examples of systematic reviews goran poropat. cochrane systematic reviews to make unmanageable...
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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
Clearly stated set of objectives
Explicit, reproducible methodology
Systematic search
Assessment of validity
Systematic presentation
Protocol for a Cochrane review
Idea
Register title
Write protocol
To minimize the potential for bias in the review process
Changes possible
Bezafibrate for primary biliary cirrhosis
Title* Protocol information: Authors* Contact person* Dates What’s new History The protocol: Background* Objectives* Methods: Criteria for selecting studies for this review: Types of studies* Types of participants* Types of interventions* Types of outcome measures*
Search methods for identification of studies* Data collection and analysis* Acknowledgements References: Other references: Additional references Other published versions of this review Tables and figures: Additional tables Figures
Supplementary information: Appendices Feedback: Title Summary Reply Contributors About the article: Contributions of authors Declarations of interest* Sources of support: Internal sources External sources Published notes
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
Bezafibrate for primary biliary cirrhosis
MethodsTypes 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
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
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
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
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
Search results
91 PUBLICATIONS IDENTIFIED
65 PUBLICATIONS ASSESSED
7 PUBLICATIONS INCLUDED
6 TRIALS INCLUDED
26 DUPLICATES
58 PUBLICATIONS EXCLUDED
4 TRIALS (N=82)Bezafibrate vs. no intervention
2 TRIALS (N=69)Bezafibrate vs. UDCA
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)
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
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
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
Other results
Fixed-effect analysis
Random-effect analysis
Significant decrease of ALP, GT, ALT, IgM
No effect on GT, ALT, IgM
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