Epidemiologi KlinikEpidemiologi Klinik&&

Evidence Based Evidence Based MedicineMedicine

Blok 3 FK MuhamadiyahBlok 3 FK Muhamadiyah

OlehOleh

Prof.DR.Dr.R.M. Suryadi Tjekyan Prof.DR.Dr.R.M. Suryadi Tjekyan DTM&H.MPHDTM&H.MPH

EVIDENCE BASED MEDICINE

EPIDEMILOGIKLINIK

SEBAGAI METODA

Normalitas/Normalitas/AbnormalitasAbnormalitasDiagnosisDiagnosisKekerapanKekerapanRisikoRisikoPrognosisPrognosisPengobatanPengobatanPencegahanPencegahanKausaKausaPerjalanan/Riwayat Perjalanan/Riwayat alamialami

CRITICAL APPRAISAL

GOOD AND VALID EVIDENCE

Give T=the Best to The Patients

biologic onset(patobiology)

Prognostic Factors

Diagnostic test

+ Dx

early diagnosispossible

usual clinical diagnosis •sembuh

•komplikasi•cacad•mati

Risk factors(Causation)

Screening

Clinical TrialsPrevention I

area penelitian

*Clinical TrialsTherapy

Clinical TrialsPrevention II

Diagnostic test

End Points

EPIDEMIOLOGI KLINISEPIDEMIOLOGI KLINIS Batasan epidemiologi klinis adalah studi Batasan epidemiologi klinis adalah studi

mengenai variasi luaran mengenai variasi luaran (out come)(out come) dan dan perjalanan dari penyakit pada perorangan atau perjalanan dari penyakit pada perorangan atau

kelompok dan sebab dari variasi tersebutkelompok dan sebab dari variasi tersebut. .

Evidence Based Medicine Pendekatan pada pengelolaan pasien yang mengaplikasikan informasi medis dari hasil penelitian yang sahih (The best evidence )  Give T=the

Best to The Patients

Epidemiologi Klinis Penerapan metode epidemiologi dan biostatistika pada diagnosis, terapi dan prognosis pasien

•Evidence-based medicine (EBM) is the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients (Sackett 1996). EBM bertujuan memperbaiki perawatan EBM bertujuan memperbaiki perawatan

penderita dengan carapenderita dengan cara

Penggunaan yang efisien dan efektif alat Penggunaan yang efisien dan efektif alat diagnosediagnose

Penggunaan Petanda Prognostik yang baikPenggunaan Petanda Prognostik yang baik Penggunaan metoda terapi,rehabilitasi dan Penggunaan metoda terapi,rehabilitasi dan

prevensi yang efektif dan amanprevensi yang efektif dan aman Penyesuaian yang baik tepat sesuai dengan Penyesuaian yang baik tepat sesuai dengan

yang dikehendaki penderitayang dikehendaki penderita

..

ObjectivesObjectives

1.1.Memahami dasar dasar Evidence Based Memahami dasar dasar Evidence Based MediccineMediccine

2. Memahami Health Service 2. Memahami Health Service Research(Penelitian Pelayanan Kesehatan) Research(Penelitian Pelayanan Kesehatan) sebagai sebagai bagian dari Epidemiologibagian dari Epidemiologi

3.3.Memahami batasan penyakit , sakit dan Memahami batasan penyakit , sakit dan resiko yang ditimbulkannya. resiko yang ditimbulkannya.

4.4.Memahami keadaan Normal dan Memahami keadaan Normal dan AbnormalitasAbnormalitas

5.5.Memahami Aplikasi klinis dari RR , RD dan Memahami Aplikasi klinis dari RR , RD dan NNT(Risk Ratio,Risk Difference dan Number NNT(Risk Ratio,Risk Difference dan Number Needed to treat)Needed to treat)

APA PERANAN APA PERANAN EPIDEMIOLOGI KLINIKEPIDEMIOLOGI KLINIK

Epidemiologi klinik merupakan Epidemiologi klinik merupakan metoda dasar dari EBM metoda dasar dari EBM Berupa Berupa aplikasi prinsip dan metode aplikasi prinsip dan metode epidemiologi pada epidemiologi pada permasalahan yang dijumpai permasalahan yang dijumpai dikedokteran klinik dikedokteran klinik

Dasar pendekatan kuantitatif di Dasar pendekatan kuantitatif di KlinikKlinik

..

Pengarahan bentuk interaksi klinisi dan Pengarahan bentuk interaksi klinisi dan penderitapenderita

Pendekatan lintas sektoral melalui keilmuan Pendekatan lintas sektoral melalui keilmuan dasar dasar

epidemiologi klinik pada tatanan klinikepidemiologi klinik pada tatanan klinik

Mengembangkan dan menetrapkan Mengembangkan dan menetrapkan metode metode

epidemiologi berdasar pengamatan klinik yang epidemiologi berdasar pengamatan klinik yang

akan menghasilkan kesimpulan yang sahih akan menghasilkan kesimpulan yang sahih (valid)(valid)

Fokus dari epidemiologi klinik Fokus dari epidemiologi klinik adalahadalahisu klinis berupa :isu klinis berupa :Normalitas dan AbnormalitasNormalitas dan AbnormalitasDiagnosisDiagnosisKekerapan/FrekuensiKekerapan/FrekuensiRisikoRisikoPrognosisPrognosisPengobatan/TerapiPengobatan/TerapiPencegahanPencegahanKausaKausaPerjalanan/Riwayat alamiPerjalanan/Riwayat alami

NORMALITAS & NORMALITAS & ABNORMALITASABNORMALITAS

Last (1995): Last (1995): a) Keadaan yang sesuai dengan variasi a) Keadaan yang sesuai dengan variasi

yang yang ada pada populasiada pada populasib) Normal” adalah indikasi peluang b) Normal” adalah indikasi peluang

yang yang rendah untuk mendapatkan penyakitrendah untuk mendapatkan penyakit

c) Merujuk kepada kurva normal Gauss c) Merujuk kepada kurva normal Gauss

normal adalah bila berada normal adalah bila berada dalam variasi dalam variasi

rata rata ± 2 SDrata rata ± 2 SD

NORMAL SECARA KLINISNORMAL SECARA KLINIS

Normal keadaan yang khas Normal keadaan yang khas pada populasi secara umum pada populasi secara umum Chol Chol 200mg/dl 200mg/dl

Normal dapat dindikasikan Normal dapat dindikasikan keadaan yang tidak memerlukan keadaan yang tidak memerlukan follow up lebih lanjut ataupun follow up lebih lanjut ataupun intervensiintervensi

Abnormalitas bila kadar Kolesterol > rerata + 2 x SD = > 169.9 + (2 x 33.17)=236.24

KOLESTER

240.0

230.0

220.0

210.0

200.0

190.0

180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

KOLESTERF

req

ue

ncy

10

8

6

4

2

0

Std. Dev = 33.17

Mean = 169.9

N = 50.00

Kolesterol darah

Normal secara LaboratorisNormal secara LaboratorisBiasanya dipakai interval referensi [±2 Biasanya dipakai interval referensi [±2

SD]SD]KETERBATASANKETERBATASAN

1. Asumsi data berdistribusi normal 1. Asumsi data berdistribusi normal akan akan

tetapi tidak selalau data klinis tetapi tidak selalau data klinis berdistribusi normal.berdistribusi normal.2. Pemilihan ± 2 SD adalah arbitrase 2. Pemilihan ± 2 SD adalah arbitrase mengapa tidak dipilih 90 % atau mengapa tidak dipilih 90 % atau

99 %99 %3. Tidak selalu terdapat hubungan 3. Tidak selalu terdapat hubungan

umum umum antara penyimpangan statistik antara penyimpangan statistik

dengan dengan penyakit di Klinik Anemia dan penyakit di Klinik Anemia dan

gejala gejala kliniknya ,Serum Cholesterol dan kliniknya ,Serum Cholesterol dan

MCIMCI

4. Interval referensi tergantung pada 4. Interval referensi tergantung pada populasi populasi

referensireferensi a) dapat terdapat orang yang sakit a) dapat terdapat orang yang sakit

didalammnya didalammnya b) Tidak seluruh populasi mengikuti test b) Tidak seluruh populasi mengikuti test C) Umur/Sex/Ras berpengaruh terhadap C) Umur/Sex/Ras berpengaruh terhadap

interval interval referensi referensi

5.5. Interval referensi dapat tidak Interval referensi dapat tidak memprediksi abnormalitas secara memprediksi abnormalitas secara akuratakurat

6. Limit interval referensi biasanya tidak 6. Limit interval referensi biasanya tidak tetap bergantung pada jumlah individu tetap bergantung pada jumlah individu pada ekor kurvapada ekor kurva

EBMEBMEBMEBM

Started in early 90’s by clinical epidemiologistsStarted in early 90’s by clinical epidemiologists 19921992 : only few articles on EBM: only few articles on EBM 20002000 : >1000 articles: >1000 articles IndonesiaIndonesia : started in 1997: started in 1997 WorkshopsWorkshops : Yogya (2000) : Yogya (2000)

IKA IKA FKUI (2000, 2001)FKUI (2000, 2001)

Group discussion on EBM / mailing list:Group discussion on EBM / mailing list:<ebm-f2000@yahoogroups.com> <ebm-f2000@yahoogroups.com>

(coord: <firmanda@cabi.net.id>)(coord: <firmanda@cabi.net.id>)

1200

1000

800

600

400

200

1964 -1991 1993 1995 1997 1999 2001

25 1

0

75

213

599

965865

1360 1370

MEDLINE searching results of articles containing the term“Evidence-based medicine”, 1964-2001; English language only

(Downloaded on Sept 6, 2001/SS)

Fletcher & Fletcher:Fletcher & Fletcher: CE = The application CE = The application of epidemiologic principles in problems of epidemiologic principles in problems encountered in clinical medicineencountered in clinical medicine

Sackett et al:Sackett et al: CE = The basic science for CE = The basic science for clinical medicineclinical medicine

Much resistance by expertsMuch resistance by experts EBMEBM: In principle – no one disagree: In principle – no one disagree All major medical journals have adopted All major medical journals have adopted

EBMEBM

EBM & Clinical Epidemiology

EBM & Clinical Epidemiology

Why do we need Why do we need evidence?evidence?

Why do we need Why do we need evidence?evidence?

ScienceScienceScienceScience

Resident A is neatResident A is neatResident B is neatResident B is neatResident C is neatResident C is neatetcetc

Deductive learning Inductive learning

Therefore Therefore Dr. AT is on callDr. AT is on call

Every FridayEvery FridayDr. AT is on callDr. AT is on call

Today is FridayToday is Friday

Therefore:All residents are neat

Previous practice:Previous practice:Previous practice:Previous practice:

6 yrs medicaleducation

40-50 yrsmedical practice

Problems with patients:Dx, Rx, Px

Consultant, colleaguesTextbooksHandbooks

Lecture notesClinical guidelines

CME, seminars, etcJournalsUsu. see only Results section,

or even worse, Abstract section

What is Evidence-based What is Evidence-based Medicine?Medicine?

What is Evidence-based What is Evidence-based Medicine?Medicine?

““The conscientious, explicit, and judicious use The conscientious, explicit, and judicious use of current best evidence in making decisions of current best evidence in making decisions about the care of individual patients”about the care of individual patients”

““Pemanfaatan bukti mutakhir yang sahih Pemanfaatan bukti mutakhir yang sahih dalam tata laksana pasien”dalam tata laksana pasien”

Integration of Integration of (1) physician’s(1) physician’s competence, competence, (2) valid (2) valid

evidence from studies, and evidence from studies, and (3) (3) patient’spatient’s preferencepreference

ProsPros : “ : “New paradigm in medicine”New paradigm in medicine”

“ “Extraordinary innovations, Extraordinary innovations,

only 2nd to only 2nd to Human Genome Project”Human Genome Project”

ConsCons : : New version of an old songNew version of an old song ‘‘Fair’Fair’ : : Nothing wrong with EBM, but:Nothing wrong with EBM, but:

• Be careful in searching Be careful in searching evidenceevidence• Meta-analyses, clinical trials, and all Meta-analyses, clinical trials, and all

observational studies should be critically observational studies should be critically appraisedappraised

Keyword for EBM:Keyword for EBM: • Methodological skillMethodological skill to judge the validity to judge the validity

of study reports of study reports (Re. Andersen B: Methodological (Re. Andersen B: Methodological errors in medical research, 1989)errors in medical research, 1989)

WHY EBM?WHY EBM?

1.New evidence are continuously generated 2. We usually fail to get the new evidence3. Our clinical performance deteriorates

with time (“the slippery slope”)4. Traditional CME does not improve

clinical performance5.EBM encourages self directed learning process which should overcome the

above shortages

Years after graduation

Relative% ofremainingknowledge

2 4 6 8 10 12

$100%

THE SLIPPERY SLOPE

1. 1. Formulate Formulate clinical problems in clinical problems in answerable questionsanswerable questions22. . SearchSearch thethe bestbest evidence: evidence: use internet or other on- use internet or other on-

line database for current evidenceline database for current evidence 3. Critically 3. Critically appraiseappraise the evidence for the evidence for VIAVIA

Validity Validity (was the study valid?)(was the study valid?) Importance (were the results clinically Importance (were the results clinically

important?)important?) ApplicabilityApplicability (could we (could we applyapply to our patient?) to our patient?)

4. 4. Apply the evidence to patientApply the evidence to patient5. Evaluate our performance5. Evaluate our performance

Steps in the practice of EBM Steps in the practice of EBM

DiagnosisDiagnosis(Determination of disease or problem)(Determination of disease or problem)

TreatmentTreatment(Intervention necessary to help the patient)(Intervention necessary to help the patient)

PrognosisPrognosis(Prediction of the outcome of the disease)(Prediction of the outcome of the disease)

Main areaMain area

Meta-analysisMeta-analysisClinical guidelinesClinical guidelines

Economic analysis Economic analysis Clinical decision makingClinical decision making

Cost-effectiveness analysisCost-effectiveness analysisQualitative researchQualitative research

Others:Others:

(I)(I)Formulating clinical Formulating clinical

questionsquestions

(I)(I)Formulating clinical Formulating clinical

questionsquestions

A 2-month-old infant with large VSDA 2-month-old infant with large VSD Birth weight 3.1 kgBirth weight 3.1 kg BW 3.8 kg, HR=132, RR 68BW 3.8 kg, HR=132, RR 68 Retractions (+)Retractions (+) Systolic murmur, gallop rhythmSystolic murmur, gallop rhythm HepatomegalyHepatomegaly Dx: Large VSD, CHF, FTTDx: Large VSD, CHF, FTT Definite Rx: early surgeryDefinite Rx: early surgery Alternative Rx: Drugs first?Alternative Rx: Drugs first?

Medical students:Medical students:((Background question)Background question)

Medical students:Medical students:((Background question)Background question)

What is VSD?What is VSD?How to Dx?How to Dx?What are symptoms & signs of What are symptoms & signs of

CHF CHF in infants with L-in infants with L-R shunt?R shunt?

What is the treatment?What is the treatment?

House officersHouse officers(Foreground question)(Foreground question)

House officersHouse officers(Foreground question)(Foreground question)

In infants with large VSD and CHF, In infants with large VSD and CHF, would administration of digoxin or other would administration of digoxin or other inotropic agent delay the need for inotropic agent delay the need for surgery?surgery?

In neonates born to mothers with In neonates born to mothers with history of herpes simplex infection, history of herpes simplex infection, does the administration of IVIG does the administration of IVIG (intravenous immunoglobulin) reduce (intravenous immunoglobulin) reduce the possibility of neonatal herpes?the possibility of neonatal herpes?

Other exampleOther exampleOther exampleOther example

Four elements of Four elements of good clinical question: good clinical question:

PICOPICO

Four elements of Four elements of good clinical question: good clinical question:

PICOPICOTheThe PatientPatient or or ProblemProblemTheThe InterventionInterventionComparativeComparative intervention (if intervention (if

relevant)relevant)TheThe OutcomeOutcome

A 11 year-old girl was evaluated for thyroid solitary nodule. She has been complaining of pain on palpation; other physical findings were negative. Thyroid function showed normal results. The physician was thinking about screening with ultrasound.

P: In young women with solitary thyroid nodule and normal thyroid function,

I: what is the likelihood of ultrasound C: -O: in excluding malignancy?

Question for DiagnosisQuestion for Diagnosis

A 15-month-old infant was brought for MMR vaccination. The mother inform that her daughter is very allergic to egg. Knowing that all MMR vaccine contain small amount of egg protein ovalbumin,

Question formulation:

P: In patients allergic to egg, I: does administration of MMR vaccine O: cause significant allergic reaction?

Harm

Harm

IIIISearching the Searching the

evidenceevidence

IIIISearching the Searching the

evidenceevidence

Examples of on-line Examples of on-line Journals / DatabasesJournals / DatabasesExamples of on-line Examples of on-line Journals / DatabasesJournals / Databases

http://bmj.comhttp://bmj.com http://adc/bmjjournals.cohttp://adc/bmjjournals.co

mm MEDLINE/PubMedMEDLINE/PubMed EMBASEEMBASE MDConsultMDConsult AAP Journal ClubAAP Journal Club Cochrane LibraryCochrane Library

Berlangganan peserta diberi kartu akses

Note:Note: Spelling (American / British), terminologySpelling (American / British), terminology Follow rigidly the instructions of each websiteFollow rigidly the instructions of each websiteExamples:Examples: ““host vs graft reaction” host vs graft reaction” ANDAND management management hemosiderosis hemosiderosis ANDAND thalassemia thalassemia OROR thalassaemia thalassaemia ““breast cancer” breast cancer” OROR “Ca mammae” “Ca mammae” ANDAND immunoglobulin immunoglobulin

OROR IVIG IVIG

Use keywords for searchingUse keywords for searching

IIIIIIAppraising the Appraising the

evidence:evidence:VIAVIA

IIIIIIAppraising the Appraising the

evidence:evidence:VIAVIA

VALIDITYVALIDITY: : In Methods section:In Methods section:

design, sample, sample size, eligibility design, sample, sample size, eligibility criteria criteria (inclusion, exclusion) sampling (inclusion, exclusion) sampling method, method, randomization method, randomization method, measurements, methods measurements, methods of analysis, etcof analysis, etc

IMPORTANCEIMPORTANCE: In Results section: In Results section

characteristics of subjects, drop out, characteristics of subjects, drop out, analysis, p analysis, p value, confidence intervals, etcvalue, confidence intervals, etc

APPLICABILITYAPPLICABILITY: In Discussion section + our patient’s : In Discussion section + our patient’s characteristicscharacteristics

VIAVIA

Were the subjects randomized?Were the subjects randomized? Were all subjects received similar treatment?Were all subjects received similar treatment? Were all relevant outcomes considered?Were all relevant outcomes considered? Were all subjects randomized included in the Were all subjects randomized included in the

analysis?analysis? Calculate CER, EER, RRR, ARR, and NNTCalculate CER, EER, RRR, ARR, and NNT Were study subjects similar to our patients in terms Were study subjects similar to our patients in terms

of prognostic factors?of prognostic factors?

Example: Critical appraisal for therapy

Example: Critical appraisal for therapy

II a. Meta-analysis of RCTa. Meta-analysis of RCTb. Large RCTb. Large RCT

II II a. Controlled trial without randomizationa. Controlled trial without randomizationb. Cohort, case control studies b. Cohort, case control studies

IIIIII a. Cross-sectionala. Cross-sectionalb. Case series, case reportsb. Case series, case reports

IV IV Expert opinionExpert opinion

Hierarchy/Level of evidenceHierarchy/Level of evidence

Impelentation of EBM Impelentation of EBM practice:practice:

How to get startedHow to get started

Impelentation of EBM Impelentation of EBM practice:practice:

How to get startedHow to get started 1. Teaching EBM in medical schools / PPDS1. Teaching EBM in medical schools / PPDS

• Easier than to change the already existing attitudeEasier than to change the already existing attitude• Most important Most important • May be included in formal curricula or integrated in May be included in formal curricula or integrated in

existing activities: ward rounds, on calls, case existing activities: ward rounds, on calls, case

presentations, group discussions, journal clubs, etcpresentations, group discussions, journal clubs, etc

2. Workshop for teaching staff 2. Workshop for teaching staff

3. Workshop for practitioners, incl. nurses3. Workshop for practitioners, incl. nurses

Resistance to EBM teaching Resistance to EBM teaching & learning & learning

Resistance to EBM teaching Resistance to EBM teaching & learning & learning

Rudimentary skill in critical appraisal / Rudimentary skill in critical appraisal /

methodological skillmethodological skill Limited resources, esp. time factorLimited resources, esp. time factor Lack of high quality evidenceLack of high quality evidence Scepticism toward evidence-based Scepticism toward evidence-based practicepractice ‘ ‘Happy’ with current practiceHappy’ with current practice

Development of EBM Development of EBM practicepractice

Development of EBM Development of EBM practicepractice

Passive diffusion modelPassive diffusion model Active dissemination modelActive dissemination model Coordinated implementation Coordinated implementation model:model:

# Patients & communityPatients & community# Health administratorsHealth administrators# Public policy makersPublic policy makers# Clinical policy makersClinical policy makers

Strategies for developing Strategies for developing EBM practiceEBM practice

Strategies for developing Strategies for developing EBM practiceEBM practice

Clinical guidelinesClinical guidelines Practice development leaders Practice development leaders (! Environment)(! Environment) Development unitsDevelopment units Dissemination of good Dissemination of good practicepractice NetworkingNetworking Research summariesResearch summaries Action researchAction research

Patient’s preferenceEvidence

Physician’s proficiency

Patient withproblem

Search theevidence

Criticallyappraise

the evidence

Formulatein answerable

question

Applythe evidence

Integration ofcurrent evidence

into practice

Valid, important,applicable evidence

Recent relevant literature

Sources ofevidence

Good clinicalquestion

Problemidentification

Patient

Advantages of EBMAdvantages of EBMAdvantages of EBMAdvantages of EBM

Encourages reading habitEncourages reading habit Improves methodological skill (and Improves methodological skill (and

willingness to do research?!)willingness to do research?!) Encourages rational & up to date Encourages rational & up to date

management of patientsmanagement of patients Reduces intuition & judgment in clinical Reduces intuition & judgment in clinical

practice, but not eliminates thempractice, but not eliminates them Consistent with ethical and medico-legal Consistent with ethical and medico-legal

aspects of patient managementaspects of patient management

End resultEnd

resultself directed, life-long learning attitudefor high quality medical management

ConclusionConclusionConclusionConclusionEBM is nothing more than aEBM is nothing more than a

framework of systematic use offramework of systematic use ofcurrent valid study results current valid study results

relevant to our patientrelevant to our patient

Remember, Remember, however …...however …...Remember, Remember,

however …...however …...Medicine is the science of Medicine is the science of

uncertaintyuncertainty

and the art of probabilitiesand the art of probabilities

Different aspects of clinical questionsDifferent aspects of clinical questions

• EtiologyEtiology – – how to identify causes for how to identify causes for diseasedisease

• Differential diagnosisDifferential diagnosis – how to rank – how to rank possible causes by likelihood, seriousness possible causes by likelihood, seriousness & treatability& treatability

• Diagnostic testsDiagnostic tests – how to select and – how to select and interpret diagnostic tests (either to rule in or interpret diagnostic tests (either to rule in or rule out), need to consider accuracy, rule out), need to consider accuracy, precision, acceptability, expense, safety etcprecision, acceptability, expense, safety etc

• PrognosisPrognosis – how to estimate patient’s – how to estimate patient’s likely clinical course and complications likely clinical course and complications over timeover time

• TherapyTherapy – – how to select treatments that do how to select treatments that do more good than harm and are worth more good than harm and are worth efforts & costsefforts & costs

• Prevention/screeningPrevention/screening – how to identify & – how to identify & modify risk factors for disease/diagnose modify risk factors for disease/diagnose disease earlydisease early

Four elements of a well constructed clinical Four elements of a well constructed clinical question: question: PICOPICO

P : Patient or ProblemI : InterventionC : Comparative interventionO : Outcome

Four elements of a well constructed clinical Four elements of a well constructed clinical question: PICOquestion: PICO

P I C O

Which mainintervention

am Iconsidering?

What is the alternativeto compare

with theintervention?

What can I hope

from this intervention?

How would Idescribe a group of patients

like mine?

B e b r i e f a n d s p e c i f i c

ExampleExample 1: 1:

• Female, 28 years, known to have SLE, Female, 28 years, known to have SLE, shortness of breath on exertion, swollen shortness of breath on exertion, swollen ankles at end of dayankles at end of day

• Previous pericardial effusion, Previous pericardial effusion, uncomplicated MI, taking ibuprofen for uncomplicated MI, taking ibuprofen for painful kneespainful knees

• No chest pain, fever, cough or sputumNo chest pain, fever, cough or sputum• BP 145/85 mmHg, HR regular 88 bpmBP 145/85 mmHg, HR regular 88 bpm• Elevated neck veins, fluid in lungs & third Elevated neck veins, fluid in lungs & third

heart sound but no murmursheart sound but no murmurs

EtiologyEtiology

P I C O

In youngfemale with

SLE & history of cardiac

involvement

..does givingibuprofen

…comparedwith no

ibuprofen

…lead toincreased

likelihood ofheart failure?

Differential diagnosisDifferential diagnosis

P I C O

In SLEpatients with new

onset heart failure

….with pre-existingCardiac

Involvement

….and takingand taking

NSAID

….which one Is more likelyexplanation?

PrognosisPrognosis

P I C O

In youngfemale

SLE

…doesdev’ment ofheart failure

….comparedwith no heart

failure

…lead toincreased mortality?

TherapyTherapy

In SLE patient onibuprofen

withheartfailure

…wouldremoval of

NSAIDand

additionof diuretic…

…versus NSAID

removal plusdiuretic plusACE inhibitor

…alleviate heart

failure?

P I C O

PreventionPrevention

P I C O

In SLEpatients

withheart failure

….…wouldlong-term

ACEInhibitor

…comparedwith no

ACE inhibitor

…preventrecurrence & improve

qualityof life

Example (2)Example (2)

• Female, 73 years, shortness of breath on Female, 73 years, shortness of breath on exertion, swollen ankles at end of dayexertion, swollen ankles at end of day

• previous uncomplicated MI, no beta-previous uncomplicated MI, no beta-blockers, taking ibuprofen for painful kneesblockers, taking ibuprofen for painful knees

• no chest pain, fever, cough or sputumno chest pain, fever, cough or sputum• BP 145/85mmHg, HR regular 88bpmBP 145/85mmHg, HR regular 88bpm• elevated neck veins, fluid in lungs & third elevated neck veins, fluid in lungs & third

heart sound but no murmursheart sound but no murmurs

EtiologyEtiology

P I C O

In elderlyfemale with

CHD …

..does givingibuprofen

…comparedwith no

ibuprofen

…lead toincreased

likelihood ofheart failure?

Differential diagnosisDifferential diagnosis

P I C O

In patients with new

onset heart failure

….with pre-existing

CHD

….and takingand takingNSAID…

….which one Is more likelyexplanation?

Example: PrognosisExample: Prognosis

P I C O

In elderlyfemale patients

with CHD

…doesdevelopment

of heart failure

….comparedwith no heart

failure…

…lead toincreased mortality?

Example: TherapyExample: Therapy

In CHD onibuprofen

withheartfailure

…wouldremoval of

NSAIDand

additionof diuretic…

…versus NSAID

removal ofdiuretic plusACE inhibitor

…alleviate heart

failure?

P I C O

PreventionPrevention

P I C O

In patients with

heart failure

….…wouldlong-term

ACEInhibitor…

…comparedwith no

ACE inhibitor…

…preventrecurrence & Improve

qualityof life

Problem 1 - Diagnostic testProblem 1 - Diagnostic test

• Male, 38 years, complaining of stomach pains Male, 38 years, complaining of stomach pains (again)(again)

• previously responsive to antacidspreviously responsive to antacids• you suspect you suspect H. pyloriH. pylori and suggest referring for and suggest referring for

endoscopyendoscopy• after describing what is involved, patient is not after describing what is involved, patient is not

keen and asks if there is another testkeen and asks if there is another test• you agree to find out about sensitivity and you agree to find out about sensitivity and

specificity of non-invasive testsspecificity of non-invasive tests

DiagnosisDiagnosis

in patients(men?) withrecurrentstomachcomplaintsresponsive toantacids…

…is non-invasivediagnostic test(breath test)…

…comparedwith

endoscopy…

…as sensitiveand specific atidentifying H.pylori status…

P I C O

Problem 2 - PreventionProblem 2 - Prevention

• male, 28 years, with symptoms male, 28 years, with symptoms suggestive of influenzasuggestive of influenza

• illness has caused misery, resulted in illness has caused misery, resulted in time off work (self-employed)time off work (self-employed)

• aware that elderly are vaccinated, wants aware that elderly are vaccinated, wants to know if it can benefit him next yearto know if it can benefit him next year

• you decide to look for evidence on you decide to look for evidence on efficacy of vaccine among young, healthy efficacy of vaccine among young, healthy adultsadults

PreventionPrevention

P I C O

In healthyadults…

…is influenzaimmunization

…comparedwith no

immunization

…effective inreducing incidence

of flu

Problem 3 - TherapyProblem 3 - Therapy

Infant, 13 months, experienced 2Infant, 13 months, experienced 2

attacks of febrile convulsionsattacks of febrile convulsions Variable recommendations on the use of Variable recommendations on the use of

maintenance anticonvulsantsmaintenance anticonvulsants Not sure whether to give or not in order to Not sure whether to give or not in order to

prevent further attacksprevent further attacks

TherapyTherapy

P I C O

In infantswith

repeatfebrile convulsion ..

.. is anti-convulsant

drugs…

comparedwith

no drugs

bettercontrolfurtherseizure

Problem 4 - PrognosisProblem 4 - Prognosis

• Female, 46 years, had ulcerative colitis for 11 Female, 46 years, had ulcerative colitis for 11 years, in remission at presentyears, in remission at present

• extensive involvement of colon, severe extensive involvement of colon, severe symptoms at timessymptoms at times

• not keen on surgery, but has read about not keen on surgery, but has read about possible increased risk of cancerpossible increased risk of cancer

• you agree to find out what the risk might beyou agree to find out what the risk might be

PrognosisPrognosis

P I C O

In middle-aged

women…

with historyof ulcerative

colitis…

…cf nocolitis

what isthe risk of developing

Ca

In patient with In patient with

X and X, would the X and X, would the administration of administration of

Y or Y, decrease the Y or Y, decrease the likelihood of likelihood of developingdeveloping

so and so?so and so?

Concluding remark

HYPOTHESIS TESTING HYPOTHESIS TESTING & &

ESTIMATION ESTIMATION (P value & Confidence (P value & Confidence

Interval)Interval)

S

Sample is assumed to be representative Sample is assumed to be representative to the population. to the population.

In research: measurement are In research: measurement are alwaysalways done in the sample, done in the sample, the results will be applied to population.the results will be applied to population.

P P

S

Target populationAccessible population

IntendedSample

Actualstudy subjects

Target population Accessible population(+ time, place)

IntendedSample

Actualstudy

subjects

Usu. based on practicalpurposes

Appropriatesampling technique

[Non-response, drop outs,withdrawals, loss to follow-up]

(Demographic & clinical)

[Subjects selectedfor study]

Subjectscompletedthe study

Target populationAccessible population

IntendedSample

Actualstudy

subjects

External validity II:Does AP represent TP?

[External validity I:Does IS represent AP?}

[Internal validity: does ASS represent IS?]

USE LOGIC / COMMON SENSE

• The provided worksheets are only one of the approaches in critical appraisal• Complete appraisals should include all aspects of research methods• Do not forget 7 points to establish cause-effect relationship (Bradford Hill)

• Correct temporal relationship• Dose dependent• Strong association• Consistency within the study (subgroup)• Coherence• Similarity to other studies• Biologically plausible

PS

Investigation

S

Sampling

P valueConfidence intervals!!!

Inference

Results

R

300 220

300218

Standard, n= 5000

Experimental, n=5000

Cholesterol level, mg/dl

t = df = 9998 p = 0.0023

Clinical

Statistical

Clinical importance vs. statistical significance

Yes No

Standard 0 10

New 3 7

Fischer exact test: p = 0.212

Clinical importance vs. statistical significance

Absolute risk reduction = 30% Clinical

Statistical

Statistic and ParameterStatistic and Parameter

An observed value drawn from the sample is An observed value drawn from the sample is called called a statistica statistic (cf. statistics, the science)(cf. statistics, the science)

The corresponding value in population is called The corresponding value in population is called a a parameterparameter

We measure, analyze, etc We measure, analyze, etc statisticsstatistics and translate and translate them as them as parametersparameters

Examples of statistics:Examples of statistics:

ProportionProportion PercentagePercentage MeanMean Median Median ModeMode Difference in Difference in

proportion/meanproportion/mean

OROR RRRR SensitivitySensitivity SpecificitySpecificity KappaKappa LRLR NNTNNT

There are 2 ways in infering statistic There are 2 ways in infering statistic into parameterinto parameter

Hypothesis testingHypothesis testing p value p value Estimation:Estimation: Confidence interval (CI)Confidence interval (CI)

P Value & CI tell the same concept in different P Value & CI tell the same concept in different waysways

P valueP value

Determines the probability that the Determines the probability that the observed results are caused solely by observed results are caused solely by chance chance (probability to obtain the observed (probability to obtain the observed results if Ho were true)results if Ho were true)

Confidence IntervalConfidence Interval

Estimates the range of values Estimates the range of values (parameter) in the population using a (parameter) in the population using a statistic in the sample (as point estimate)statistic in the sample (as point estimate)

Most commonly used CI:Most commonly used CI:

CI 90% corresponds to p 0.10CI 90% corresponds to p 0.10 CI 95% corresponds to p 0.05CI 95% corresponds to p 0.05 CI 99% corresponds to p 0.01CI 99% corresponds to p 0.01

Note:Note: p value p value only for analytical studies only for analytical studies CI CI for descriptive and analytical studies for descriptive and analytical studies

How to calculate CIHow to calculate CI

General Formula:General Formula:

CI = p CI = p Z Z x SE x SE

p = point of estimate, a value drawn from p = point of estimate, a value drawn from sample (a statistic)sample (a statistic)

ZZ = standard normal deviate for = standard normal deviate for , if , if = = 0.05 0.05 Z Z = 1.96 ( = 1.96 (~ 95% CI)~ 95% CI)

Example 1Example 1

100 FK-Unsri students 100 FK-Unsri students 60 females (p=0.6) 60 females (p=0.6)

What is the proportion of females in Indonesian What is the proportion of females in Indonesian FK students? (assuming FKUnsri represents FK in FK students? (assuming FKUnsri represents FK in Indonesia)Indonesia)

Example 1Example 1

7050106010

5096160100

40609616095

.;...

...

....%

npqSE(p)CI

x

xCI

Examples 3: CI of difference between Examples 3: CI of difference between proportions (p1-p2)proportions (p1-p2)

50 patients with drug A, 30 cured (p1=0.6)50 patients with drug A, 30 cured (p1=0.6) 50 patients with drug B, 40 cured (p2=0.8)50 patients with drug B, 40 cured (p2=0.8)

29.0;11.0)09.02.0();9.02.0()pp(CI%95

09.050

4.0

50

)2.08.0(

50

)4.06.0(

n

qp

n

qp)pp(SE

)pp(xSE96.1)pp()pp(CI%95

21

2

21

2

1121

212121

Example 4: CI for difference between Example 4: CI for difference between 2 means2 means

Mean systolic BP:Mean systolic BP:

50 smokers50 smokers = 146.4 (SD 18.5) mmHg= 146.4 (SD 18.5) mmHg

50 non-smokers50 non-smokers = 140.4 (SD 16.8) mmHg= 140.4 (SD 16.8) mmHg

xx11-x-x22 = 6.0 mmHg = 6.0 mmHg

95% CI(x95% CI(x11-x-x22) ) = (x= (x11-x-x22) ) 1.96 x SE (x 1.96 x SE (x11-x-x22))

SE(xSE(x11-x-x22) ) = S x V(1/n= S x V(1/n11 + 1/n + 1/n22))

Example 4: CI for difference between Example 4: CI for difference between 2 means2 means

V

0.13;0.1)53.3X96.1(0.6CI%95

53.350

1

50

17.17)xx(SE

7.1798

2.1649)6.1849(s

)2nn(

s)1n(s)1n(s

21

21

222

211

Other commonly supplied CIOther commonly supplied CI

Relative risk Relative risk (RR)(RR)Odds ratioOdds ratio (OR)(OR)Sensitivity, specificitySensitivity, specificity (Se, Sp)(Se, Sp)Likelihood ratio Likelihood ratio (LR)(LR)Relative risk reduction Relative risk reduction (RRR)(RRR)Number needed to treat Number needed to treat (NNT)(NNT)

In contrast to CI for proportion, mean, diff. In contrast to CI for proportion, mean, diff. between proportions/means, where the between proportions/means, where the values of CI are symmetrical around point values of CI are symmetrical around point estimate, CI’s for RR, OR, LR, NNT are estimate, CI’s for RR, OR, LR, NNT are asymmetrical because the calculations asymmetrical because the calculations involve involve logarithmlogarithm

Examples Examples

RR RR = 5.6 = 5.6 (95% CI = 1.2 ; 23.7)(95% CI = 1.2 ; 23.7)OR OR = 12.8 = 12.8 (95% CI = 3.6 ; 44,2)(95% CI = 3.6 ; 44,2)NNT NNT = 12 = 12 (95% CI = 9 ; 26)(95% CI = 9 ; 26)

If p value <0.05, then 95% CI:If p value <0.05, then 95% CI: exclude 0 (for difference), because if A=B exclude 0 (for difference), because if A=B

then A-B = 0 then A-B = 0 p>0.05 p>0.05 exclude 1 (for ratio), because if A=B then A/B exclude 1 (for ratio), because if A=B then A/B

= 1, = 1, p>0.05 p>0.05

For small number of subjects, computer For small number of subjects, computer calculated CI may not meet this rule due to calculated CI may not meet this rule due to correction for continuity automatically done by correction for continuity automatically done by the computerthe computer

Concluding remarksConcluding remarks

p values (hypothesis testing)p values (hypothesis testing) gives you the gives you the probability that the result is merely caused probability that the result is merely caused by chance, it does not give the magnitude by chance, it does not give the magnitude and direction of the differenceand direction of the difference

Confidence interval (estimation)Confidence interval (estimation) indicates indicates estimate of value in the population given estimate of value in the population given one result in the sample, it gives the one result in the sample, it gives the magnitude and direction of the differencemagnitude and direction of the difference

Concluding remarksConcluding remarks

p value alone tends to equate statistical p value alone tends to equate statistical significance and clinical importancesignificance and clinical importance

CI avoids this confusion because it CI avoids this confusion because it provides estimate of clinical values and provides estimate of clinical values and exclude statistical significanceexclude statistical significance

whenever applicable, supply CI especially whenever applicable, supply CI especially for the main results of studyfor the main results of study

in critical appraisal of study results, focus in critical appraisal of study results, focus should be on CI rather than on p value.should be on CI rather than on p value.

Concluding remarksConcluding remarks

In appraising study results, focus In appraising study results, focus should be on confidence intervals should be on confidence intervals

rather than on p values.rather than on p values.

Diagnosis

Peniliaian hasil suatu diagnostik diekpresikan kedalam bentuk satuan nilai

1.Sensitivitas/Sensitivity 2.Spesifisitas 3.Nilai Prediksi Positif 4.Nilai Prediksi Negatif 4.Likelihood ratio +5.Likelihood ratio –( Likelihood ratio = Ratio kemungkinan )

Nilai Uji Diagnostik tergantung dari Keterandalan (reliability), Kesahihannya (validity)

Relevansinya

SENSITIVITAS adalah suatu kemampuan dari suatu tes yang memberikan hasil positif dalam suatu grup perorangan dengan suatu penyakit (Positif asli).Sensitivitas = Pr (tes + / Dx +) = a/a+cProbabilitas Test Positif +gold Standard positif

SPESIFISITAS adalah kemampuan dari suatu tes yang memberikan hasil negatif dalam suatu grup perorangan tanpa suatu penyakit (Negatif asli).Spesifisitas = Pr (tes - / Dx -) = d/b+dProbabilitas test negatif +gold standard negatif

Nilai prediksi positif atau nama lainnya Positive Predictive Value /Posterior Probability of Positive Value adalah peluang orang yang disaring sebagai positif akan mempunyai penyakit yang diskrining = a/(a+b).Nilai prediksi negatif adalah Peluang orang yang disaring sebagai negatif tidak akan mempunyai penyakit yang diskrining = d /(c+d)

Likelihood Ratio

Likelihood ratio positif adalah : Peluang mendapatkan hasil positif pada kelompok penyakit dibandingkan peluang mendapatkan hasil positif pada grup bukan penyakit.

Proporsi hasil positif grup penyakit = a/ a+b

Proporsi hasil positif grup bukan penyakit = b/b+d

Likelihood Ratio Positif = ( a / a+ b ) : (b / b + d)

Likelihood ratio negatif adalah : Peluang mendapatkan hasil negatif pada kelompok penyakit dibandingkan peluang mendapatkan hasil negatif pada grup bukan penyakit

Proporsi hasil negatif grup penyakit = c/a+c

Proporsi hasil negatif grup bukan penyakit = d/b+d

Likelihood Ratio Negatif adalah = (c/ a+c ) : d / ( b+d)

Likehood Ratio PositifLikelihood Ratio dari Test =--------------------------------- = Odd Ratio-

Likelihood Ratio Negatif

Prevalen = (a+c)/(a+b+c+d)

Tes Penyaringan

PenyakitTotal

+ -

+  -

a(positif asli)

b(positif palsu)

a+b(total tes positif)

c(negatif palsu)

d(negatif asli)

c+d(total tes negatif)

Totala+c

(total penyakit)

b+d(total bukan

penyakit)

a+b+c+d(total keseluruhan)

Sensitivitas = ( a / ( a + c )Spesifisitas = (d/ ( b + d )Akurasi = (a+d)/(a+b+c+d )

Nilai Prediksi Positif = a/ ( a+ b)Nilai Prediksi Negatif = d/( c+ d)

Likelihood Ratio Positif = ( a / a+ b ) : (b / b + d)

Likelihood Ratio Negatif adalah = (c/ a+c ) : d / ( b+d)

Kreatinin kinase

Infark miokard

Total

Ya Tidak

Positif (>80 IU)

Negatif (<80 IU)

215

15

16

114

231

129

Total 230 130 360

Sensitivitas = 215/230 x 100 = 93,5%Spesifisitas = 114/130 x 100 = 87,7%

NPP = 215/231 x 100 = 93,1 %NPN = 114/129 x 100 = 88,4 %

Pre test prevalen = ( 230/360) = 63.89 %

LR + = ( proporsi + grup pneyakit / Proporsi +Goup bukan penyakit LR + = 0,9348/0,1231 = 7,5938

LR - = ( proporsi - grup pneyakit / Proporsi -Goup bukan penyakit LR - = 0.0652/0,8769 = 0,0743

 Kreatinin kinase

Infark miokard

LikelihoodRasio

Ya Proporsi

Tidak Proporsi  

Positif > 80 IU 215 215/231 = 0,9348 16 (16/130 = 0,1231) 0,9348/0,1231 = 7,5938

Negatif < 80 IU 15 15/231 = 0,0652 114 (114/130= 0,8769) 0.0652/0,8769 = 0,0743

Total 230 130 360

LR TEST = LR+/LR- = 7,5938/0,0743 = 102,2 ----odd ratio

1. Likelihood ratio test didefinisikan sebagai rasio dari Likelihood Ratio Positif dibandingkan dengan Likelihood ratio negatif

2. Makin tinggi Likelihood ratio test makin effisien kemampuan deskrimasi dari test skrining/Daignostik

LR TEST = LR+/LR- = 7,5938/0,0743 = 102,2

Nilai likelihood ratio dari skrining adalah sama dengan odd ratio.

• pria 55 th, nyeri dada kiri, menjalar

• merokok 2 pak /hari

• T 180/110, gallop +

• kolesterol 358 mg%

• probabilitas (prates) menderita PJK 90 %

• Perlu treadmill???

Hanya kasus yang memerlukan tes diagnostik

tredmil

PJK(angiografi koroner = gold standard)

prob. pascates+

+

-

-

540

1000

360

9

91

549

451

540-----549

=

probab (prates) PJK

(pascates)

+8%

98%

98%

900 100

Sn tredmil 60% dan Sp tredmil 91%

90%

probabilitas menderita PJK dari 90% ke 98%, tidak perlu tredmil

• pria 45 th, nyeri dada kiri-

tidak khas

• merokok 1 pak /hari

• T 120/80

• lab: normal

• probabilitas (prates ) PJK 50 %

tredmil

PJK (angiografi koroner)

prob. pascates

+

+

-

-

300

1000

200

45

455

345

655

300 ----- 345

=

probab (prates) PJK

(pascates)

+37%

87%

87%

500 950

Sn tredmil 60% dan Sp tredmil 91%

50%

•probabilitas

menderita PJK

dari 50% ke 87 %,

•Perlu tredmil

=

=

Pre test validity

General General structure : 2 X 2 structure : 2 X 2

tabletableTarget disorderTarget disorder

PositivePositive

(disease)(disease)

Target Target disorderdisorder

Negative Negative

(normal)(normal)PredictorPredictor

Test Test

positivepositive

True positiveTrue positive

TPTP

aa

False False positivepositive

FPFP

bbPredictorPredictor

Test Test

negativenegative

False negativeFalse negative

FNFN

cc

True True negativenegative

TNTN

ddSensitivity, specificity, predictive values, likelihood ratios, ROC

Critical appraisalCritical appraisal

Use worksheetUse worksheetUse supporting softwaresUse supporting softwares

CAT MakerCAT MakerSave in CAT BanksSave in CAT Banks

Indonesian research report CAT Indonesian research report CAT Bank??Bank??

Is this evidence about a diagnostic test Is this evidence about a diagnostic test validvalid??

Was there an independent, blind comparison with a reference (“gold”) standard of diagnosis?Was the diagnostic test evaluated in an appropriate spectrum of patients (like those in whom we would use it in practice)? Was the reference standard applied regardless of the diagnostic test result? Was the test (or cluster of tests) validated in a second, independent group of patients?

validity

Does this (valid) evidence Does this (valid) evidence demonstrate an demonstrate an importantimportant ability ability of this test to accurately of this test to accurately distinguish patients who do and distinguish patients who do and don’t have a specific disorder?don’t have a specific disorder?

SensitivitySensitivity SpecificitySpecificity Likelihood ratiosLikelihood ratios

DiseaseDisease

(+)(+)DiseaseDisease

(-)(-)TotalsTotals

Test (+)Test (+) aa bb a+ba+b

Test (-)Test (-) cc dd c+dc+d

TotalsTotals a+ca+c b+db+da+ba+b

+c+d+c+d

a/a+c d/b+d

Probability of positive test result in patients with the disease

Probability of negative test result

in patients without the disease

Sensitivity Specificity

SnNOut

SpPIn

• SnNoutSnNout• SnNoutSnNout

Diagnostic test with a very high sensitivity , a negative result effectively rules out the diagnosis

• SpPinSpPin

Diagnostic test with a very high specificity , a positive result effectively rules in the diagnosis

a/a+b

d/c+d

DiseaseDisease

(+)(+)DiseaseDisease

(-)(-)TotalsTotals

Test (+)Test (+) aa bb a+ba+b

Test (-)Test (-) cc dd c+dc+d

TotalsTotals a+ca+c b+db+d a+ba+b

+c+d+c+d

Probability of having disease in positive test group

Probability of not having disease in negative test group

Positive predictive value

Negative predictive value

Iron deficiency anemiaIron deficiency anemiaTotalsTotals

PresentPresent AbsentAbsent

DiagDiag

nostic nostic

testtest

result result (Serum (Serum ferritin)ferritin)

(+)(+)

<65 <65 mmol/Lmmol/L

731731

aa270270

bb10011001

a+ba+b

(-)(-)

>65 >65 mmol/Lmmol/L

7878

cc15001500

dd15781578

c+dc+d

TotalsTotals809809

a+ca+c17701770

b+db+d

25792579

a+b+a+b+

c+dc+d

Sensitivity=a/a+c=90%Specificity =d/b+d=85%

Pos predictive value=a/a+b=73%Neg predictive value=d/c+d=95%

LR + = se/(1-sp)=90/15=6

Prevalence= (a+c)/(a+b+c+d)= 32%

Predictor

Outcome

Odds = ratio of two probabilitiesOdds = ratio of two probabilities Odds = p/1-p Odds = p/1-p Probability = odds/1+oddsProbability = odds/1+odds

Likelihood ratioLikelihood ratio (+): (+):

Prop (+) result in people with the diseaseProp (+) result in people with the disease

Prop (+) result in people w/out the Prop (+) result in people w/out the diseasedisease

Pretest Odds X LR = Posttest OddsPretest Odds X LR = Posttest Odds

TestTest

CA B

pretest probability

0 .10 .20 .30 .40 .50 .60 .70 .80 .90 1

do not test

do nottreat

do not test

do nottreat

do not test

get on with treatment

do not test

get on with treatment

Likelihood ratio

posttest probability

TestTest

+ = Se/(1-Sp)(1-Se)/Sp= -

PreTest odds x LR

pretest probability

Pretest probability

Likelihood ratio

Posttest probability

Accuracy of the testAccuracy of the test The accuracy of the test The accuracy of the test

depends on how well the depends on how well the test separates the group test separates the group being tested into those being tested into those with and without the with and without the disease in questiondisease in question

Accuracy is measured by Accuracy is measured by the area under the ROC the area under the ROC curve. An area of 1 curve. An area of 1 represents a perfect test; represents a perfect test; an area of 0.5 represents an area of 0.5 represents a worthless test (AUC)a worthless test (AUC)

0.90-1.00 = excellent 0.90-1.00 = excellent (A) (A)

0.80-0.90 = good (B) 0.80-0.90 = good (B) 0.70-0.80 = fair (C) 0.70-0.80 = fair (C) 0.60-0.70 = poor (D) 0.60-0.70 = poor (D) 0.50-0.60 = fail (F)0.50-0.60 = fail (F)

Is the diagnostic test available, affordable, Is the diagnostic test available, affordable, accurate, and precise in our setting? accurate, and precise in our setting?

Can we generate a clinically sensible estimate Can we generate a clinically sensible estimate of our patient’s pre-test probability? of our patient’s pre-test probability?

From personal experience, prevalence From personal experience, prevalence statistics, practice databases, or primary statistics, practice databases, or primary studies studies

Are the study patients similar to our own? Are the study patients similar to our own? Is it unlikely that the disease possibilities or Is it unlikely that the disease possibilities or

probabilities have changed since this probabilities have changed since this evidence was gathered? evidence was gathered?

Will the resulting post-test probabilities affect Will the resulting post-test probabilities affect our management and help our patient? our management and help our patient?

• Could it move us across a test-treatment Could it move us across a test-treatment threshold? threshold?

• Would our patient be a willing partner in Would our patient be a willing partner in carrying it out? carrying it out?

• Would the consequences of the test help our Would the consequences of the test help our patient reach his or her goals in all this?patient reach his or her goals in all this?

Questions to answer in Questions to answer in applyingapplying a a valid diagnostic test to an individual valid diagnostic test to an individual

patientpatient

1.1. Does early diagnosis really lead to Does early diagnosis really lead to improved survival, or quality of life, improved survival, or quality of life, or both? or both?

2.2. Are the early diagnosed patients Are the early diagnosed patients willing partners in the treatment willing partners in the treatment strategy? strategy?

3.3. Is the time and energy it will take us Is the time and energy it will take us to confirm the diagnosis and provide to confirm the diagnosis and provide (lifelong) care well spent? (lifelong) care well spent?

4.4. Do the frequency and severity of the Do the frequency and severity of the target disorder warrant this degree target disorder warrant this degree of effort and expenditure?of effort and expenditure?

Guides for deciding whether a screeningscreening or early diagnosticearly diagnostic mmaneuveraneuver does more good than harm:

•Absolute Risk•Risk Difference •Relative Risk•Adjusted Relative Risk•Attributable Risk•Population Attributable Risk•Absolute Risk Reduction (ARR)•Relative Risk Reduction (RRR)•Numbers Needed to Treat (NNT)•Numbers Needed to Harm (NNH)

Ukuran Ukuran Resiko

Apakah A berhubungan dengan B?

•Exposure•Treatment•Program•Process•Characteristic•Behavior

•Effect•Death•Outcome•Cost•Disease

Risk Difference= R.D.Risk Difference= R.D.Perbedaan ResikoPerbedaan Resiko

Risk difference= IRisk difference= IEE - I - ICC

(incidence terpapar) - (incidence (incidence terpapar) - (incidence tidak terpapar)tidak terpapar)

ContohContoh Intervensi : Fosamax; Controls: Intervensi : Fosamax; Controls:

PlaceboPlacebo Outcome: Fraktur KlinisOutcome: Fraktur Klinis IIEE == 11.9 per 100; I11.9 per 100; ICC = 14.7 per 100 = 14.7 per 100 Risk difference = 11.9-14.7 = -2.8 Risk difference = 11.9-14.7 = -2.8

per 100per 100

Relative Risk (RR)Relative Risk (RR)RR = IRR = IEE/I/ICC

(incidence in exposed) / (incidence (incidence in exposed) / (incidence in in

non-exposed)non-exposed) Contoh:Contoh:

Intervensi: Fosamax; Controls: Intervensi: Fosamax; Controls: PlaceboPlacebo

Outcome: Fraktur KlinisOutcome: Fraktur Klinis IIEE == 11.9 per 100; I11.9 per 100; ICC = 14.7 per 100 = 14.7 per 100 RR = 11.9/14.7 = 0.81RR = 11.9/14.7 = 0.81

Interpretasi dari Relative Interpretasi dari Relative RiskRisk

RR = 1RR = 1

RR > 1RR > 1

RR < 1RR < 1

Insiden kelompok terpapar dan Insiden kelompok terpapar dan tidak terpapar(Tidak ada tidak terpapar(Tidak ada Hubungan)Hubungan)

Insiden kelompok terpapar lebih Insiden kelompok terpapar lebih besar dari kelompok tidak besar dari kelompok tidak terpapar.terpapar.

Insiden kelompok terpapar lebih Insiden kelompok terpapar lebih kecil dari kelompok tidak kecil dari kelompok tidak terpapar.(Protektif)terpapar.(Protektif)

Rumus Relatif RiskRumus Relatif Risk

OutcomeYes No Total

ExposureYes a b a + b

No c d c + d

Relative risk = incidence in exposedincidence in nonexposed

Hitunglah Resiko relatif

Heart Disease

Yes No

RegularYes 40 360 400

ExerciseNo 200 1400 1600

RR = I(e) = a/(a+b)I(ne) c/(c+d)

Interpretation:

Penelitian Kasus Kontrol

Hip Fracture(cases)

NoHip Fracture

(controls)

ReceivedHealthPromo

a

Did NotReceiveHealthPromo

c

ReceivedHealthPromo

b

Did NotReceiveHealthPromo

d

Penelitian Kasus Kontrol

Hip Fx(cases)

No Hip Fx(controls)

Promo a b

No Promo c d

Total a + c b + d

Odds Ratio (OR) or Relative Odds (RO) =

Odds that a case was exposed = a dOdds that a control was exposed b c

Hitunglah Odd Ratio

Hip Fx NoHip Fx

Promo 100 200

No Promo 900 800

Odds Ratio = = =

Interpretation:

Hitunglah Odd RatioCHD

Cases Controls

Smokers 120 170

Non-Smokers 80 230

Total 200 400

Odds Ratio =

Interpretation:

Adjusted RiskResiko yang disesuaikan

KegunaanKegunaan

Untuk dapat dibandingkanUntuk dapat dibandingkan

Memperhitungan perbedaan Co-Memperhitungan perbedaan Co-Variate Variate

yang ada yang ada dalam group yang ditelitidalam group yang diteliti

Metoda Penyesuaian/Adjustment

StandarisasiStandarisasiMantel – HaenszelMantel – HaenszelLog-linear modelsLog-linear models

risk modelsrisk models odds modelsodds models rate modelsrate models incidence-time modelsincidence-time models

LatihanMiokard infark Jumlah

Postif Negatif  

Positif 170 80 250

Negatif 80 170 250

  250 250 500

Odd ratio (170x170): (80x80) = 4.52  

Latihan dan Miokard Infark

Measures of exposure effect [95% CI]Risk ratio : 2.13 [1.74, 2.59]Odds ratio : 4.52 [3.10, 6.58]Risk difference : 0.36 [0.28, 0.44]Proportional attributable risk : 0.53 [0.43, 0.61]Population proportional attr. risk : 0.36 [0.27, 0.44]

1. Umur kelompok MI, 80% orang berusia diatas 50 tahun dan hanya 20 % pada kelompok Non MI termasuk kelompok usia > 50 tahun tersebut .

2. Apakah perbedaan usia pada dua kelompok dapat menjelaskan hubungan ini atau sepenuhnya resiko 4.52 kali tersebut hanya dipengaruhi oleh faktor tidak olah raga/latihan dan tidak dipengaruhi oleh umur

3. Harus dibuktikan dulu bahwa umur bukan confounder 4. Bila umur adalah confounder maka dipertanyakan berapa sebenarnya resiko

terjadinya MI yang memang disebabkan oleh faktor tidak latihan/olahraga sebaliknya

5. Umur bukan confounder maka berarti resiko terjadinya MI pada kelompok yang tidak berolahraga memang 4.52 kali dibandingkan dengan yang berolahraga atau dengan kata lain insiden MI pada kelompok berolahraga dibandingkan tidak berolah raga adalah 1 : 4.52 dimana setiap 100 pasien MI kelompok yang berolaharaga maka didalam populasi terdapat 452 kasus MI kelompok individu yang tidak berolah raga.

6. Subjek studi menjadi dua kelompok yaitu usia 6.1. dibawah 50 tahun 6.2. lebih dari 50 tahun 6.3. Dilihat hubungan antara latihan dan kejadian MI pada masing-masing kelompok usia.

Adjusted odd ratio tidak sama dengan Crude Odd RatioUmur adalah Confounding

1. cOR/aOR > 0,15

2. cOR/aOR < 0,87

CONFOUNDER POTENSIAL

Adjusted RRMyocardial Infarction

Yes No Total

Education

High School 100 1700 1800

College 60 1140 1200

Oral Contraception

Never 130 2570 2700

1-4 years 5 105 110

5-9 years 10 120 130

10 + years 15 45 60

Total 160 2840 3000

Myocardial Infarction

Crude RR

Adjusted* RR

95% C.I.

Education

High School 1.11 --

College -- --

Oral Contraception

Never -- --

1-4 years 0.98 1.0 (0.9-1.1)

5-9 years 1.60 1.3 (0.9-1.7)

10 + years 5.20 4.1 (2.1-6.1)

*Adjusted for educational status

Adjusted RR

Absolute Risk Reduction Absolute Risk Reduction (ARR)(ARR)

Absolute Risk Reduction (ARR)Absolute Risk Reduction (ARR) adalah adalah perbedaan angka kejadian antara perbedaan angka kejadian antara kelompok kontrol dan kelompok kelompok kontrol dan kelompok perlakuan(control group (CER) dan perlakuan(control group (CER) dan exposure group (EER): ARR = CER - exposure group (EER): ARR = CER - EER.EER. Perlakuan: FosamaxPerlakuan: Fosamax Controls: PlaceboControls: Placebo Outcome: Fraktur KlinisOutcome: Fraktur Klinis CERCER == 14.7 per 100; EER = 11.9 per 10014.7 per 100; EER = 11.9 per 100 ARR = 14.7-11.9 = 2.8 per 100ARR = 14.7-11.9 = 2.8 per 100

NNTNNT Adalah penderita yang harus Adalah penderita yang harus diobati untuk mengurangi 1 tambahan diobati untuk mengurangi 1 tambahan outcome yang jelek (death, stroke, outcome yang jelek (death, stroke, etc.). etc.).

Perhitungan: NNT = 1/ARR = 1/(2.8%) Perhitungan: NNT = 1/ARR = 1/(2.8%) =35.7 = 36 penderita untuk =35.7 = 36 penderita untuk mengurangi 1 kematian atau efek jelek mengurangi 1 kematian atau efek jelek lainnyalainnya

NNHsNNHs Adalah jumlah penderita yang Adalah jumlah penderita yang harus ditambahkan untuk menimbulkan harus ditambahkan untuk menimbulkan 1 effek buruk (side effect, etc.)1 effek buruk (side effect, etc.)

Number needed to treat= NNTNumber needed to treat= NNT

TERAPI / PENGOBATAN

memilih terapi yang terbaik untuk penderita

1. Menentukan tujuan terapi apakah kuratif, paliatif atau hanya menghilangkan gejala,

2. Memilih terapi yang spesifik apakah memang penderita membutuhkan terapi, apakah terdapat bukti, asal sumber bukti tersebut yang menyatakan bahwa terapi tersebut adalah terapi yang spesifik untuk mencapai tujuan terapi.

3. Menentukan target terapi agar dapat ditentukan kapan menghentikan pengobatan, kapan mengganti dengan obat lain

PERMASALAHAN KLINIS PASIEN

FORMULASI PERTANYAN KLINIS YANG DAPAT DIJAWAB

PENELUSURAN ARTIKEL YANG RELEVANLIBRARY SEARCHINGSOFTWARE

LIST OF ARTIKEL

TELAAH KRITIS ARTIKEL/CRITICAL

APPRAISAL

PEMILIHAN ARTIKEL YANG RELEVAN

KUMPULAN ARTIKEL RELEVAN

APPLYING EVIDENCE/PENERAPAN BUKTI

PICO

Patient/Problem Intervention

Comparison Intervention Outcome

HIPERTENSI DENGAN TD DIASTOLIK 110 mmHg

1.Tujuan terapi : Untuk mencegah kerusakan target organ seperti otak, mata, jantung, ginjal, pembuluh darah besar yang dapat menimbulkan kecacatan ataupun kematian dikemudian hari.

2.Pilihan terapi : Obat anti hipertensi berdasarkan uji klinik tersamar ganda.

3.Target terapi : menurunkan tekanan darah diastolik dibawah 90 mmHg

PENENTUAN ARTIKEL YANG COCOK UNTUK RUJUKAN TERAPI

1. Apakah artikel yang dibaca relevan------- baca Abstraknya

Telaah abstract:1.1. Apakah hasil studi cocok dengan dengan kita butuhkan bila ya

lanjutkan bila tidak stop jangan dibaca. 1.2. Apakah permasalahan yang disajikan sering dijumpai pada

praktek anda sehari hari di RS dan intervensi yang dilakukan laik untuk dilakukan bila ya lanjutkan bila tidak stop

1.3. Apakah informasi yang didapat dari artikel tersebut dapat membawa perubahan pada cara perawatan pasien ditempat anda

` pada saat ini. Bila ya lanjutkan bila tidak stop

BiLA ARTIKEL SUDAH RELEVAN MAKA DAPAT DILANJUTKAN KE TAHAP TELAAH KRITIS SELANJUTNYA

VALIDITAS ARTIKEL YANG DIBACA

1. Apakah subjek penelitian di alokasikan secara random bila ya lanjutkan bilaTidak stop atau dapat dikatakan tidak valid

2. Apakah subjek yang diteliti tidak mempunyai kesamaan dengan dengan Subjek ditempat anda bila ya stop bila tidak lanjutkan (tidak aplikabel)

3. Apakah subjek penelitian secara keseluruhan termasuk didalam kesimpulan Penelitian3.1. Apakah follow up lengkap3.2. Apakah subjek dianalisa sesuai pada random alokasinya Beri penjelasan

4. Apakah jenis penelitian single/double/triple blind5. Apakah jumlah kelompok kontrol dan dan perlakuan sama6. Apakah hasil penelitian bermakna dan bila yang dilakukan negatif trial

apakah power of test cukup besar

Untuk tidak terjebak maka bila akan memakai evidence Based Medicine gunakan Cat Nipper yang secara langsung mengarahkan ke literature yang cocok hanya

tinggal melakukan Telaah Kritis PUSTAKA YANG KONVENSIONAL TIDAK BANYAK MENOLONG ATAU KADANG

KARENA TERPAKSA TIMBUL SALAH ARAH

Resume pertanyaan telaah kritis Terapi

1. Apakah alokasi subyek penelitian ke kelompok terapi atau kontrolbetul-betul secara acak? (Validitas)

2. Apakah semua keluaran (outcome) dilaporkan ? (Applicability)

3. Apakah lokasi studi menyerupai lokasi anda bekerja atau tidak ? (Applicability)

4. Apakah kemaknaan statistik maupun klinis dipertimbangkan atau dilaporkan ? (Validitas dan kegunaan (applicabillity).

5. Apakah tindakan terapi yang dilakukan dapat dilakukan ditempat anda bekerja atau tidak ? (Applicability)

6. Apakah semua subyek penelitian diperhitungkan dalam kesimpulan

(Validitas)

Apakah kemaknaan statistik maupun klinis dipertimbangkan atau dilaporkan ? (Validitas dan kegunaan (applicabillity).

 STATUS PENDERITA

ADVERSE EVENT RATE

PLACEBO ACTIVE Rx

Kerusakan organ sasaran sebelumnya

.22 0,8

Tanpa kerusakan organ sebelumnya .10 .04

Parameter 

Adverse event ratesRelative Risk

Reduction (RRR)

Patients status at entryPlacebo

PActive Rx

A(P – A) = RRR

P

Prior target organ damage .22 .08.22 – 0.8= 64

.22

No prior target .10 0.4.10 – 0.4 = 60 .10

Parameter Adverse event rates Ukuran Resiko

Patients status at entry

PlaceboP

Active RxA

RRRAbsolute Risk

Reduction

Prior target organ damage

.22 .08 

64% 

.22 - .08 = 14

No prior organ damage

.10 0.460%

 .10 - .04 = .06

 

1. Bila didapat RRR 50% menunjukkan pasti bermakna klinis, akan tetapi sering kali juga RRR 25% dianggap sebagi bermakna

klinis.2. Absolute Risk Reduction (ARR) yaitu dengan mengukur dengan

penurunan probabilitas dengan kelompok kontrol (plasebo) dengan kelompok perlakuan (Active Tx )

kausa kausa == etiologi, patogenesis atau etiologi, patogenesis atau mekanismemekanisme

Kausa memandu pendekatan klinik Kausa memandu pendekatan klinik untuk prevensi, diagnosis dan untuk prevensi, diagnosis dan pengobatan.pengobatan.

banyak faktor banyak faktor yang yang menyebabkan menyebabkan kausa dinamakan web of causation kausa dinamakan web of causation (fletcher RH, 1988)(fletcher RH, 1988)

KAUSA

Tidaklah mungkin untuk Tidaklah mungkin untuk membuktikan hubungan kausal membuktikan hubungan kausal SECARA PASTISECARA PASTI

Hubungan kausa dan efek untuk Hubungan kausa dan efek untuk manusia harus ditetapkan pada manusia harus ditetapkan pada manusia yang utuhmanusia yang utuh

peluang (kesalahan acak) peluang (kesalahan acak) bias (kesalahan bias (kesalahan

sistematik)sistematik)

efek kausa efek kausa efek-efek (perancu)efek-efek (perancu)

kausa efek (kausa dan kausa efek (kausa dan efek)efek)

(Hulley SB, 1988)(Hulley SB, 1988)

ASOSIASI SEMU

ASOSIASI MURNI

ASOSIASI

OXIDATIFLDL

KOLESTEROLTINGGI

M.C.I

1.UMUR2.ROKOK3.OVERWEIGHT4.OLAHRAGA5.GENETIK6.STRESS7.HIPERTENSI8.PERILAKU MAKAN

1.COVARIAT

2.CONFOUNDING

ASOSIASISEMU

1.STRATIFIKASI MANTENHAENZEL2.LOGISTIK REGRESSION

ASOSIASIMURNI

ASOSIASI SEMUASOSIASI SEMU

meniadakan asosiasi semu oleh meniadakan asosiasi semu oleh karena karena bias bias ((kesalahan kesalahan sistematiksistematik)) Fase desainFase desain

Tentukan kesesuaian antara subyek, Tentukan kesesuaian antara subyek, prediktor, dan keluaranprediktor, dan keluaran

Fase analisisFase analisisMengumpulkan data tambahan untuk Mengumpulkan data tambahan untuk

mengantisipasi bias potensialmengantisipasi bias potensialMenguji konsistensinya dengan studi Menguji konsistensinya dengan studi

lainnyalainnya

asosiasi murni bukan kausa asosiasi murni bukan kausa efekefek

efek kausaefek kausa Fase desainFase desain

Rencanakan studi longitudinalRencanakan studi longitudinal Dapatkan data urutan riwayat Dapatkan data urutan riwayat

dari variabeldari variabel Fase analisisFase analisis

Pertimbangkan kecocokan Pertimbangkan kecocokan biologisnyabiologisnya

Prognosis adalah suatu prediksi perjalanan penyakit mulai dari awal penyakitnya

Perbedaan antara uji prognostik dengan uji diagnostik uji diagnostik memprediksi adanya suatu penyakit uji prognostik memprediksi keluaran dari suatu penyakit (Hulley SB.1998).

PROGNOSIS

PERBEDAAN PERBEDAAN RESIKO DAN PROGNOSISRESIKO DAN PROGNOSIS

1.1. Resiko memprediksi kejadian-kejadian Resiko memprediksi kejadian-kejadian probabilitas yang rendah, sedangkan probabilitas yang rendah, sedangkan prognosis menggambarkan kejadian yang prognosis menggambarkan kejadian yang relatif sering. (KEJADIAN)relatif sering. (KEJADIAN)

2.2. Untuk resiko dihitung permulaan terjadinya Untuk resiko dihitung permulaan terjadinya sakit. Sedang untuk prognosis dihitung sakit. Sedang untuk prognosis dihitung ragam konsekuensi dari penyakitragam konsekuensi dari penyakit. . (KELUARAN)(KELUARAN)

3.3. Faktor bertambahnya risiko bisa sama atau Faktor bertambahnya risiko bisa sama atau berbeda dengan yang menandai berbeda dengan yang menandai ProgonosisProgonosis(FAKTOR) (FAKTOR)

TanpaPenyakit resiko Prognosis

TimbulPenyakit

Keluaranpenyakit

KematianKecacatan

Kekambuhandll

FaktorResiko

FaktorPrognostis

Di- Bagian Bedah RSMH telah banyak dilakukan tindakan terhadap fraktur tibia dengan memakai IM Nailing akan tetapi pada medical rekord didapatkan beberapa penderita yang harus di-operasi ulang karena tulang tibia yang patah tidak menyatu anda sebagai seorang residen diinstruksikan untuk mengguanakan evidence Based Medicine untuk menalaah masalah ini

P.I.C.O

Progonostik faktor apa yang berhubungan dengan peningkatan resiko re-operasi sesudah tindakan terapi operatif fraktur tibia

FORMULASI PERTANYAN KLINIS YANG DAPAT DIJAWAB

PERMASALAHAN KLINIS PASIEN

Search Article with software/lacak artikel dengan perangkat lunak

Pilih tibial fracture (MeSH) and Shaft

Sudah dipilihkan sebanyak 24 artikel sekaligus oleh Software yangBiasanya dengan pilihan terbaik pada urutan pertama

BhandariM.TornettaP. 3rd, Sprague S, Najibi S.Petrisor b.Griffith.L Predictor of reoperation following operative management of fractures of the tibial shaft

Critical appraisalApplying evidence

PEKERJAAN RUMAH KELOMPOK BAGIAN BEDAH KERJAKAN PERMASALAHAN

REOPERASI SHAFT TIBIAL FRACTUREUNTUK DIPRESENTASIKAN PADA SEMINAR EPIDEMIOLOGI KLINIK DAN EVIDENCEBASED

MEDICINE

DENGAN MELAKUKAN TELAAAH KRITIS ARTIKEL

BhandariM.TornettaP. 3rd, Sprague S, Najibi S.Petrisor b.Griffith.L Predictor of reoperation following operative management of fractures of the tibial shaft

PERMASALAHAAN BOLEH DIRUBAH MINTA PETUNJUK PENGAJARPROGNOSTIC

Angka Kematian/KEJADIAN Batasan (dalam persen)

- Kesintasan hidup lima tahun (five year survival)

Pasien yang hidup selama 5 tahun yang dimulai dari beberapa titik dalam perjalanan penyakitnya.

-Kasus kematian (case fatality) Pasien yang mati karena penyakitnya.

- ResponsPasien yang menunjukkan adanya sesuatu kemajuan sesudah mendapatkan intervensi

- Remisi Pasien yang masuk dalam tahap yang penyakitnya tidak lagi dapat dideteksi

- Kekambuhan Pasien yang kambuh penyakitnya sesudah sesuatu interval bebas penyaakit.

Angka kejadian yang dipakai untuk menggambarkan prognosis

Worksheet for Using an Article About Prognosis

Prevensi : apakah dengan intervensi penyakit dapat dicegah, apakah deteksi dini dan pengobatan dapat memperbaiki perjalanan penyakit.

Kausa : kondisi apa yang menimbulkan penyakit ? apa mekanisme patogenetik