Download - “GRADE-ing typhoid fever vaccination
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?