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![PubMed translation of query into search terms
PICO Element Search terms for PubMed
P Acute necrotizing pancreatitis “acute necrotizing pancreatitis” [MeSH]
I Prophylactic antibiotics “antibiotic prophylaxis” [MeSH term]
C Placebo
No treatment
“placebo” [MeSH term]
O
Infection
Necrosis
Mortality
“infection” [MeSH term]
“necrosis” [MeSH term]
“mortality” [MeSH term]
* MeSH: Medical Subject Headings in PubMed](https://image.slidesharecdn.com/metaanalysis-140711115800-phpapp01/75/Meta-analysis-7-2048.jpg)
Uploaded byVishal Ramteke
Meta analysis
This document provides an overview of how to conduct a systematic review and meta-analysis. It describes the key steps: (1) asking a focused clinical question using PICO, (2) acquiring relevant studies through database searches, (3) appraising the quality of included studies, (4) analyzing the data using statistical methods to obtain an overall treatment effect size, and (5) reporting results typically in a forest plot. Meta-analyses provide increased statistical power over individual studies but are not without limitations such as potential bias that must be considered when interpreting results.
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Meta analysis
- 1. Critical appraisal ofa systematic review and meta-analysis
- 2. Hierarchy of evidencein quantitative studies McGovern D, Summerskill W, Valori R, Levi M. Key topics in EBM. BIOS Scientific Publishers, 1st Edition, Oxford, 2001.
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- 5. Key components ofyour clinical question PICO Prophylactic antibiotics in pancreatic necrosis Patient SevereAP with CT-proven necrosis I Intervention Prophylactic antibiotic C Comparaison Placebo or no treatment O Outcome Infected pancreatic necrosis – Mortality P
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- 7. PubMed translation ofquery into search terms PICO Element Search terms for PubMed P Acute necrotizing pancreatitis “acute necrotizing pancreatitis” [MeSH] I Prophylactic antibiotics “antibiotic prophylaxis” [MeSH term] C Placebo No treatment “placebo” [MeSH term] O Infection Necrosis Mortality “infection” [MeSH term] “necrosis” [MeSH term] “mortality” [MeSH term] * MeSH: Medical Subject Headings in PubMed
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- 11. Steps of EBM Appraise
- 12. Systematic review &meta-analysis Systematic reviews (SR) Meta-analyses (MA) MA may, or may not, include a SR Egger M et all. Systematic reviews in health care: Meta-analysis in context. BMJ Publishing Group, London, 2nd edition, 2001.
- 13. Definition of meta-analysis “Statisticalanalysis that combines or integrates the results of several independent clinical trials considered by the analyst to be combinable” Proceedings of biopharmaceutical section ofAmerican statistical association. 1988 ; 2 : 28 – 33.
- 14. Rationale for ameta-analysis By combining the samples of individual studies, the overall sample size is increased, thereby improving the statistical power of the analysis as well as precision of estimates of treatment effects
- 15. Steps of meta-analysis Researchersshould write in advance a detailed protocol Formulation of the problem to be addressed Data collection Data recording Data analysis Reporting the results (Forest plot)
- 16. Formulation ofthe addressed problem PICO Study design: RCTs Patient SevereAPwith CT-proven necrosis I Intervention Prophylactic antibiotics C Comparaison Placebo or no treatment O Outcome Infected pancreatic necrosis -Mortality P
- 17. Formulation ofthe addressed problem Specify inclusion & exclusion criteria • Controlled trials • Randomization of patients • Intention to treat principle (ITT) • Preferably blinded • Outcome assessment: p – RR – OR – CIs – NNT Guyatt G, et al. User’s guide to the medical literature. Essentials of evidence based clinical practice. Mc Graw Hill, 2nd ed, 2008.
- 18. Basic structure ofa RCT / Parallel trial PetrieA, Sabin C. Medical statistics at a glance. Blackwell Publishing, 2nd edition, 2005. Most frequently used design
- 19. Data collection Prophylacticantibiotics in pancreatic necrosis • Electronic databases – MEDLINE – EMBAS – CCTR – Cochrane Library – Science Citation Index • Hand search – References from published trials – Major conference abstracts CCTR: Cochrane Controlled Trials Register Bai Y et al.Am J Gastroenterol 2008 ; 103 : 104 – 110.
- 20. Studies included inmeta-analysis All studies conducted All studies published Studies reviewed Gray literature
- 21. Data recording •2 independent observers extract the data • Quality of the studies may be rated with specially designed checklist or scales • Blinding observers to names of authors, institutions, names of journals, funding & acknowledgments
- 22. Antibiotic prophylactic inpancreatic necrosis Flow diagram Bai Y et al.Am J Gastroenterol 2008 ; 103 : 104 – 110.
- 23. Data analysis 2stage statistical process of MA • Treatment effect for each study p value (p) Relative Risk (RR) or Odds Ratio (OR) Confidence Intervals (CIs) Number Needed to Treat (NNT) • Overall treatment effect Calculated as weighted average of individual statistics Statistical power of MAis often very high
- 24. • p >0.05 Statistically insignificant • p < 0.05 Statistically significant Probability value (p value) Statistically significant Clinically significant Doesn't mean
- 25. Risk & Odds RiskOdds a a + b RR: risk patients/risk controls Risk = a b Odds = OR: odds patients/odds controls
- 26. Interpretation of RR& OR OR or RR should be accompanied by CI RR or OR > 1 Increased likelihood of outcome in treatment group RR or OR < 1 Decreased likelihood of outcome in treatment group RR or OR = 1 No difference of outcome between tt & control group
- 27. Confidence intervals Value 95% CI are commonly used 90 or 99% CI are sometimes used Width of CI Indicates precision of the estimate Wider the interval, less the precision CI includes 1 No statistically significant difference CI doesn’t include 1 Statistically significant difference
- 28. Statistical significance &CI (a) Statistically significant , low precision (b) Statistically significant, high precision (c) Not statistically significant, low precision (d) Not statistically significant, high precision Glasziou P et al. Evidence based practice workbook. Blackwell, 2nd edition, 2007.
- 29. Number Needed toTreat (NNT) • Relative risk (RR) Risk in treatment group / risk in control group • Absolute risk reduction (ARR) Risk in control group – risk in treatment group • NNT (expressed in clinically relevant way) 1 /ARR
- 30. Reporting theresults The typical graph for displaying results of a meta-analysis is called a ‘‘forest plot’’
- 31. Antibiotic prophylaxis &pancreatic necrosis Forest plot Bai Y et al.Am J Gastroenterol 2008 ; 103 : 104 – 110.
- 32. Antibiotic prophylaxis &pancreatic necrosis Horizontal line Scale measuring the treatment effect Bai Y et al.Am J Gastroenterol 2008 ; 103 : 104 – 110.
- 33. Antibiotic prophylaxis &pancreatic necrosis Vertical line or line of no effect Treatment & control groups have the same effect Bai Y et al.Am J Gastroenterol 2008 ; 103 : 104 – 110.
- 34. Antibiotic prophylaxis &pancreatic necrosis Point estimate & CIs for each study Bai Y et al.Am J Gastroenterol 2008 ; 103 : 104 – 110.
- 35. Point estimate (RRor OR) & CI Gallin JI, Ognibene FP. Principles & practice of clinical research. APress, 2nd ed, 2005.
- 36. Antibiotic prophylaxis &pancreatic necrosis Diamond Bai Y et al.Am J Gastroenterol 2008 ; 103 : 104 – 110.
- 37. The diamond Perera R,Heneghan C, Badenoch D. Statistics Toolkit. Blackwell Publishing Ltd, Oxford, 1st edition, 2008. Shows combined point estimate (OR or RR) & CI for the meta-analysis
- 38. Diamond in meta-analysis Diamondon Left of the line of no effect Less episodes of outcome of interest in treatment group Diamond on Right of the line of no effect MoRe episodes of outcome in treatment group Diamond touches the line of no effect No statistically significant difference between groups Diamond does not touch the line of no effect Difference between two groups statistically significant
- 39. Antibiotic prophylactic effecton mortality The diamond Bai Y et al.Am J Gastroenterol 2008 ; 103 : 104 – 110.
- 40. Meta-analytic analyses areprone to bias & need to be interpreted with caution Bias: difference between study results & truth
- 41. Bias in meta-analysis(1) Publication bias: Studies never published Studies with no beneficial effect of treatment Studies sponsored by pharmaceutical industry Studies from a single centre versus multiple centers Language bias: Positive findings published in a international journal Negative findings published in a local journal Database bias: Journals not indexed in major databases
- 42. Language bias 40 pairsof trials published by the same author Controlled trials with statistically significant results was higher among reports published in English Egger M et all. Lancet 1997 ; 350 : 326 – 9.
- 43. Funnel plots Bias detectedby simple graphical test • Plot for each trial RR or OR on x axis Sample size on y axis • Absence of bias Plot should resemble inverted funnel or Christmas tree • Presence of bias Plot shows asymmetrical & skewed shape
- 44. Ideal funnel plot Thesmaller the trial, the larger the distribution of results Cleophas TJ et all. Statistics applied to clinical trials. Springer, The Netherlands , 3rd edition, 2006.
- 45. Cut Christmas tree CleophasTJ et all. Statistics applied to clinical trials. Springer, The Netherlands , 3rd edition, 2006. Negative trials not published (missing) Suspicion of considerable publication bias in this MA
- 46. Appraising & applyingmeta-analysis Heneghan C, Badenoch D. EBM toolkit. BMJ Books, London, 1st edition 2002.
- 47. Questions for appraisingMA Clearly focused question Focused question Identification of all relevant studies Good search Inclusion the right type of study Yes (RCTs) Assessment quality of all studies Yes but no blinding Reasonable to combine study results Yes (good X2 & I2) CriticalAppraisal Skills Programme. Appraisal Tools. Oxford, UK. http://www.phru.nhs.uk/casp/appraisa.htm (accessed 10 Dec 2004).
- 48. Questions for appraisingMA – 2 Precision of the results No (wide 95% CI) Result presentation & main result RR (95% CI) No difference CriticalAppraisal Skills Programme. Appraisal Tools. Oxford, UK. http://www.phru.nhs.uk/casp/appraisa.htm (accessed 10 Dec 2004). Results applied to local population Mainly alcoholic Change practice as result of MA No? All important outcomes considered Antibiotic SE?
- 49. Steps of EBM Assess
- 50. Improving quality ofreports RCTs Diagnostic accuracy study Meta-analysis *Altman DG et al. Ann Intern Med 2001 ; 134 : 663 - 94. ** Moher D et al. Lancet 1999 ; 354 : 1896 - 900. *** Bossuyt PM et all. BMJ 2003; 326 : 41 – 44. Consolidated Standards of Reporting Trials CONSORT* STARD** Standards for Reporting of DiagnosticAccuracy Quality of Reporting of Meta-analyses QUOROM**
- 51. “Doing a meta-analysisis easy, doing one well is hard” Ingram Olkin
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