EBMDr. Nada AlYousefiApril 25, 2012

Motivation: EBM “Successes”

•Theophylline and asthma▫We were doing the wrong thing

Littenberg, 1988

•Beta blockers and MIs▫We weren’t doing the right thing

Yusuf, 1987

Uses of “EBM”

•Use of empirically-verified treatments in the care of patients

•Incorporation of research results into the process of care

•Ability to critically appraise research results

What is Evidence-Based Medicine?

•“The integration of individual clinical expertise with the best available clinical evidence from systematic research.”

David L Sackett, W Scott Richardson, William Rosenberg, R Brian Haynes Evidence Based Medicine--How to Practice and Teach EBM, 1996

▫Various definitions

About 1/3 of worthwhile

evidence is eventually refuted

or attenuated

About 10% of published evidence

is worth reading

About 1/2 of relevant evidence is

not implemented

5 A’s

Steps of ebm

AppraisedAppraised TopicTopicTopicTopic::A subject of discussion or conversation

AppraiseAppraise::To evaluate, & estimate the quality, amountof validity, results and applicability

CriticalCritical::careful, exact evaluation and judgment

CriticallyCritically

“Best Available Clinical Evidence”•Therapy

▫Double-blind, placebo-controlled, randomized clinical trial

•Diagnosis▫Independent, blind comparison with a

reference standard•Prognosis

▫Representative and well-defined prospective cohort of patients at a similar point in the course of disease

•See Centre for Health Evidence

Levels of Evidences• (I-1) a well done systematic review of 2 or more

RCTs

• (I-2) a RCT

• (II-1) a cohort study

• (II-2) a case-control study

• (II-3) a dramatic uncontrolled experiment

• (III) respected authorities, expert committees, etc..

• (IV) ...someone once told me.... http://www.phru.org/casp/ See also AAFP

“Systematic Research”

•“Meta-analysis”

•“Literature synthesis”

▫From Michael Scriven

Questions

ARIF

Centre for EBM: http://163.1.212.5/docs/focusquest.html

Questions: PICO

Problems• Should a 30-year-old

woman with recurrent uncomplicated lower UTIs be advised to drink cranberry juice to prevent reinfection?

• For a 63 year old woman with Type 2 diabetes, is gabapentin superior to amitriptyline as first-line therapy for painful peripheral neuropathy?

Presentation will cover:• Relavance• PICO• search strategy• search results• the validity of this

evidence• the importance of

this valid evidence• can this valid,

important evidence be applied to your patient

Task•Well formulated question?•Formulate the query•Report back to us on your success•The whole group reports back in a week

Search for the Best Evidence

•Review articles•Community/professional standards•Systematic reviews•Original results

What are the Sources of Good Evidence?

www.welch.jhu.edu

http://ksu.edu.sa/Deanships/library/Pages/Home.aspxhttp://ksu.edu.sa/Deanships/library/Pages/Home.aspx

http://http://saudi.digitallibraryplus.comsaudi.digitallibraryplus.com

National Guideline Clearinghouse

www.guideline.gov

Website

CochraneWebsite

TRIP Database

www.tripdatabase.com(75 resources)…

Website

UpToDate

Website

Getting to PubMed

PubMed Response

PubMed Clinical Query

www4.ncbi.nlm.nih.gov/PubMed/

PubMed, Clinical Query, cont’d

Question

Context

Subject matter

Website

Controlled Vocabulary for Subject Matter

www.ncbi.nlm.nih.gov/pubmedwww.ncbi.nlm.nih.gov/pubmed

•Key concepts!•Auther

Stopwords

MeSH(The Medical Subject Headings )

Exercise

•Use the MeSH Database to build a strategy that will find citations to references discussing the economics of community-acquired pneumonia.

Exercise

•Use the NLM Catalog Journal search page to see if PubMed includes the journal, Molecular Microbiology. If so, retrieve all PubMed citations from this journal.

Exercise

•Use the Clinical Queries to find systematic reviews for accidents caused by sleep deprivation.

Search

•What role does pain have in sleep disorders?

Search

•To search for citations to articles written by Bonnie W. Ramsey about gene therapy for cystic fibrosis

Search

•To search for citations to articles about drosophila in the journal Molecular Biology of the Cell

Exercise

•Find citations to articles about the ethics of liver transplantation. Check Details to see how the terms are mapped. Filter to review articles. Select a few items and add them to the Clipboard. Go to the Clipboard and view the selected items in Abstract format to see the assigned MeSH terms.

Exercise

•Use the MeSH Database to build a strategy that will find citations to articles about schizophrenia resulting from prenatal exposure to influenza. Schizophrenia and influenza should be the major topics of the articles.

line Time

Types of Studies

Case ControlCase Control

Cross Cross SectionalSectional

Clinical TrialClinical Trial

Cohort studyCohort study

`Case SeriesCase Series

CaseReport

Types of Epidemiological Studies•Observational

Case Reports, Case series Cross - Sectional Case- Control Cohort

•Interventional Clinical Trials

Systematic review of RCTsSystematic review of RCTs

RCT

Cohort

Case control

InterventionalInterventional

ObservationaObservationall

validity

What’s A Paper on Therapy?•Clinical Trial (Controlled) Compares

INTERVENTION

with CONTROL

Clinical Trial Compares– INTERVENTION

Drug (New) Structured exercise program (e.g. osteoporosis) Surgical procedure

– CONTROL Placebo, old drug or old intervention Usual regular advise given (osteoporosis) Another surgical procedure / No surgery

Preparation: Randomization, Computer generated list

Eligibility assessment (Inclusion/exclusion) Consent Allocation to study arms (Concealment) Baseline assessment Initiation of intervention (Blind) Follow-up Outcome assessment Data analysis

process of RCTs

Appraise the Evidence• Assess validity? Correctness )likely

to be true(

• What are the results? Clinically

important

• Can we apply the results to our patient? Applicable in and useful for my patients

April 21, 2023

EBM

Jeddah Working

Group

64

VALIDITYRandomization.Concealment. Blindness. Follow up complete.Intention to treat.Similar groups at start.Both groups treated equally.

Randomization Randomisation = similar groups at

baseline Equal (50%) chance to be in either groupHow was it randomized?Was randomization concealed?

- selection- allocation

concealed allocation

Did investigators know to which group the potential subject would be assigned before enrolling them?

Trials with unconcealed allocation consistently overestimate benefit by ~40%

Selection bias

Reduced by: centralised randomisation on-site computer system with group

assignments in a locked file sequentially numbered, sealed, opaque

envelopes

Not: alternation, dates of birth, day of week.

BlindnessWho is Blind?

- Physicians-Nurses-Patients-Data gathering staff- data analyzers.

- Single, double…

Blindness•If patient knows: Placebo effect

Those who are on effective treatment perform better than those who receive Placebo

•If Physician knows: Overestimate Treatment effect (More care, Co-intervention)

Rx

C

Potential Subjects

Intervention starts

Outcome

Follow-up

• Selection bias • Performance bias

BlindnessConcealed Allocation

● duration of study.

● drop out < 20%.

All patients analyzed in the groups to which they were allocated

INTENTION TO TREAT (ITT)

200

100 100

50 70

3050

4040 IMPROVED

80%

OR

40%

57%

OR

40%

Drop out Drop out

intervention

control

Sources of bias in trials

Target population

Allocation

Selection bias

Performance bias

Attrition bias

Detection bias

Intervention Control

group(A) group

(B) Not exposed Exposed

Follow-up Follow-up

Outcomes Outcomes

Two balanced groups:

• Start Balanced: All prognostic factors are equally distributed at the start (Concealed Randomization)

• Run Balanced: All prognostic factors are maintained balanced throughout the study (Blindness and the 3C)

• End Balanced: All prognostic factors are maintained balanced at the end of the study (ITT)

Intervention

Therapy• ARR•RR

•RRR•NNT•CI

Result•Result Experimental Event Rate (EER)

Risk (or chance) of outcome event in experimental group

•Results control event rate (CER) Risk (or chance) of outcome event in

control group.

78

Result

Relative Risk (RR)•A measure of the chance of the event

occurring in the experimental group relative to it occurring in the control group.

•RR = EER / CER

79

•RRR=CER-EER/CER

•A RRR of 25% means that the new treatment reduced the risk of death by 25% relative to that occurring among control patients; the greater the relative risk reduction, the more effective the therapy.

Relative Risk Reduction (RRR ):.

•The absolute difference between the risk of the event in the control and experimental groups.

•ARR = CER – EER

Absolute Risk Reduction (ARR)

•Measure of clinical significance

•How many pat’s have to be treated with intervention in order one patient Would expected to benefit.

• NNT=1/ARR

•Conversely, can do number needed to harm▫uses harmful outcomes, eg death, weight gain

Number needed to treat (NNT)

Magnitude (treatment Magnitude (treatment effect)effect):

•Absolute effects (ARR & NNT)•Relative effects (RR, RRR )

Precision:Precision:oP value.P value.•Confidence interval?

Result Tabulation

Event Event

+ Ve+ VeEventEvent

- Ve- VeTotalTotal

ExperimentExperimental al

aabba+ba+b

ControlControlccddc+dc+d

•EER = Experimental Event Rate (a/a+b)

•CER = Control Event Rate (c/c+d)

BleedinBleedingg

presentpresent

BleedingBleeding

AbsentAbsentTotalTotal

Drug ADrug A 20208080100100Drug BDrug B40406060100100

•EER-A (Risk A) = 20/100 = 20% (0.2)•CER-B (Risk B) = 40/100 = 40% (0.4)

ARR = CER - EER

NNT = 1 / ARR

RR = EER/CER (Risk A/Risk B)

RRR = 1- RR

BleedinBleedingg

presentpresent

BleedingBleeding

AbsentAbsentTotalTotal

Drug ADrug A 20208080100100Drug BDrug B40406060100100

•ARR = CER - EER

NNT = 1 / ARR

•RR = EER/CER

RRR = 1- RR

ARR = CER – EER = 0.4 – 0.2 =

0.2 (20%)

NNT = 1 / ARR = 1/0.2 = 5

RR = EER/CER = 0.2/0.4 =

0.5

RRR = 1- RR = 1- 0.5=

0.5 (50%)

Confidence intervals?•The range within which the likelihood of a true value is expected to be within a given degree of certainty, usually evaluated at 95% CI.

•Precision

Summary•Validity - is the paper

likely to be true

•Importance - size of effect▫NNT ▫Percision

•Applicability - can it work for me/my setting

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