1b. CA. Causation

8/22/2019 1b. CA. Causation

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KAJIAN KRITIS HUBUNGAN KAUSAL

Bambang Udji Djoko Rianto

UNIVERSITAS MUHAMMADIYAH

YOGYAKARTA

2011


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The concepts of cause

something that brings about an effect or a result

cq. etiology, pathogenesis, or mechanisms

guiding for: prevention, diagnosis, & treatment


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Evidence that an association is cause & effect:

1. Temporality : cause precedes effect

2. Strength : large relative risk/ Odd ratio

3. Dose-response : larger exposure to cause associated

with higher rates of disease4. Reversibility : reduction in exposure associated

with lower rates of disease

5. Consistency : repeatedly observed by different

persons, places, circumstances &

times


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6. Biologic plausibility : makes sense, according to

biologic knowledge of the

time

7. Specificity : one cause leads to one effect

8.Analogy : cause-effect relationship

already established for a similar

exposure/ disease


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Types of evidence for cause-effect relationship:

Strength Design Finding

Strong Clinical trial Temporality

Cohort study StrengthCase control study Reversibility

Cross-sectional Dose-response

Aggregate risk Consistency

Case series Biologic plausibilityWeak Case report Specificity

Analogy


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Skenario klinis

kolega : - keamanan adrenergik agonis terhadap asma

- keraguan informasi: obat tersebut meningkatkanrisiko kematian

kolega lain: artikel hal tersebut terpublikasi secara luas

sering dalam praktek

bukti-bukti pada artikel cari referensi laporkan pada kolega


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INTRODUCTION

klinisi menjumpai pasien terpapar:

- intervensi medis/ medical intervention- environtmental agent

misal:

- apakah risiko abortus meningkat pada pekerja video

display terminals ?

- apakah vasectomi meningkatkan risiko Ca prostat ?


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jawaban klinisi harus mengevaluasi:

- validitas data

- kekuatan hubungan antara kausa dan outcome

- relevansi terhadap pasien


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Tabel 1. Users Guide for article about Harm

Are the result study valid ?

Primary guides:

Were there clearly identified comparison groups that were similar with respect toimportant determinants of outcome, other than the one of interest ?

Were the outcomes and exposures measured in the same way in the groups being

compared ?

Was follow- up sufficiently long and complete ?

Secondary guides:

Is the temporal relationship correct ?Is there a dose-response gradient ?

What are the resul ?

How strong is the association between exposure and outcoma ?

How precise is the estimate risk ?

Will the results help me in caring for my patients ?

Are the results applicable to my practice ?

What is the magnitude of the risk ?

Should I attempt to stop the exposure ?


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Tabel tersebut:

- mengevaluasi artikel causation

- menilai hubungan cause-effect dengan pertimbanganinformasi yang ada:

- systematic overviews ( meta analysis)

- kesimpulan terhadap bukti-bukti yang ada


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Are the results of the study valid ?Primary guides:

Were there clearly identified comparison groups that were

similarwith respect to important determinants of outcome,

other than the one of interest ?

pemilihan grup pembanding:

- berpengaruh terhadap kredibilitas hasil

dinilai berdasarkan al: design studi yang dipakai


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Tabel 2. Directions of inquiry and key methodologic strengths and weakness

for different study design

Design Starting point Assessment Strength Weaknesses

RCT exposure status adverse event status internal validity feasibility,

generalizability

Cohort exposure status adverse event status feasibility when susceptibility to

randomization threats to interal

of exposure not validity

possible

Case adverse event exposure status overcomes tem- susceptibility to

control status poral delays, threats to inter-

may only require nal validity

small sample

size


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1. RANDOMIZED CONTROLLED TRIAL (RCT)

experimental murni pasien terbagi dengan cara sama ke tiap grup

causal agent/ no causal agent follow-up

outcome: positif/ negatif

kekuatan: similaritas antar grup: +

dengan design baik, menunjukkan hubungan pentingantara agentdan outcome

jarang dipakai


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contoh: trial cardiac arrhytmia suppresion

hubungan antara obat anti aritmi:

- encainide

- flecainide mortalitas- maricizine

klinisi membatasi penggunaan obat tersebut


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2. STUDI COHORT

bila tak fisibel/ tak etis untuk randomisasi identifikasi: exposed & non exposedterhadap causal agent

follow-up

kejadian outcome


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contoh:

outcome perinatal pada anak dari pria terexposed

lead & larutan organik pada industri percetakan di

Norwegia:

- OT di kategorisasi terpapar terhadap 2 zat

- hasil: exposed group: 8 x terjadi partus pre term,tapi tak signifikan

perdarahan tractus gastrointestinal (tgi.) pada

penggunaan NSAID:- hasil: pada grup terexpose: 1,5 x non terexpose

per 1000 sampel

- jika menggunakan design RCT butuh 6.000 sampel


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pada studi cohort:

- subyek terseleksi sendiri bisa tidak similar

- hubungan NSAID & perdarahan tgi. usia dihubungkan dengan exposure confounding

factorCF)

- jika CF tak terdistribusi rata teknik statistik

- kadang-kadang imbalance tersebut bedaprognostic outcome


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3. STUDI KONTROL KASUS (CCS)

bila outcome sangat jarang, studi cohort tak fisibel

CCS lebih fisibel:- identifikasi kasus (misal: penyakit, hospitalisasi, kematian

- pilih kontrol: bukan outcome tetapi faktor-faktor yang simi-

lar dengan outcome, misal: - umur

- sex

- kondisi medis- teliti secara retrospektif: frekuensi relatif exposure terhadap

faktor kausa pada kasus dan kontrol (pembanding)


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contoh:

Hubungan o.c. dietilbestrol pada wanita hamil & adeno-

karsinoma anak wanita beberapa tahun kemudian

Prospektif: butuh > 20 tahun & ratusan ribu sampel

CCS:

- 2 grup wanita muda:

- kasus adenokarsinoma vagina (n= 8)- kontrol (n= 32)

- telusuri exposure rate terhadap obat


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4. CASE SERIES & CASE REPORT

tanpa grup pembanding/kontrol

tak sesuai sebagai primary guide

Kesimpulan:

- RCT terbaik untuk causation- terpenting: populasi kontrol yang sesuai


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Were the exposures & outcomes measured inthe same way in the group being compared ?

- pada CCs exposure: terpenting

- blinding subyek & interviewer: minimisasi bias

- kesempatan exposure: sama

- pada RCT & Cohort, outcome: terpenting


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Was follow-up sufficiently long & complete ?

Follow-up harus adekuat

Follow-up:

- hilang : validitas hasil menurun

- makin lama : sampel DO makin besar


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SECONDARY GUIDE

Is the temporal relationship correct ?

Exposure terhadap faktor kausal mendahului outcome

contoh:

- hubungan kasus bunuh diri dan obat antidepresi:

- bunuh diri pasca pemakaian obat ?- menggunakan obat oleh karena gejala psikis

memburuk ?


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Is there a dose response gradient ?

Kuantitas/durasi exposure terhadap kausal tinggi:

risiko outcome meningkat

contoh:

- risiko kematian Ca paru pria perokok meningkat

- 50% : 14 batang/hari

- 132%: 15-24 batang/hari

- 220%: 25 batang/hari


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What are the result ?

How strong is the association between

exposure & outcome ?

1. Risiko relatif (: cohort study):

- risiko/insidensi efek pada grup exposed dibagirisiko efek dalam grup non exposed

- nilai RR > 1: peningkatan risiko

- nilai RR < 1: penurunan risiko

contoh: 23/289 pria hipertensi (HT) meninggal

dibanding 3/185 non HT

RR pria HT: 4,9 dibanding non HT


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2. Odds ratio (OR, pada CCS)

- odds kasus grup exposed dibagiodds kontrol/ non exposed

- bila outcome jarang, RR=OR


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How precise is the estimate of the risk ?

- evaluasi ketepatan estimasi: confidence interval

- berdasar artikel-artikel tentang risiko


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What are the implications for my practice ?

Are the results applicable to my practice ?

Jika hasil valid extrapolasi: pasien/bidang kita Pasien/sampel kita similar ?

Ada beda penting ?

Contoh: - peningkatan Ca uteri pada pemakai hormonestrogen pasca menstruasi


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What is the magnitude of the risk ?

RR atau OR: efek terjadi > atau

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1b. CA. Causation

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