Wiseman Martin - 20th International Nutrition Congress 2013

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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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  • There were five possible grades the panel could assign the evidence for a specific relationship:
    Convincing
    Probable
    Limited Evidence – Suggestive
    Limited Evidence – No Conclusion
    Substantial Effect on Risk Unlikely
  • Meta-analysis of the association between TP53 status and the risk of death at 2 years. Each study is shown by the name of the first author and the risk ratio with 95% confidence intervals. RR is shown with open circle and 95% CI with continuous line. Summary risk ratio and 95% confidence intervals (according to random effects calculations) are also shown: RR is shown with solid diamonds and 95% CI with continuous line. Data are separated into published and indexed; published but not indexed; and retrieved. For CIs that extend beyond the visible range, arrows have been placed.
  • If results are consistent across species and models, this could indicate they might also apply to humans. Since the primary aim of animal experiments is to inform human experimentation, this would be valuable information.
  • How to manage vast body of evidence-Consider limiting reviews to more recent publications when abundant evidence
    Consider early exclusion of inappropriate models
    Use informatics expert
  • Wiseman Martin - 20th International Nutrition Congress 2013

    1. 1. Continuous Update Project Systematic Reviews of Animal and Human Mechanistic Studies Martin Wiseman Medical and Scientific Adviser WCRF International London UK Visiting Professor of Human Nutrition University of Southampton UK IUNS, Granada, 2013
    2. 2. www.dietandcancerreport.org/CUP www.wcrf.org/ICN201
    3. 3. WCRF/AICR Reports citations
    4. 4. Global variation in cancer incidence Breast Colorectal
    5. 5. Migration data Trends in incidence (Japan) Per 100,000, world population standard
    6. 6. Systematic reviews          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
    7. 7. Inferring causality • • • • • • • • Bradford Hill Strength Consistency Specificity Timing Dose Response Plausibility and coherence Experiment Analogy
    8. 8. 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
    9. 9. GRADING THE EVIDENCE      Convincing Probable Basis for recommendations Limited Evidence – Suggestive Limited Evidence – No Conclusion Substantial Effect on Risk Unlikely
    10. 10. 2007 Second Expert Report    Information from mechanistic studiesnarrative reviews Evidence on mechanisms-predefined requirement for grading criteria Considerations:   reviews not systematic could select a mechanism to explain epidemiological associations
    11. 11. CO M M EN T EARTH SY STEM S P a s t c l i m a t e s g iv e v a lu a b le c lu e s t o f u t u r e w a r m i n g p.5 3 7 H ISTORY OF SCI EN CE D e s c a r t e s ’ lo st le t t e r t r a c k e d u sin g G o o g l e p.5 4 0 OBITUARY W y l i e V a l e a n d a n e lu siv e st r e ss h o r m o n e p.5 4 2 29 MARCH 2012 | VOL 483 | NATURE | 531 S . G S C H M E IS S N E R / S P L AVI AN I N FLUEN ZA S h i f t e x p e r t i s e to trac k m u t at io n s w h ere t h e y e m e r g e p.5 3 4 M a n y l a n d m a r k fi n d in g s i n p r e c l i n ic a l o n c o l o g y r e s e a r c h a r e n o t r e p r o d u c i b le , i n p a r t b e c a u s e o f in a d e q u a t e c e l l l i n e s a n d a n i m a l m o d e l s . R a ise st a n d a r d s fo r p r e c lin ic a l c a n c er r e se a r c h C . G len n B eg ley an d L ee M . E llis p ro p o se h o w m et h o d s, p u b lic at io n s a n d in c e n t iv e s m u st c h a n g e if p a t ie n t s a r e t o b e n e fit .
    12. 12. CO M M EN T 29 MARCH 2012 | VOL 483 | NATURE | 531 EART H SYST EM S P a s t c l i m a t e s g iv e v a lu a b le c lu e s t o f u t u r e w a r m i n g p.5 3 7 HI STORY OF SCI ENCE D e s c a r t e s ’ lo st le t t e r t r a c k e d u sin g G o o g l e p.5 4 0 OB ITUA RY W y l i e V a l e a n d a n elu siv e st r e ss h o r m o n e p.5 4 2 S . G S C H M E IS S N E R / S P L AVI AN IN FLUEN Z A S h i f t e x p e r t i s e to t rac k m u t at io n s w h ere t h e y e m e r g e p.5 3 4 M a n y la n d m a r k fi n d i n g s i n p r e c l in i c a l o n c o l o g y r e s e a r c h a r e n o t r e p r o d u c ib l e , i n p a r t b e c a u s e o f i n a d e q u a t e c e l l l i n e s a n d a n i m a l m o d e l s . R a ise st a n d a r d s fo r p r e c lin ic a l c a n c er r e se a r c h C . G len n B eg ley a n d L ee M . E llis p r o p o se h o w m e t h o d s, p u b lic a t io n s a n d in c e n t iv e s m u st c h a n g e if p a t ie n t s a r e t o b e n e f it . E ffo rts o v er th e p a st d e c a d e to c h a r a c t e r iz e t h e g e n e t ic a lte r a t io n s in h u m a n c a n c e r s h a v e le d to a b e tte r u n d e r s t a n d in g o f m o le c u la r d r iv e r s o f t h is c o m p le x s e t o f d is e a s e s . A lt h o u g h w e in t h e c a n c e r f ie ld h o p e d t h a t th is w o u ld le a d to m o r e e f f e c t iv e d r u g s , h is t o r i c a lly , o u r a b i lit y to t r a n s l a t e c a n c e r r e s e a r c h t o c li n i c a l s u c c e s s h a s b e e n r e m a r k a b ly lo w 1. S a d ly , c lin i c a l tr ia ls in o n c o lo g y h a v e t h e h ig h e s t fa ilu r e r a te c o m p a r e d w it h o t h e r t h e r a p e u tic a r e a s . G iv e n t h e h ig h u n m e t n e e d in o n c o lo g y , it is u n d e r s t a n d a b le t h a t b a r r ie r s to c lin ic a l d e v e lo p m e n t m a y b e lo w e r t h a n f o r o t h e r d is e a s e a r e a s , a n d a la r g e r n u m b e r o f d r u g s w it h s u b o p t i m a l p r e c li n i c a l v a li d a t io n w i ll e n te r o n c o lo g y t r i a ls . H o w e v e r, t h is lo w s u c c e s s r a te is n o t s u s t a in a b le o r a c c e p t a b le , a n d © 2 0 12 M a c m il l a n P u b li s h e r s L i m i t e d . A l l r ig h t s r e s e r v e d in v e s t ig a to r s m u s t r e a s s e s s th e ir a p p r o a c h to tr a n sla tin g d is c o v e r y r e s e a rc h in to g r e a te r c lin ic a l s u c c e s s a n d im p a c t . M a n y fa c to r s a r e r e s p o n s ib le fo r t h e h ig h fa ilu r e r a te , n o tw ith s t a n d in g t h e in h e r e n t ly d iff ic u lt n a tu r e o f t h is d is e a s e . C e r ta in ly, th e lim ita tio n s o f p re c lin ic a l to o ls s u c h a s in a d e q u a te c a n c e r - c e ll- lin e a n d m o u s e m o d e ls 2 m a k e it d if fic u lt fo r e v e n 2 9 M A R C H 2 0 1 2 | V O L 4 8 3 | N A T U R E | 5 3 1 • Reproducibility • Relevance of model • Relevance of exposure • Relevance of dose • Route of administration • Publication bias
    13. 13. 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.
    14. 14. Importance • Systematic reviews • • • • • • 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: • • • • • • Allow objective appraisal of evidence Reduce false-positive & false-negative results Identify sources of bias, improving study quality 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
    15. 15. 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
    16. 16. CUP Mechanisms Project Objectives  Two Phases (18 month project)   Develop draft template protocol to stage where it can be tested using specific exposureoutcome link (Phase 1) Carry out feasibility test of developed template protocol for conducting systematic reviews of mechanistic evidence for specific exposurecancer link (Phase 2)
    17. 17. WCRF International Continuous Update Project Systematic review method for mechanistic evidence        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
    18. 18. Systematic reviews of mechanisms Conditions     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…
    19. 19. 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
    20. 20. Challenges     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
    21. 21. 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 
    22. 22. Thank you! www.dietandcancerreport.org/CUP www.wcrf.org/ICN2013

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