GRADE-ing typhoid fever vaccination Steve Schofield Force Health Protection Department of National Defence (DND) Canada
Disclosure I have no conflict(s) of interest to declare
Acknowledgements ( Team Typhoid ) A. Henteleff (chair) C. Greenaway S. Schofield P. Plourde J. Geduld M. Abdel-Motagally M. Bryson (CATMAT secretariat) (CATMAT mbrs) 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
Conclusion Never disagree with Dr. Guyatt, i.e. travel-medicine guidelines can be evidence-based
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
CATMAT Typhoid Statement Typhoid as a trial + WG + RQ s Initial draft SOFs + EPs Statement published 2008 1994 Statement 2010 2011 2012 2013 2014 Systematic review GRADE G. Guyatt consult CATMAT approval Draft to CATMAT CATMAT Evidence-based Medicine Statement Needs update EBM course (w/ G. Guyatt) on hold Updated draft 2008 1994/5 Statement 2009 2010 2011 2012 2013 2014 WG + plan Initial draft GRADE
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
Low risk of bias Moderate risk of bias For other risk factors (age, VFR, length of stay, etc) very low quality data
Moderate risk of bias Assessment by outcome (geographic region) Moderate risk of imprecision
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?