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Examples of systematic reviews

Examples of systematic reviews. Goran Poropat. Cochrane systematic reviews. To make unmanageable amounts of information – manageable Identify, appraise and synthesize research-based evidence Present in an accessible format. Cochrane systematic reviews. C learly stated set of objectives

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Examples of systematic reviews

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  1. Examples of systematic reviews Goran Poropat

  2. Cochrane systematic reviews To make unmanageable amounts of information – manageable Identify, appraise and synthesize research-based evidence Present in an accessible format

  3. Cochrane systematic reviews Clearly stated set of objectives Explicit, reproducible methodology Systematic search Assessment of validity Systematic presentation

  4. Protocol for a Cochrane review Idea Register title Write protocol To minimize the potential for bias in the review process Changes possible

  5. Bezafibrate for primary biliary cirrhosis

  6. Bezafibrate for primary biliary cirrhosis

  7. Bezafibrate for primary biliary cirrhosis • Chronic, progressive, inflammatory and autoimmune-mediated liver disease • Survival in symptomatic patients = 10-15 yr. • Bilirubin – indipendent predictor of survival and prognosis • Bezafibrate – inhibition of acetil-CoA carboxylase activity • PPAR - ATP-binding cassette (ABC) B4 transporter • Increased secretion of phosphatidyl-choline

  8. Bezafibrate for primary biliary cirrhosis Methods Types of studies • RCTs assessing bezafibrate in patients with PBC • Irrespective of blinding, language, publication status • Quasi-randomised and observational studies • Exluded for report of benefit • Included for report of harm

  9. Bezafibrate for primary biliary cirrhosis Types of participants • Pts with PBC • Elevated alkaline phophatases • Positive anti-mitochondrial antibody • Compatible liver biopsy Types of interventions – bezafibrate at any dose or regimen vs. placebo or any other drug

  10. Bezafibrate for primary biliary cirrhosis Types of outcome measures

  11. Bezafibrate for primary biliary cirrhosis Search methods of identification of studies • Cochrane Hepato-Biliary Group Controlled Trials Register • The Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library • MEDLINE • EMBASE • Science Citation Index Expanded • LILACS • Chinese Bio-medical Literature Database • Reference lists of identified studies • Pharmaceutical companies • Clinicaltrials.gov • WHO International Clinical Trials Registry Platform

  12. Bezafibrate for primary biliary cirrhosis Data collection and analysis • Two authors independently • Disagreements resolved by discussion Risk of bias assessment • Allocation sequence generation • Allocation concealment • Blinding • Incomplete outcome data • Selective outcome reporting • Other bias

  13. Bezafibrate for primary biliary cirrhosis Statistical analyses • Fixed-effect and random-effect models meta-analyses • Dichotomous outcomes – RR/RD (95% CI) • Continuous outcomes – MD (95% CI) • Dichotomous outcomes – intention-to-treat • Continuous outcomes – case analysis and inclusion of known data • Assesment of heterogeneity (chi-square test) • Trial sequential analysis

  14. Search results 91 PUBLICATIONS IDENTIFIED 26 DUPLICATES 65 PUBLICATIONS ASSESSED 58 PUBLICATIONS EXCLUDED 7 PUBLICATIONS INCLUDED 6 TRIALS INCLUDED 2 TRIALS (N=69) Bezafibrate vs. UDCA 4 TRIALS (N=82) Bezafibrate vs. no intervention

  15. Characteristics of included studies • All trials from Japan • Parallel groups design (5 trials) • Cross-over design (1 trial) • >85% participants were female • Non-advanced PBC (4 trials) • PBC stage not known (2 trials)

  16. Characteristics of included studies • Bezafibrate 400 mg daily orally • Duration of administration of bezafibrate • 6 moths (2 trials) • 12-13 months (4 trials) • UDCA 600 mg daily orally

  17. Risk of bias judgement All six trials are at high risk of bias

  18. Results:Trials assessing bezafibrate vs. no intervention

  19. ALL-CAUSE MORTALITY LIVER-RELATED MORBIDITY

  20. ADVERSE EVENTS PRURITUS

  21. ALKALINE PHOSPHATASES MD-186, 95% CI -249 to-123; I2 = 34%

  22. Trial sequential analysis (ALP) A minimal relevant difference 100 U/L (based on clinical judgement, more modest than the estimated effect seen in the meta-analysis) Standard deviation 200 U/L Risk of type I error 5% Risk of type II error 20% Required information size 216

  23. TSA – ALKALINE PHOSPHATASES

  24. Other results No effect on IgM Bilirubin GT ALT Total cholesterol Tryglicerids

  25. ConclusionBezafibrate vs. no intervention • No significant effect on mortality, liver-related morbidity, adverse events, and pruritus • Quality of life and fatigue could not be assessed • Trial sequential analysis implies evidence for a beneficial effect on serum alkaline phosphatases activity

  26. Results:Trials assessing bezafibrate vs. ursodeoxycholic acid (UDCA)

  27. ALL-CAUSE MORTALITY LIVER-RELATED MORBIDITY

  28. ADVERSE EVENTS ALKALINE PHOSPHATASES

  29. Other results Significant decrease of ALP, GT, ALT, IgM Fixed-effect analysis No effect on GT, ALT, IgM Random-effect analysis

  30. ConclusionBezafibrate vs. UDCA • No significant effect on mortality, liver-related morbidity, adverse events, and pruritus • Quality of life, pruritus, and fatigue could not be assessed • There is no firm evidence of effect on ALP, GT, ALT, and IgM

  31. CONCLUSIONS Treatment ofprimary biliary cirrhosis with bezafibrate can neither be supported nor rejected

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