appraising an article on therapy2013 (1)

7/29/2019 Appraising an Article on Therapy2013 (1)

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Appraising an article on therapy

Madeleine Grace M. Sosa, MDFPPS,FPNA,FCNSP,MSCE

Full professor DLSHSI College ofMedicine


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General objective

To apply the various rules of evidence in

deciding if the results of an article on

treatment is VALID


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Specific Objectives

To discuss the rationale of each of the users

guides pertaining to the validity of claims oneffectiveness

To recognize the strengths and weaknesses ofRCTs as compared to other non-experimentalstudy designs

To define and differentiate the concepts ofvalidity and precision, as pertain to the resultsof clinical trials

To differentiate between dichotomous ,

continuos and other scales of treatment


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Specific Objectives

To recognize the differences between various

measures of treatment effect including

absolute risk reduction, relative risk , relative

risk reduction and number needed to treat

To differentiate the concepts of noise and

bias, as they pertain to clinical trials

To differentiate between a point estimate and

interval estimate of a treatment effect


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APPRAISAL TIPS

Evaluating Directness

Appraising Validity

Interpreting Results Assessing Applicability

Individualizing the Results


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Evaluating directness

Does the study provide a direct enough

answer to your clinical question in terms of

P: patient population with a certain disease

E/I: the exposure( or treatment) to be

administered

C: Comparison group

O: the outcome( or condition ) that the treatmentare intended to prevent or promote

M: Methodology


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P - Who is the patient or what problem isbeing addressed?

I - What is the intervention or exposure?

C What is the comparison group?

O - What is the outcome or endpoint?

Architecture of a focused question: a

4-part review question

+ study designRichardson et al. The well-built clinical question: a key to evidence-based decisions. ACP Journal Club 1995;A-12

Counsell C. Formulating questions and locating primary studies for inclusion in systematic reviews. Ann Intern Med 1997;127:380-7.


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Formulation of a therapy question

Is Zinc effective in treating cold?

In children with common cold, is oral Zinc effective in reducing the duration ofsymptoms, as compared to placebo?

Intervention Outcome

InterventionPatient/problem

Outcome Comparison + RCTs


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Compare the clinical Question with the

Research questionClinical Question Research Question

P

E/I

C

O

M

When will there be a mismatch in P?

What will happen if there is a mismatch in E?

When will there be a discrepancy in O?


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Appraising validity

Were patients randomly assigned to

treatment groups?

Was allocation concealed?

Were baseline characteristics similar at the

start of the trial?

Were patients blinded to the treatmentassignment?


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Appraising validity

Were caregivers blinded to treatment

assignment?

Were study personnel blinded to the

treatment assignment?

Were all patients analyzed under the groups

to which they were originally randomized?

Was follow-up rate adequate?


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BLINDING

Issues in the assessment of outcome status

Use the same methods of ascertainment for

treatment and control groups

Single Double Triple

Subject

Observer X

Analyst X X


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Appraising validity

RandomizationAllocation

ConcealmentBlinding


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Appraising validity.... Methods


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Interpreting results

How large was the effect of the

treatment?

How precise was the estimate of thetreatment effect?


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How large is the effect of treatment?

Compare the outcomes in the treatment and

control groups

Outcomes:

Continuous variable e.g. change in weight,

change in quality of life scale, change in BP

Dichotomous variable e.g. dead or alive,

hospitalized or not


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Measurement of estimates

Dichotomous variable

RR, RRR, ARR

Continuous variableMean difference


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Absolute risk reduction (ARR)

ARR= risk change

ARR: usually in percent

>0%: Treatment is beneficial

=0%:Treatment has no effect


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Example: express your change in weight, if it went down from 80kg (

Wc) to 60kg(Wt)

Absolute weight reduction: weight change=

20kg

I lost 20kg ( 2% of my risk)

RR: new weight/original weight= 60/80=0.75

My risk is now 0.75( I now weigh 75% of what I

used to weigh)

Relative weight reduction: 20/80= 25%

I lost 25% of my risk( I lost 25% of my weight)


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Relative risk (RR)

RR= new risk/ original risk

RR= Rt/Rc

RR: usually in decimal

1.0: treatment is harmful


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Wc) to 60kg(Wt)

Absolute weight reduction: weight change=20kg

I lost 20kg ( 2% of my risk) RR: new weight/original weight= 60/80=0.75

My risk is now 0.75( I now weigh 75% of what Iused to weigh)




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Relative risk reduction (RRR)

RRR= risk change/original risk

RRR= Rc-Rt / Rc

RRR: usually in percent

>0%: Treatment is beneficial

=0%:Treatment has no effect


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Wc) to 60kg(Wt)

Absolute weight reduction: weight change=

20kg

I lost 20kg ( 2% of my risk)

RR: new weight/original weight= 60/80=0.75

My risk is now 0.75( I now weigh 75% of what I

used to weigh)




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Old drug: Ethoxusimide

Treated = 53%

Failure= 47% (Rc)

New drug: Lamotrigine Treated= 29%

Failure= 71%(Rt)

ARR= .47-.71= - .24

RR= .71/.47= 1.5

RR > 1.0

RRR= -.24/.47= -.51% -51%

RRR< 0

****Freedom from Failure : Treated


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Old drug: Ethoxusimide

Treated= 53%

Failure= 47% (Rc)

New Drug : ValproicAcid

Treated: 58%

Failure= 42% (Rt)

ARR= .47 - .42= .05

RR= .42/.47 = 0.89

**RR< 1.0RRR= .05/.47= .106=

10.6%

**RRR >0%

****Freedom from Failure : Treated


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The primary outcome was freedom from treatment

failure after 16 weeks of therapy

Absolute risk reduction: Rc- Rt

risk change(____ of my risk)

RR: Rt/Rc

My risk is now _____( The risk is now ____ of the

previous risk )

Relative weight reduction :Rc-Rt/RC

I lost ____of my risk


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HOW PRECISE WAS THE ESTIMATE OF

THE TREATMENT EFFECT?

Interval estimates

Estimated at 95% CI- 95% sure that the true

effect of the treatment lies within this range RRR 75% ( 95%CI: 52%, 90%)


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CI: confidence interval

When both ends of the CI are on the side of

the benefit, the treatment is definitely

beneficial

When both ends of the CI are on the side of

the harm , the treatment is definitely harmful


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CI: confidence interval

When one end reflects important benefit and

the other end reflects harm, then the study is

inconclusive

When one end reflects a small unimportant

benefit and the other end reflects a small

unimportant harm, then for all intents and

purposes the two treatments being comparedare equal.


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Confidence Interval = 95%

RR= Rt/Rc

RR: usually in decimal

1.0: treatment isharmful

Ex. RR= 0.89 CI= .05- .91

CI = .05-1.23beneficial 1.0 Harmful


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Which is the best CI???

RR=1.0


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Relative risk (rr)

RR= new risk/ original

risk

RR= Rt/Rc

RR: usually in decimal 1.0: treatment is

harmful

A. RR=2.3( 95%CI:1.5, 3.1)

B. RR=0.98(95%CI:0.95,

1.02)

C. RR=0.63 (95%CI:0.53,0.73)

D. RR=0.98(

95%CI:0.50,1.50)


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Assessing applicability

Are there biologic issues that may affect

applicability of treatment?

Are there socio-economic issues affecting

applicability of treatment?


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Individualizing the results

Are the likely treatment benefits worth the potentialharm and costs?

Compute for NNT ( number needed to treat)

NNT=100/ARR ARR= .05

NNT = 100/.05= 2000

you need to treat 2000 patients with seizuresto treat 1 absence epilepsy

NNT x cost of treatment


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Even if a treatment is beneficial, it may have

adverse effects or it may be too expensive

Estimate NNT X cost of treatment (and

duration if relevant)>> overall cost to prevent

the event


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EBM Steps

Learning

Opportunities

Formulating

Questions

Searching for

Evidence

Critical

Appraisal

Integrating

Evidence withClinical scenario

Bringing

Change toPractice

Ward Round +++ (+) + +++ +

Journal Club + ++ +++ + +

Clinical Teaching

And Assessment++ (+) ++ +++ +

Outpatients

Clinic+++ (+) ++ +++ +

Formal Clinical

Meeting+++ (+) + ++ +

Audit ++ ++ ++ + +++


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Clinical

problem

Experience

and expertise

DecisionmakingAuthoritative

practice

Clinical tools to teach various steps of EBM in different clinical settings


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Acquire

(and appraise)evidence

Integrate

evidence

into practice

Appraise

evidence

Managing

bringing change

in practice

Ward rounds,

Clinics

Journal club

Morbidity/mortality

meetingAudit

Clinical

problem

Ask answerable

questions

Apply evidence

in decision

making

Clinical tools to teach various steps of EBM in different clinical settings


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EBM practice requires:

Asking

Acquiring

Appraising

Applying

Assessing

appraising an article on therapy2013 (1)

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