ Graduating top 1% of the medical school
class
◦ Acceptance into a highly selective residency

ANSWER: A Case-Control
study
 DESAIN STUDI
KASUS KONTROL
Kasus Kontrol

Contoh
Kasus :
mahasisma kedokteran tahun ke-4 diterima residensi di
“spesialisasi penyakit dalam”
Kontrol :
mahasisma kedokteran tahun ke-4 yang melamar
namun tidak diterima.
Prediktor : konsumsi Red Bull secara reguler
(dilaporkan sendiri oleh subyek)
Additional covariates:
Age, sex, medical school, undergraduate institution
Case control studies

Investigator works “backward”

(from outcome to predictor)

Sample chosen on the basis of outcome

(cases), plus comparison group (controls)
Case-control study structure

Present
ACTUAL CASES
TARGET CASES
mahasisma kedokteran
Medical students
tahun
Red Bull accepted to
ke-4 diterima residensi di
highly selective
consumption
residencies
“spesialisasi penyakit
YES
dalam”
Red Bull
consumption ACTUAL CONTROLS
TARGET CONTROLS
NO mahasisma kedokteran
All unsuccessful
tahun ke-4
applicants to highly
selective
yang residency
melamar namun
programs
tidak diterima
Time
 Measures of association

Disease Odds of
exposed:
Yes No not exposed

Case = A:C
Control = B:D
Yes A B
Exposure Odds Ratio
=
A:C
-------=
No C D B:D

AXD
-------
BXC
Case control studies

Determines the strength of the association

between each predictor variable and the
presence or absence of disease.

Cannot yield estimates of incidence or

prevalence of disease in the population
(why?)

Odds Ratio is
Case-control Study:
pluses

+ Rare outcome/Long latent period

+ Inexpensive and efficient: may be only
feasible
option
+ Establishes association (Odds ratio)
+ Useful for generating hypotheses
(multiple risk factors can be explored)
Case-control study:
minuses
Causality still difficult to establish
▪ Selection bias (appropriate controls)
Caffeine and Pancreatic cancer in the GI clinic
▪ Recall bias: sampling (retrospective)
Abortion and risk of breast cancer in Sweden
▪ Cannot tell about incidence or prevalence
▪ Studies of diagnostic tests:
Sensitivity, specificity
Positive predictive value, negative predictive value
Desain Studi Kohort
Melibatkan kelompok subyek, diikuti dari waktu ke
waktu.
Ada dua tujuan:
1)deskriptif
2)analitik.

▪Kohort prospektif yang klasik (peneliti

mendefinisikan sampel & mengukur variabel
prediktor, menentukan waktu tindak lanjut untuk
mengamati outcome)
▪Kohort retrospektif (yang menghemat waktu dan
uang karena masa tindak lanjut & outcome telah
terjadi saat studi berlangsung))
▪Nested kasus-kontrol (yang sangat efisien).
▪Studi Kohort-multipel & Kontrol Eksternal
Desain Studi Kohort

Studi Kohort Prospektif

Studi Kohort Retrospektif
Studi ‘Nested’ Kasus-kontrol
Studi Kohort-multipel & Kontrol Eksternal
STUDI KOHORT
PROSPEKTIF
Elemen penting pada
studi kohort

1)Seleksi sampel dari populasi

2)Pengukuran variabel prediktor pada sampel
3)Mengikuti populasi selama periode waktu
tertentu
4)Pengukuran variabel outcome
GAMBAR 7. Dalam sebuah studi kohort prospektif, peneliti (a) memilih
sampel dari populasi (garis putus-putus yang menandakan besarnya ukuran
dan tidak terdefinisi) (b) mengukur variabel prediktor (apakah ada faktor
risiko/faktor risiko positif [diarsir gelap]) , dan (c) mengukur variabel outcome
selama masa follow-up (apakah suatu penyakit ada/terjadi/muncul [dikotak
tebal]).
Struktur Studi Kohort Prospektif
1) Pasang Kohort. Pada 1976,
peneliti memperoleh daftar perawat
berusia 25-42 th di 11 negara &
mengirimkan undangan untuk
berpartisipasi sebagai kohort.
SEKARAN
G DATANG
2) Ukur Variabel
Prediktor dan Potensial
Perancu. Kuesioner BB,
olahraga & faktor risiko
potensial lain, 121.700
perawat.
3) Tindak Lanjuti Kohort
dan Ukur Outcome.
Kuesioner periodik
termasuk pertanyaan
tentang kejadian outcome
penyakit.
Studi tentang kesehatan perawat memeriksa kejadian dan faktor risiko penyakit umum pada
Contoh studi kohort
prospektif
MASA
Uji hipotesis: kenaikan
BB meningkatkan risiko
wanita kanker payudara.
Wanita BB pada 18 th
kuesioner awal & BB saat. KANKER
Mengikuti 95% wanita & PAYUDARA
1.517 kasus kanker
payudara dikonfirmasi 12
th ke depan. Wanita yang
lebih berat berisiko lebih
tinggi & BB-nya bertambah
lebih dari 20 kg sejak usia
18 tahun memiliki
peningkatan risiko 2X lipat
terkena kanker payudara
(RR = 2,0; CI 95%, 1,4-
2,8). WAKTU TIDAK KANKER
PAYUDARA
 Measures of association

Relative Risk:
Disease
A
Yes No A+B
C
C+D
Yes A B
Risk
Factor
No C D
 Kekuatan dan kelemahan
▪ Strategi yang kuat menilai insiden (jumlah kasus
baru dari suatu kondisi dalam interval waktu
tertentu).
▪ Sangat membantu menyelidiki penyebab potensial
dari kondisi outcome.
▪ Mengukur tingkat prediktor sebelum hasil terjadi,
menetapkan urutan waktu dari variabel dan
mencegah pengukuran prediktor dipengaruhi oleh
pengetahuan tentang outcome.
▪ Memungkinkan peneliti mengukur variabel lebih
lengkap & akurat daripada retrospektif.
 Kekuatan dan kelemahan

▪ Semua kohort = kerugian umum studi observasional

(relatif terhadap uji klinis): lemahnya inferensi
kausal.

▪ Interpretasinya tertutupi atau tercemari variabel

perancu.

▪ Biaya & ketidakefisienan untuk mempelajari hasil yang

langka (jarang/langka pada suatu periode tertentu,
sejumlah besar orang harus diikuti dalam jangka waktu
lama untuk mengamati hasil yang cukup/outcome
Desain kohort menjadi lebih efisien manakala outcome
yang berarti).
terjadi lebih umum/sering dan segera/cepat terjadi.
STUDI KOHORT
RETROSPEKTIF
GAMBAR 8. Pada penelitian kohort retrospektif, peneliti (a) mengidentifikasi
kohort yang telah dirancang di masa lalu, (b) mengumpulkan data pada
variabel prediktor (diukur di masa lalu), dan (c) mengumpulkan data pada
variabel outcome (diukur saat kini).

Struktur Studi Kohort

 1) Identifikasi Kelompok yang
Sesuai/cocok. Penduduk
Contoh studi kohort
Minnesota. Database Dx 1980- retrospektif
1995 = 133 Dx. Aneurysma aorta.

MASA SEKARAN
LALU G

Outcome: Risiko
pecahnya aneurysma
2) Kumpulkan Data aorta dalam 5 th
Variabel Prediktor.
sebesar 20%,
Meninjau catatan pasien RUPTUR ANEURYSMA
perempuan 6,8X lebih
untuk mengumpulkan data
mungkin ruptur AORTA
jenis kelamin, usia, ukuran dibanding laki-laki
aneurysma & faktor risiko (95% CI, 2,3-20). 31%
penyakit kardiovaskular aneurysma diameter
pada saat diagnosis. >6 cm ruptur dibanding
<4 cm (tidak ruptur).

3) Kumpulkan Data Outcome Selanjutnya.

Data catatan medis dari 133 pasien untuk
menentukan apakah aneurysma pecah atau
telah diperbaiki dengan operasi. WAKTU TIDAK
RUPTUR
Riwayat penyakit aneurisma aorta toraks dan faktor risiko terjadinya ruptur, suatu studi menganalisis data catatan medis dari
133 pasien yang memiliki aneurisma.
 Kekuatan dan kelemahan

▪ Kekuatan sama dengan kohort prospektif.

▪ Keuntungan: jauh lebih murah & menghabiskan sedikit

waktu.
▪ Subyek sudah dirancang, pengukuran baseline telah
dibuat, periode tindak lanjut telah terjadi.
▪ Kerugian utama: kontrol terbatas terhadap sampling
populasi & terhadap sifat dan kualitas variabel prediktor.

Data yang ada mungkin tidak lengkap, tidak akurat,

atau diukur dengan cara yang tidak ideal untuk menjawab
pertanyaan penelitian.
 RANDOMIZED
CONTROLLED TRIALS
Randomized controlled
trials
Investigator controls the predictor variable
(intervention or treatment)
Major advantage over observational studies is
ability to demonstrate causality
Randomization controls unmeasured confounding
Only for mature research questions
 Basic Trial Design
Populati
Populati Treatment DxNo Dx
on
on

Sampl
Sampl Randomizatio
Randomizatio
e n
n
Control
Placebo DxNo Dx
 Measures of association
Relative Risk:
Disease A
Yes No A+B
C
C+D

Yes A B
Risk
Factor
No C D
Steps in a randomized
controlled trial
1. Select participants
◦ high-risk for outcome (high incidence)
◦ Likely to benefit and not be harmed
◦ Likely to adhere
2. Measure baseline variables
3. Randomize
◦ Eliminates baseline confounding
◦ Types (simple, stratified, block)
Steps in a randomized
controlled trial
4. Blinding the intervention
◦ As important as randomization
◦ Eliminates
◦ co intervention
◦ biased outcome ascertainment
◦ biased measurement of outcome
5. Follow subjects
◦ Adherence to protocol
◦ Lost to follow up
6. Measure outcome
◦ Clinically important measures
◦ Adverse events
What is Blinding?

Single
Single blind
blind -- participants
participants are
are not
not aware
aware
of
of treatment
treatment group
group
Double
Double blind
blind -- both
both participants
participants and
and
investigators
investigators unaware
unaware
Triple
Triple blind
blind -- various
various meanings
meanings
◦◦ persons
persons whowho perform
perform tests
tests
◦◦ outcome
outcome adjudicators
adjudicators
◦◦ safety
safety monitoring
monitoring group
group
Why blind?: Co interventions

□ Unintended effective interventions

■ participants use other therapy or change
behavior
■ study staff, medical providers, family or
friends treat participants differently
□ Nondifferential - decreases power
□ Differential - causes bias
Why
Why blind?:
blind?: Biased
Biased Outcome
Outcome
Ascertainment
Ascertainment oror adjudication
adjudication
IfIf group
group assignment
assignment is is known
known
◦◦ participants
participants may
may report
report symptoms
symptoms or or outcomes
outcomes
differently
differently
◦◦ physicians
physicians oror investigators
investigators may
may elicit
elicit symptoms
symptoms or or
outcomes
outcomes differently
differently
◦◦ Study
Study staff
staff or
or adjudicators
adjudicators may
may classify
classify similar
similar events
events
differently
differently in
in treatment
treatment groups
groups

Problematic
Problematic with
with “soft”
“soft” outcomes
outcomes
◦◦ investigator
investigator judgement
judgement
◦◦ participant
participant reported
reported symptoms,
symptoms, scales
scales
Analysis of randomized
controlled trial
Analyzed like cohort study with RR
Intention to treat analysis
◦ Most conservative interpretation
◦ Include all persons assigned to intervention
group (including those who did not get treatment
or dropped out)
Subgroup analysis
◦ Groups identified pre-randomization
TUGAS
Individu
Membuat PKM-Proposal sesuai pedoman PKM Dikti
2017
Membuat proposal KTI
Kelompok
Membuat ‘critical appraisal’
 Thank you

Dr. dr. Awal Prasetyo, M.Kes,

Sp.THT-KL