“grade-ing typhoid fever vaccination
TRANSCRIPT
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Steve Schofield
Force Health Protection
Department of National Defence (DND)
Canada
“GRADE-ing” typhoid fever vaccination
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Disclosure
I have no conflict(s) of interest to declare
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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
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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
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Never disagree with Dr. Guyatt, i.e. travel-medicine guidelines can be
evidence-based
Conclusion
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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
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Objective (mine)
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Outline
• Timeline
• The evidence
– interventions, but emphasis on baseline risk
• The recommendations
– rationale & terminology
• Strengths and Challenges (GRADE)
• Since statement…
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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
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The Evidence (Does typhoid vaccine versus no vaccine decrease the incidence
of typhoid and associated morbidity and mortality among Canadian travellers?)
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2007 version
• “Typhoid fever” and “travel” • 227 studies identified, 147 included • Three trials for each of Vi polysaccharide and Ty21a (three & two for AEs)
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“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
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↑risk for mild AE (+ nausea and
pain)
Absolute risk more relevant (still not
travellers)
Moderate confidence in
EOF…indirectness as no traveller specific data
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Moderate risk of bias
Low risk of bias
For other risk factors (age, VFR, length of stay, etc)
very low quality data
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Moderate risk of imprecision
Assessment by outcome (geographic region)
Moderate risk of bias
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Attack rate/region
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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
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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?
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3 yrs, 2 GRADE recommendations 1.5 yrs, 10 GRADE recommendations
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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
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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
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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
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Is GRADE “worth” it?
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Questions?