1. Conflicts of interest Major role in development of GRADE
Ongoing major involvement in GRADE activities – co-Chair of GRADE working group

2. The GRADE approach to clinical practice guidelines
GRADE background
structured question
certainty of evidence
strength of recommendations

3. Which grading system to use?
20+ years – grading recommendations a good idea
many systems available
Australian National and MRC
Oxford Center for Evidence-based Medicine
Scottish Intercollegiate Guidelines (SIGN)
US Preventative Services Task Force
American professional organizations
AHA/ACC, ACCP, AAP, Endocrine society, etc....
cause of confusion, dismay

4. A common international grading system?
GRADE (Grades of recommendation, assessment, development and evaluation)
international group
Australian NMRC, SIGN, USPSTF, WHO, NICE, Oxford CEBM, CDC, CC
~ 35 meetings over last 15 years

5. 80+ Organizations
2005
2006
2007
2008
2009
2010
2011 5 5

6. Structured question Population: Canadian travelers
Intervention: typhoid vaccine
Comparator: no vaccine
Outcomes
Death
Typhoid and associated morbidity
Adverse effects

7. What are we grading? Two components Certainty in body of evidence
Quality, confidence
high, moderate, low, very low
RCTs start high, observational start low
Strength of recommendation
strong and weak

8. Certainty assessment criteria

9. Impact of Typhoid Vaccine - effectivenes
4 Randomized trials
 Risk of bias
Concealement, blinding, LFUP
No serious risk of bias
Precision (efficacy)
Confidence intervals
3 yr incidence: RR 0.51 (0.42 to 0.62)

10. Impact of Typhoid Vaccine - effectiveness
Consistency
All approximately 0.5
Publicatation bias
Not detected
Directness
No study included travellers
Extrapolation from typhoid endemic countries
Rate down for indirectness

11. Need estimates of risk

13. Strength of Recommendation
strong recommendation
benefits clearly outweigh risks/hassle/cost
risk/hassle/cost clearly outweighs benefit
what can downgrade strength?
low quality evidence
close balance between up and downsides

14. Significance of strong vs weak
variability in patient preference
strong, almost all same choice (> 90%)
weak, choice varies appreciably
interaction with patient
strong, just inform patient
weak, ensure choice reflects values
use of decision aid
strong, don’t bother
weak, use the aid
quality of care criterion
strong, consider
weak, don’t consider

16. Values and preferences
No data on the values and preferences of travellers regarding the use of typhoid vaccine were found. The recommendations were made under the belief that the majority of Canadian travellers would consider the decrease in typhoid risk worth the cost and inconvenience of the vaccine if the absolute risk of risk of typhoid was one in 10,000 but not if the risk was less than this. Among destinations for which data are available, travel to South Asia was the only region where risk exceeded this threshold.

17. Recommendations

18. Conclusions
Clinicians and patients need clear, evidence-based recommendations
Requires systematic review of available evidence
GRADE provides structure
Increasingly accepted as definitive system
Recommendations require absolute estimates of benefit and harm and value and preference judgment for tradeoffs
Travel recommendations can be evidence-based