Steve Schofield

Force Health Protection

Department of National Defence (DND)

Canada

“GRADE-ing” typhoid fever vaccination

Disclosure

I have no conflict(s) of interest to declare

Acknowledgements (“Team Typhoid”)

• A. Henteleff (chair)

• C. Greenaway

• S. Schofield

• P. Plourde

(CATMAT mbrs)

• J. Geduld

• M. Abdel-Motagally

• M. Bryson

(CATMAT secretariat)

CATMAT = Committee to Advise on Tropical Medicine and Travel

CATMAT (Committee to Advise on Tropical Medicine and Travel)

Current Membership (voting, liaison, ex-officio): ...a bunch of really smart people (McCarthy, Libman, Boggild, Greenaway, Brophy, Crockett, Teitelbaum, Bui, Vaughan, McDonald, Tepper, Marion, Audcent, Pernica, Gershman [US CDC]) + an entomologist (Schofield)

P011.09: Canada's Recommendations for Travel Health: The Role of the Committee to Advise on Tropical Medicine and Travel

Never disagree with Dr. Guyatt, i.e. travel-medicine guidelines can be

evidence-based

Conclusion

Objective (ISTM)

Describe the GRADE process applied in a travel medicine framework including its strengths and weaknesses. Review the process of using GRADE to produce the

CATMAT guideline on international travellers and typhoid vaccine, and outline the challenges encountered

Objective (mine)

Outline

• Timeline

• The evidence

– interventions, but emphasis on baseline risk

• The recommendations

– rationale & terminology

• Strengths and Challenges (GRADE)

• Since statement…

2009 2010 2011 2012 2013 2014 2008

1994/5 Statement

Needs update

WG + plan

EBM “course” (w/ G. Guyatt)

Initial draft

“on hold”

GRADE

Updated draft

CATMAT Evidence-based Medicine Statement

2010 2011 2012 2013 2014 2008

1994 Statement

Typhoid as a trial + WG + RQ’s

Systematic review

GRADE CATMAT approval

CATMAT Typhoid Statement

Initial draft

SOFs + EPs

Statement published

G. Guyatt consult Draft to

CATMAT

The Evidence (Does typhoid vaccine versus no vaccine decrease the incidence

of typhoid and associated morbidity and mortality among Canadian travellers?)

2007 version

• “Typhoid fever” and “travel” • 227 studies identified, 147 included • Three trials for each of Vi polysaccharide and Ty21a (three & two for AEs)

“Middling” efficacy…consistent

across groups

Absolute risk not relevant (i.e. not the

baseline risk for travellers)

Moderate confidence in

EOF…indirectness as no traveller specific data

↑risk for mild AE (+ nausea and

pain)

Absolute risk more relevant (still not

travellers)

Moderate confidence in

EOF…indirectness as no traveller specific data

Moderate risk of bias

Low risk of bias

For other risk factors (age, VFR, length of stay, etc)

very low quality data

Moderate risk of imprecision

Assessment by outcome (geographic region)

Moderate risk of bias

Attack rate/region

Why only for South Asia?

• Threshold-based (risk > 1/10,000 travellers) • Only South Asia meets this threshold; other regions ca. 5 X or more less “risky” • “Only” does not mean “only” (is a conditional recommendation)

For other risk factors (age, VFR, length of stay, etc.) very low quality evidence

Why a conditional recommendation? • Evidence for and magnitude of vaccine efficacy = strong recommendation?

The “buts” • Paucity of evidence for values and preferences of travellers (likely variable) • Very low confidence in estimates of effect for risk factors other than destination • Absolute benefit is “pretty low” • The “buts” apply to many other travel medicine interventions?

3 yrs, 2 GRADE recommendations 1.5 yrs, 10 GRADE recommendations

Summary - Strengths • GRADE can be used to develop TM

recommendations

• Transparent and rigorous (for interventions)

• ↑ used by guideline developers (e.g., WHO, ACIP, Cochrane)

• Overt consideration of values and preferences

• Outcome-based, separation of quality assessment and recommendations

• Flexible...one groups yes can be another’s no

Summary – Challenges (1) • Resource/knowledge intensive:

– If resources constrain, then careful selection of EBM questions

– ↓ to # guidelines/time period?

• Learning curve including learning not to GRADE everything

• Establishing and “GRADEing” baseline risk

Summary – Challenges (2) • Scant evidence for:

– Itinerary & traveller-specific risk factors

– Patient values and preferences

• Given above, translating evidence into recommendations, e.g., what are appropriate thresholds for action (or non-action)

• Not black and white for end-user

• Can make people mad

Is GRADE “worth” it?

Questions?