examples of systematic reviews
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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
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
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
Types of outcome measures
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
Risk of bias judgement
All six trials are at high risk of bias
Results:Trials assessing bezafibrate vs. no
intervention
LIVER-RELATED MORBIDITY
ALL-CAUSE MORTALITY
PRURITUS
ADVERSE EVENTS
ALKALINE PHOSPHATASES
MD -186, 95% CI -249 to -123; I2 = 34%
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
TSA – ALKALINE PHOSPHATASES
Other results
IgMBilirubin
GTALT
Total cholesterolTryglicerids
No effect on
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
Results:Trials assessing bezafibrate vs. ursodeoxycholic acid (UDCA)
LIVER-RELATED MORBIDITY
ALL-CAUSE MORTALITY
ALKALINE PHOSPHATASES
ADVERSE EVENTS
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
CONCLUSIONS
Treatment of primary biliary cirrhosis with
bezafibrate can neither be supported nor rejected
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