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The 20th International Congress of Nutrition (ICN) hosted by the International Union of Nutritional Science (IUNS) took place on the 15th-20th September 2013, Granada, Spain. WCRF International held a 2-hour symposium on the Continuous Update Project (CUP) entitled ‘Food, Nutrition, Physical Activity and Cancer – Keeping the Evidence Current: WCRF/AICR Continuous Update Project (CUP).’ It included four presentations exploring the latest updates from the CUP.
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Martin Wiseman
Medical and Scientific AdviserWCRF InternationalLondonUK
Visiting Professor of Human NutritionUniversity of SouthamptonUK
IUNS, Granada, 2013
Continuous Update Project -Systematic Reviews of Animal and Human Mechanistic Studies
WCRF/AICR Reports citations
Global variation in cancer incidence
Breast
Colorectal
Per 100,000, world population standard
Migration data Trends in incidence (Japan)
Expert international Task Force for method Nine centres - USA, UK, NL, Italy SLR centre coordinator Test of reproducibility Standardised search, analysis and display Epidemiology and mechanisms Quality assessment Peer review - protocol, report Defined expertise required
Nutrition, epidemiology, systematic review, cancer biology, statistics
Systematic reviews
• Strength• Consistency• Specificity• Timing• Dose Response• Plausibility and coherence• Experiment• Analogy
Bradford Hill
Inferring causality
GRADING CRITERIA
Predefined requirements for:
–Number and types of studies–Quality of exposure and outcome assessment–Heterogeneity within and between study types–Exclusion of chance, bias or confounding–Biological gradient–Evidence of mechanisms–Size of effect
Convincing Probable
Limited Evidence – Suggestive Limited Evidence – No Conclusion
Substantial Effect on Risk Unlikely
Basis for recommendations
GRADING THE EVIDENCE
2007 Second Expert Report
Information from mechanistic studies-narrative reviews
Evidence on mechanisms-predefined requirement for grading criteria
Considerations: reviews not systematic could select a mechanism to explain
epidemiological associations
29 MARCH 2012 | VOL 483 | NATURE | 531
29 MARCH 2012 | VOL 483 | NATURE | 531
• Reproducibility• Relevance of model• Relevance of exposure• Relevance of dose• Route of administration
• Publication bias
Meta-analysis of the association between TP53 status and the risk of death at 2 years
Kyzas P A et al. JNCI J Natl Cancer Inst 2005;97:1043-1055
© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org.
• Systematic reviews • Allow objective appraisal of evidence • Reduce false-positive & false-negative results• Identify sources of bias, improving study quality
• Extensive mechanistic data from animals & cell lines linking diet & cancer
• Rigorous methods for conducting & reporting SRs of mechanistic studies are lacking
• This project should increase the value of mechanistic data:
• Enable more rigorous systematic reviews • Increased precision of estimated effects • Identify gaps in the research evidence• Reduce selective citation of mechanistic evidence• Inform generalisability to humans (e.g. heterogeneity across species &
models)• A potential tool in the translation of basic sciences into
policy & practice
Importance
Mechanisms Protocol Development Group
• Stephen Hursting (chair)
• Andrew Dannenberg
• Johanna Lampe
• Henry Thompson
• Steven Clinton
• Nikki Ford - associate member
Task: develop guidelines on how review of mechanisms could be approached
CUP Mechanisms Project Objectives
Two Phases (18 month project)
Develop draft template protocol to stage where it can be tested using specific exposure-outcome link (Phase 1)
Carry out feasibility test of developed template protocol for conducting systematic reviews of mechanistic evidence for specific exposure-cancer link (Phase 2)
University of Bristol Multidisciplinary team (informatics, statistics,
epidemiology, systematic reviews, cancer biology, pathology, nutrition)
Search terms/inclusion-exclusion criteria How to manage vast number of papers What information to be extracted How to analyse/display results Identify criteria for grading the evidence
WCRF International Continuous Update Project Systematic review method for mechanistic evidence
Reviews to be systematic and peer reviewed
Reviews conducted by exposure Feasibility test of final draft protocol by
external group, including peer review Molecular, cellular, physiological…
Systematic reviews of mechanismsConditions
Overall approach Four workshops with experts within group at
University of Bristol, UK
Regular meetings between workshops refine the protocol carry out searches investigate quality criteria determine inclusion/exclusion criteria consider methods to investigate publication bias consider methods to report/display results
External reference groups CUP Panel Mechanisms PDG
Developing a one size fits all template Finding the relevant studies
Determining study quality
Determining the strength of evidence for different study types
Determining the relevance to humans
Publication bias
Collating and synthesising the evidence Displaying the results
Challenges
Potential Impact Recommendations based on most robust
science
Beyond CUP New methodology-mainstream approach
to review mechanistic studies Inform direction of future research in area
of diet/PA/body fatness and cancer
Thank you!
www.dietandcancerreport.org/CUP
www.wcrf.org/ICN2013
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