3

1. (Introduction) 4 2. (Asking answerable question) 5 3. (Acquiring the evidence) 7 4. (Appraising the evidence) 13

(Etiology / Harm) 13 (Prognosis) 14 (Diagnosis) 15

/ (Therapy / Prevention) 16 (Systematic reviews) 17 (Economic analysis) 18 5. (Applying the evidence) 19 6. (Assessing outcome) 21 7. (Glossary) 23

4

1

(EBM) EBM = (Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients, David L Sackett) EBM (information explosion) EBM (Etiology/Harm) (Diagnosis) (Prognosis) / (Therapy/Prevention) (Health economics) EBM (The 5 As of EBM) 1. A sk question : 2. A cquire evidence : 3. A ppraise evidence : 4. A pply evidence : 5. A ssess outcome :

5

2

EBM (Asking clinical question) P I C O

1. (P roblem or P atient) 2. (I ntervention) 3. (C omparison intervention) 4. (O utcome)

(P)

.....

(I)

........................ estrogen .......

(C)

............... estrogen ........................................

(O)

.....

(Etiology/Harm) (Prognosis) (Diagnostic test) (Therapy or prevention) (Health economics)

6

PICO (asking clinical question)

Domain Patient (P) Intervention (I) Comparison (C)

Outcome (O)

Therapy

acute

M.I.

aspirin

placebo

recurrent M.I.

Prognosis

hemodialysis

hemodialysis

.

life expectancy

Diagnosis

coronary disease

exercise ECHO

exercise EKG

coronary artery disease

Etiology / Harm

hormone

replacement therapy (HRT)

HRT

CA breast

Economic

chronic renal

failure

renal

transplant

hemodialysis

(cost- effective)

7

3

EBM (Acquiring evidence) 1. (key words) (P) (I) (C) (O) domain (etiology, diagnosis, prognosis therapy, prevention, etc.) (cohort studies, case-control studies, randomized controlled trial, systematic review, meta-analysis) 2.

Cochrane Library http://gateway.ovid.co

m website

Bibliographic database (MEDLINE)

www.pubmed.com

CATs (Critically appraised topics)

www.ebem.org/cats/

appraise

appraise

TRIP (Turning Research Into Practice)

www.tripdatabase.com

8

3. internet websites

PUBMED OVID MEDLINE 1. PUBMED National Library of Medicine

www.pubmed.com address web browser (Internet Explorer) 1

1

Click Clinical Queries ( 1) 2

2

9

category ( 2) therapy diagnosis etiology prognosis Enter subject search click Go

2. OVID MEDLINE : PUBMED OVID MEDLINE OVID server . (http://library.ra.mahidol.ac.th) OVID 3

3

14 1 click

select more than one database to search 5

10

click click to begin search 4

4

(Medical subject Heading, MeSH) Enter Keyword or

phrase check box Limit to click PICO prognosis cohort studies, prognosis, survival analysis

11

Ovid Medline Filters for Evidence-based Clinical Queries

Enter Keyword or phrase click

Domain : Therapeutics/Interventions Domain : Diagnosis1 exp research design/ 2 exp clinical trials/ 3 comparative study/ or placebos/ 4 multicenter study.pt. 5 clinical trial$1.pt. 6 random$.ti,ab. 7 (double blind$ or triple blind$3).ti,ab. 8 placebo$.ti,ab. 9 (clinical adj trial$1).ti,ab. 10 exp epidemiologic research design/ 11 (controlled clinical trial or randomized controlled trial).pt. 12 practice guideline.pt. 13 feasibility studies/ 14 clinical protocols/ 15 exp treatment outcome/ 16 or/1-15

1 exp "sensitivity and specificity"/ 2 false negative reactions/ or false positive reactions/ 3 (sensitivity or specificity).ti,ab. 4 (predictive adj value$1).ti,ab. 5 (likelihood adj ratio$1).ti,ab. 6 (false adj (negative$1 or positive$1)).ti,ab. 7 (randomized controlled trial or controlled clinical trial).pt. 8 double blind method/ or single blind method/ 9 practice guideline.pt. 10 consensus development conference$.pt. 11 random$.ti,ab. 12 random allocation/ 13 (single blind$3 or double blind$3 or triple blind$3).ti,ab. 14 or/1-13

12

Domain : Etiology Domain : Prognosis 1 random$.ti,ab. 2 exp epidemiologic studies/ 3 odds ratio/ 4 cohort$.ti,ab. 5 (case$1 adj control$).ti,ab. 6 risk$.ti,ab. 7 (odds adj ratio$1).ti,ab. 8 causa$.ti,ab. 9 (relative$1 adj risk$).ti,ab. 10 predispos$.ti,ab. 11 (randomized controlled trial or controlled clinical trial).pt. 12 exp risk/ 13 practice guideline.pt. 14 case-control studies/ 15 or/1-14

1 exp cohort studies/ 2 prognosis/ 3 exp mortality/ 4 exp morbidity/ 5 (natural adj history).ti,ab. 6 prognos$.ti,ab. 7 course.ti,ab. 8 predict$.ti,ab. 9 exp "outcome assessment (health care)"/ 10 outcomes$1.ti,ab. 11 (inception adj cohort$1).ti,ab. 12 disease progression/ 13 exp survival analysis/ 14 or/1-13

key word Enter Keyword or phrase click

16+17 search strategy save option save username password ()

13

4

(Etiology) (Harm) 1. (valid)

1.1 1.2 1.3 2 1.4 80

1.5

2. (importance) relative risk (R.R.) cohort study odds ratio (O.R.) case-control study (confidence interval or C.I.) 1 () NNH (number needed to harm) 1

NNH = [{PEER (OR 1) } +1] / [PEER (OR 1) x (1 PEER)] [PEER = patients expected event rate ]

14

(Prognosis) 1. (valid)

1.1

1.2

1.3 (adjust)

1.4

1.5 80 1.6 blind

2. (importance)

2.1. (risk of outcome) 3

- - 50 - 2.2 (precision)

(confidence interval)

15

(Diagnosis) 1. (valid)

1.1 (gold or reference standard) 1.2 1.1 blind (/

) 1.3 1.4 (reproducible)

2. (importance) accuracy test 2.1 sensitivity :

2.2 specificity : 2.3 predictive values : 2.4 likelihood ratio (L.R) :

Disease present (gold std) Disease absent (gold std) Test + a b Test - c d Sensitivity = a/(a+c) Specificity = d/(b+d) Positive predictive value = a/(a+b) Negative predictive value = c/(c+d) L.R. for positive test = {a/(a+c)}/{b/(b+d)} L.R. for negative test = {c/(a+c)}/{d/(b+d)} Prevalence (or pre-test probability) = (a+c) / (a+b+c+d)

16

/(Therapy/Prevention) 1. (valid)

1.1 1.2 1.3 (randomized list concealed) 1.4 80 1.5 intention-to-treat (analyze as randomized) 1.6 1.7

2. (importance) 2.1 p-value (

17

(Systematic reviews) 1. (valid)

1.1 1.2 1.3 (validity) 1.4

2. (importance)

2.1 2.2 2.3 (precision) confidence interval

2.4 3. (Applicability) 3.1 3.2 3.3 3.4

18

(Economic analysis) 1. (valid)

1.1 2 1.2 cost-effectiveness, cost-benefit cost-utility 1.3 cost outcome 1.4 sensitivity analysis

2. (importance)

2.1 cost outcome 2.2 cost outcome (subgroup) 2.3 (sensitivity analysis)

3. (Applicability) 3.1 3.2 3.3

19

5

6. 6.

Diagnostic test pre-test probability

Pre-test odds = (pre-test probability) / (1 pre-test probability) Post-test odds = pre-test odds x LR Post-test probability = post-test odds (ost-test odds + 1) Therapy PEER (Patients Expected Event Rate) NNT () = 1 / (PEER x RRR) 3. 4. 5. 6.

20

6

- - - outcome -

David Sacket. Evidence-Based Medicine : How to Practice and Teach EBM ( New York : Churchill Livingstone, 2000) www.cebm.net www.cebm.utoronto.cawww.cochrane.org

21

Glossary of Evidence-based Medicine

Absolute risk reduction (ARR) treatment effects Accuracy (true positive + true negative) / (true positive + true negative + false positive + false negative) Age standardization () Alpha error error Type I Alternative hypothesis hypothesis Analytic study cross-sectional, cohort case-control Anectdotal evidence 1 (case report) Association 2 (statistical association) (causal association) Attributable fraction (exposed, A.R.) exposure (IE - IU ) / IU (RR - 1) / RR IE incidence in the exposed group, IU incidence in the unexposed group, RR = relative risk Attributable fraction (population, P.A.R.) () exposure (IT - IU ) / IU B(RR - 1) / {B(RR-1) + 1} IT incidence in the total population, IU incidence in the unexposed group, RR = relative risk, B = (exposed proportion)

22

Attributable risk (exposure, E) IE - IU excess risk Beta error error Type II Bias (systematic error) (non-systematic or random error) Blinding single-blind double-blind intervention Case-control study (case) (control) (exposure) odds ratio Case series () () Cause ( Hills criteria) -temporality : -strength : -experiment : -consistency : 1 -coherence : -specificity : -dose-response relationship -biologic plausibility : Chi-square test (discrete or categorical variables)

23

Clinical decision analysis intervention 3 (choice) (chance) (values) intervention Clinical epidemiology classical epidemiology Clinical practice guideline (CPG) Clinical significance magnitude of effect Clinical trial interventions interventions Cluster sampling Cohort Cohort study 2 (exposure) 2 Co-intervention intervention intervention Confidence interval (CI) 95 95% CI = 5 - 15 90 99 Confidence limits (CL) confidence interval

24

Confounding 2 3 Confounding variable, confounder ( 3) 2 Contamination control intervention Control group, controls Control event rate (CER) event rate Correlation coefficient 2 continuous 1 +1 1 1 (linear relationship) Correlation (ecological) study Cost-benefit analysis () Cost-effectiveness analysis () () intervention Cost-minimization analysis () (health effect) Cost-utility analysis (utility) quality gain quality-adjusted life year (QALY) 1 Critical appraisal (validity) (application)

25

Crossover study design 2 Cross-sectional study (exposure) (outcome) Cumulative incidence average risk Decision analysis (or clinical decision analysis) Deduction Descriptive epidemiology Differential misclassification misclassification Dose-response relationship outcome exposure Double-blind blinding Dropout Ecological fallacy Ecological survey (aggregated data) (risk factor) (outcome) Effectiveness efficacy Efficacy effectiveness Efficiency

26

Error, type 1 (alpha error) null hypothesis Error, type 2 (beta error) null hypothesis Event rate EER (experimental event rate) CER (control event rate) PEER (patient expected event rate) treatment effects Evidence-based health care (evidence-based medicine) Evidence-based medicine Experimental event rate (EER) event rate Exposure External validity validity False negative False positive Gold standard Hawthorne effect Hierarchy of evidence I: randomized controlled trial 1 study II-1 controlled trial randomization

27

II-2 cohort case-control studies 1 II-3 uncontrolled studies III (case report / series) Historical control () Hypothesis -null hypothesis (H0) -alternative hypothesis (HA) Inception cohort () Indirect standardizeation/adjustment standardization Inference inferential statistic Information bias exposure outcome Informed consent Intention-to-treat analysis Internal validity validity Kappa 2 2 (P0 Pc) / (1 Pc) P0 = observed agreement, Pc = chance agreement Lead-time bias ()

28

Length bias ( ) Likelihood ratio (LR) Positive LR = Sensitivity / (1 Specificity) Negative LR = (1 Sensitiivity ) / Specificity Meta-analysis Misclassifaction

-differential misclassification -non-differential misclassification Negative predictive value (NPV) Null hypothesis hypothesis Number needed to treat (NNT) 1 1 / ARR Observational study intervention Odds p / (1 - p) Odds ratio 2 odds odds of case ( exposure exposure ) odds of control ( exposure exposure )

29

Outbreak epidemic p-vale (probability value) null hypothesis Patient expected event rate (PEER) event rate Power () 1- beta error Type II Positive predictive value (PPV) Post-test odds pre-test odds x likelihood ratio Post-test probability post-test odds / 1 + post-test odds Precision (reliability, repeatability, reproducibility) (valid) Pre-test odds pre-test probability / (1 + pretest probability) Pre-test probability or prevalence (point prevalence) (period prevalence) Publication bias Random error Randomization (or random allocation) () outcome

30

Randomized controlled clinical trial (RCT) randomize Recall bias Relative risk reduction (RRR) treatment effects Research Risk Risk ratio (RR) () () RR = EER / CER Screening Sensitivity a / a + c SnNout sensitivity (Sn) (N) rule out Specificity d / b + d SpPin specificity (Sp) (P) rule in Standardization 2 -direct standardization -indirect standardization Statistical significance p-value 0.05 Survival analysis Systematic error bias Systematic review (critical appraisal)

31

Treatment effects ARR (absolute risk reduction) = EER - CER RRR (relative risk reduction) = (EER - CER) / CER good outcome RRI (relative risk increase) = (EER - CER) / CER bad outcome ABI (absolute benefit increase) = ARR RBI (relative benefit increase) = RRR NNT (number needed to treat) = 1 / ARR good outcome NNH (number needed to harm) = 1 / ARR bad outcome EER = experimental event rate; CER = control event rate Validity ( bias) Validity, study -internal validity -external validity (generalizability)

(EBM) 2

3

1 2Domain : Etiology(Etiology) NNH = [{PEER (OR 1) } +1] / [PEER (OR 1) x (1 PEER)](Prognosis) (Diagnosis)a

/(Therapy/PrevenARR=CEREER; RRR=(CER EER) / CER

(Systematic re (Economic ana