1. Network Meta-analyses a novel way for synthetic reviews. 黃道民

2. Traditional Clinical Trials. Randomized controlled trial Y: outcome X: randomized and placebo controlled High level of evidence if adequately powered.

3. Meta-analysis Combine the information from “similar” trials into a formal summary. Especially when clinical trials are conflicting

4. Example:

5. m

6. In some cases, we would like to know: What do we think about the relative benefits of the treatments before knowing the results from this trial? What information can be gained from the results of this trial? the relative benefits of the treatments?

7. Network Meta-analysis Mixed treatment comparison 利用 “ 貝氏定理 ( 條件機率 )” 為橋，比較各種 治療的強弱。

8. By this mean, we can Which method is the better Which diagnostic methods are better (sensitive or specific) Comparisons between treatments

9. CONTRAST INDUCED ACUTE KIDNEY INJURY (CI-AKI)

10. CI-AKI 3 rd leading cause of hospital acquired AKI (~10%) Adverse outcomes of CI-AKI – Prolonged hospital stay – Long term adverse effect – Cost. Circulation 105: 2259-2264, 2002 Am J Kidney Dis 39: 930-936, 2002.

11. Many options for prevention of CI-AKI N-acetylcysteine Sodium bicarbonate Felodopam Statin Furosemide

12. Ann Intern Med. 2008 Feb 19;148(4):284-94

13. The good: N-acetylcysteine; the bad: furosemide Ann Intern Med. 2008 Feb 19;148(4):284-94

14. But questions remains… ACT trial 2011 (the biggest trial to date) – Neutral effect of NAC in CI-AKI prevention How about high dose? What is the most effective strategy?

15. Aim of current study To compare the efficacy of medical prevention for CI-AKI

16. Methods Conventional meta-analysis Network meta-analysis

17. Search strategy Pubmed before 2011/11/13 Age > 18 y/o underwent non-ionized contrast injection 17

18. Search strategy 18

19. Statistics Conventional meta-analysis. – Random effect model – Software: STATA 11.0 SE. Network meta-analsis – Winbugs for multiple treatment comparison

20. RESULTS

21. PubMed till 2011.12.31 Treatment Arms (8) Citations 80 Age (15) CKD (26) Contrast Study (20) Diretics (4) Dose Study (4) Hydrationa Scheme (16) Incomplete (1) Ionic Contrast (11) Not Human Study (13) Not RCT (87) Other Medications (23) Endpoint Other Than CAN (285) Seconary Analyses (3) Transplantation (8)

22. Identification of Treatment arms. Treatment Arm Placebo Low Dose IV ACT (>1000mg/single dose) High Dose IV ACT (>1000mg/single dose) Low Dose Oral ACT (>1000mg/single dose) High Dose Oral ACT (>1000mg/single dose) Statin NaHCO3 Theophyllin Felodopam

23. Results: to be presented on word doc.

24. Conventional Meta-analysis Low IV ACT vs. placebo OR = 0.58 (0.36 – 0.98) I 2 = 64%

25. Conventional Meta-analysis High IV ACT vs. placebo OR = 0.42 (95%CI: 0.23-0.77) I 2 = 53%

26. Conventional Meta-analysis Low oral ACT vs. placebo OR = 0.77 (95%CI: 0.57 – 1.02) I 2 = 40%

27. Conventional Meta-analysis High oral ACT vs. placebo OR = 0.67 (95%CI: 0.3 – 1.49) I 2 = 18%

28. Conventional Meta-analysis Statin vs. placebo OR = 0.55 (95%CI: 0.3 – 0.95) I 2 = 0.9%

29. Conventional Meta-analysis NaHCO3 vs. placebo OR = 0.5 (95%CI: 0.3 1– 0.80) I 2 = 58%

30. Conventional Meta-analysis Theophylline vs. placebo OR = 1.07 (95%CI: 0.43 – 1.82) I 2 = 59%

31. Conventional Meta-analysis Felodopam vs. placebo OR = 1.11 (95%CI: 0.61– 2.00) I 2 = 43.8%

32. Network Approach

33. Summary of Effects. OR( 95% CrI )Rank PlaceboReferent8 ACT IV Low0.54(0.25-1.15)5 ACT IV high0.40(0.18-0.87)*1 ACT Oral Low0.72(0.51-1.02)6 ACT Oral high0.45(0.19-1.07)2 Statin0.50(0.18-1.31)4 NaHCO30.46(0.28-0.73)*3 Theophyllin0.96(0.39-2.37)7 Felodopam1.06(0.41-2.70)9

34. Conclusion For 8 arms of methods to prevent CI-AKI, – High dose IV ACT – High dose oral ACT – Statin – NaHCO3 Were superior to placebo in meta-analyses Among treatments, – High Dose IV ACT and NaHCO3 were significantly superior to other treatments.

35. Network meta-analyses A well established method for systemic review. Lancet. 2012 Mar 22. [Epub ahead of print]

36. THANKS FOR YOUR ATTENTION.