1. Development and the Role of Meta- analysis on the Topic of Inflammation Donald S. Likosky, Ph.D.

2. Disclosures No relevant disclosures

3. Goals for Talk What is a Meta-Analysis? Why is Meta-Analysis Important? How to Interpret a Meta-Analysis Relevance to Inflammation

4. Goals for Talk What is a Meta-Analysis? Why is Meta-Analysis Important? How to Interpret a Meta-Analysis Relevance to Inflammation

6. What is a Meta Analysis A systematic review of a topic, based on discrete question Seeks to address the magnitude and precision of an intervention Unit of analysis is a study (usually restricted to published studies) Meta analysis is not just a big randomized trial

7. What is a Meta Analysis Primary measure is the magnitude of effect across studies (not patients) We don’t average values Weight each study by its sample size –1 / (standard error) 2

8. Reflects findings across published studies There may be reasonable concerns about publication bias Assumes studies focused on same patients & study populations (requires in/exclusion criteria) Assumes authors have provided the required data (sometimes need to correspond with authors)

9. Goals for Talk What is a Meta-Analysis? Why is Meta-Analysis Important? How to Interpret a Meta-Analysis Relevance to Inflammation

10. How do you possible compare these studies? Should they get equal weighting? How much variance might there be in their estimates? Number of Patients in Each of 10 Studies

11. Goals for Talk What is a Meta-Analysis? Why is Meta-Analysis Important? How to Interpret a Meta-Analysis Relevance to Inflammation

12. What is a Meta Analysis Primary measure is the magnitude of effect We don’t average values Weight each study by its sample size –1 / (standard error) 2

13. Primary Measure I 2, “I-squared” Measure of degree to which studies are comparable Want homogenous studies (I 2 <25%)

14. Australian Family Physician Vol. 35, No. 8, August 2006

15. Study ID # in Study Mean (SD) in Intervention Arm # in Study Mean (SD) in Control Arm Effect Measure “Weighted Mean Difference” Weights per Study Overall Effect Degree to which Studies Are Similar Overall Significance Line of Difference

16. Australian Family Physician Vol. 35, No. 8, August 2006

17. BMJ 2011; 343: Scatter plot of the estimated treatment effect for each trial vs precision of the estimated effect Mean difference between treatments in BP for each trial is plotted vs. the reciprocal of the standard error of the estimated treatment effect Funnel Plot for Publication Bias

18. Goals for Talk What is a Meta-Analysis? Why is Meta-Analysis Important? How to Interpret a Meta-Analysis Relevance to Inflammation

20. Of 8 studies on C3a Time Points# Studies Contributing Data Pre-operative8 5-30min on CPB3 45-60min on CPB5 end of CPB5 5-15 after Protamine4 POD 12

21. Pre-operative

22. 5-30min on CPB

23. End of CPB

24. POD 1

25. Conclusions Meta-Analyses have a role in evaluating body of literature They require thoughtful care in their design and interpretation May have a useful role in –Evaluating effects of coated circuits on the inflammatory response, –In improving the design and conduct of future studies