GRADEexample application of

Jan Brożek< brozek@gradepro.org >

My potential conflicts of interest

• GRADE working group• Cochrane Collaboration

problem

Q: what to do about it

gather evidence

what evidence says

how believable is evidence

summarise it

balance good & bad

individual preferences

A: recommendation

problem

evidence

solution

Outlin

e

problem

• What are the phenomena associated with the problem?

• What is frequency of the problem?• What causes the problem?

(aetiology)• Does this person have the problem?

(diagnosis)• What if one gets the problem?

(prognosis)• What can we do about the problem?

(treatment)• … etc.

Questio

ns

Should oral oseltamivir be used for treatment of avian influenza (H5N1) in healthy individuals?

Questio

n

avian flu A (H5N1) patients

oseltamivir

no antiviral

mortality

hospitalization

adverse effects

antimicrobial resistance

resource use

Questio

nP:

I:

C:

O:

evidence

systematic review

cannot DO systematic review

use EXISTING

there is NO existing

do PRAGMATIC search

how believable is evidence

• limitations• inconsistency• indirectness• imprecision• publication bias

• large effect• dose-response• „antagonistic bias”

what is the evidence

• no RCT of oseltamivir for H5N1• 5 RCTs in seasonal influenza – hospitalization: OR 0.22 (0.02–2.16)– pneumonia: OR 0.15 (0.03–0.69)

Evid

ence

solution

• no RCT of oseltamivir for H5N1• 5 RCTs in seasonal influenza – hospitalization: OR 0.22 (0.02–2.16)– pneumonia: OR 0.15 (0.03–0.69)

• 3 published case series• many in vitro and animal studies • no alternative more promising• Cost: ~ €40 per course

Evid

ence

• quality of existing evidence

• balance of desirable and undesirable effects

• values and preferences

• cost (resource utilization)

Strength

Because I like it better that way!

Oseltamivir for Avian Flu

Recommendation In patients with confirmed or strongly suspected infection with avian influenza A (H5N1) virus, clinicians should administer oseltamivir as soon as possible (? recommendation | very low quality evidence)

Schunemann et al. The Lancet ID, 2007

strong ? weak

Oseltamivir for Avian Flu

Recommendation In patients with confirmed or strongly suspected infection with avian influenza A (H5N1) virus, clinicians should administer oseltamivir as soon as possible (strong recommendation | very low quality evidence)

Values and PreferencesThis recommendation places a high value on the prevention of death in an illness with a high case fatality. It places relatively low values on adverse reactions, the development of resistance and costs of treatment.

Schunemann et al. The Lancet ID, 2007

Oseltamivir for Avian Flu

RemarksDespite the lack of controlled treatment data for H5N1, this is a strong recommendation, in part, because there is a lack of known effective alternative pharmacological interventions at this time.

The panel voted on whether this recommendation should be strong or weak and there was one abstention and one dissenting vote.

Schunemann et al. The Lancet ID, 2007

quality of evidence

strength of recommendation

questions

Jan Brożek<brozek@gradepro.org>