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Cochrane Comparing Multiple Interventions Methods Group Oxford Training event, March 2013 1
Statistical considerations in indirect comparisons and network meta-analysis
Said Business School, Oxford, UK
March 18-19, 2013
Cochrane Comparing Multiple Interventions Methods Group Oxford Training event, March 2013
Handout S1-L
Introduction
Julian Higgins
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Two interventions
Network meta-analysis Many different
intervention
Randomized Controlled trials (RCTs)
Meta-analysis of RCTs
Cohort studies, Case-control studies
A new methodological framework
Other names: Multiple-treatments meta-analysis, Mixed-treatment comparison
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Placebo
Toothpaste
Varnish
Rinse
Gel
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3 6
1 69
31 13
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No treatment
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A network of trials: topical fluoride therapy
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2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Year of Publication
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Yes Yes
Conditions for valid inference about ‘best’ treatment
• High internal validity / low risk of bias
• Low risk of reporting bias
• Clinical diversity not relevant or low (high ‘combinability’)
• Good fit of statistical model
Net
wo
rk
Co
nve
nti
on
al
Yes
Yes Yes
Yes
Yes Yes
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Yes Yes
Conditions for valid inference about ‘best’ treatment
• High internal validity / low risk of bias
• Low risk of reporting bias
• Clinical diversity not relevant or low (high ‘combinability’)
• Good fit of statistical model
Net
wo
rk
Co
nve
nti
on
al
Yes
Yes Yes
Yes
Yes Yes
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Considerations extend across studies making different comparisons
Considerations include possibility of inconsistency (conflict) between different types of evidence
Course objectives
• by the end of the course, participants should be able...
– to understand the principles, steps and statistical methods involved in indirect comparisons and network meta-analyses;
– to understand the biases that can distort indirect comparisons and network meta-analysis, including conflict among different sources of evidence, and ways to address these issues;
– to be aware of current thinking in presenting findings from indirect comparisons and network meta-analyses, including issues related to risk of bias and quality (within Summary of Findings tables); and
– to support Cochrane editorial bases in their support of review authors undertaking indirect comparisons and network meta-analysis.
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Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
Outline of the course: Monday
• Pair-wise meta-analysis
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Outline of the course: Monday
• Pair-wise meta-analysis
• Indirect comparisons
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment ?
13
Outline of the course: Monday
• Pair-wise meta-analysis
• Indirect comparisons
– and mixed comparisons
– ‘loops’ of evidence
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
14
Outline of the course: Monday
• Pair-wise meta-analysis
• Indirect comparisons
– and mixed comparisons
– ‘loops’ of evidence
• Meta-regression
– for indirect comparisons
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
15
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
Outline of the course: Monday
• Pair-wise meta-analysis
• Indirect comparisons
– and mixed comparisons
– ‘loops’ of evidence
• Meta-regression
– for indirect comparisons
– for network meta-analysis
16
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
Outline of the course: Monday
• Pair-wise meta-analysis
• Indirect comparisons
– and mixed comparisons
– ‘loops’ of evidence
• Meta-regression
– for indirect comparisons
– for network meta-analysis
• Small group discussion
• Computer practicals
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Outline of the course: Tuesday
• Problem of multi-arm studies
– Full network meta-analysis
– Multivariate meta-analysis
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
18
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
Outline of the course: Tuesday
• Problem of multi-arm studies
– Full network meta-analysis
– Multivariate meta-analysis
• Inconsistency (conflicting evidence)
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Outline of the course: Tuesday
• Problem of multi-arm studies
– Full network meta-analysis
– Multivariate meta-analysis
• Inconsistency (conflicting evidence)
• Presentation of results
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
20
Outline of the course: Tuesday
• Problem of multi-arm studies
– Full network meta-analysis
– Multivariate meta-analysis
• Inconsistency (conflicting evidence)
• Presentation of results
• Presentations from small-group discussions
• Group discussion of implications for Cochrane Reviews
Placebo
Toothpaste
Varnish
Rinse
Gel
No treatment
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Cochrane Comparing Multiple Interventions Methods Group Oxford Training event, March 2013 22
Statistical considerations in indirect comparisons and network meta-analysis
Said Business School, Oxford, UK
March 18-19, 2013