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Meta-Analysis and Systematic Reviews (As12) : Course: PG Diploma/ MSC Epidemiology
Meta-Analysis and Systematic Reviews (As12) : Course: PG Diploma/ MSC Epidemiology
reviews (AS12)
EPM304 Advanced Statistical Methods in Epidemiology
This document contains a copy of the study material located within the computer
assisted learning (CAL) session.
If you have any questions regarding this document or your course, please contact
DLsupport via DLsupport@lshtm.ac.uk.
Important note: this document does not replace the CAL material found on your
module CDROM. When studying this session, please ensure you work through the
CDROM material first. This document can then be used for revision purposes to
refer back to specific sessions.
These study materials have been prepared by the London School of Hygiene & Tropical Medicine as part of
the PG Diploma/MSc Epidemiology distance learning course. This material is not licensed either for resale
or further copying.
London School of Hygiene & Tropical Medicine September 2013 v1.0
This session should take you between 1.5 and 2 hours to complete.
AS01
SM02
Weseley
Preeclampsia
/total in
treated
patients
14 / 131
Preeclampsia
/total in
control
patients
14 / 136
Odds ratio
(95% CI)
1.04 (0.48
2.28)
Flowers
21 / 385
17 / 134
Menzies
14 / 57
24 / 48
Fallis
6 / 38
18 / 40
Cuadros
12 / 1011
35 / 760
Landesman
138 / 1370
175 / 1336
Kraus
15 / 506
20 / 524
Tervila
6 / 108
2 / 103
Campbell
65 / 153
40 / 102
Total
291 / 3759
345 / 3183
0.40 (0.20
0.78)
0.33 (0.14
0.74)
0.23 (0.08
0.67)
0.25 (0.13
0.48)
0.74 (0.59
0.94)
0.77 (0.39
1.52)
2.97 (0.59
15.1)
1.15 (0.69
1.91)
0.69 (0.59
0.81)
The 2nd column shows the number of events in treated patients. The 3rd column
show the number of events in untreated (control) patients.
wi
=
1
vi
i , the summary
W ii
i-1
F =
W i
i-1
Where F (for 'fixed') denotes the assumption that the effect of diuretic is the same in
each study.
Interaction: Tabs: Step 3:
To calculate confidence intervals and do hypothesis tests on the summary estimate
you need the variance of the summary estimate. This is calculated as
1
u
W i
i-1
Pooled
Estima
te
0.672
95% confidence
interval
Lower
Upper
0.564
0.800
Asymptotic
z value
4.455
Pvalue
< 0.001
No. of
studies
9
Interaction: Tabs: 1:
For each study, the box area is proportional to the weight for the study, this is to
stop attention being drawn to extreme estimates. What do you notice about the
confidence interval for the studies with larger boxes?
Interaction: Button: clouds picture (pop up box appears):
The confidence interval for studies with a larger box are narrower, i.e. more precise.
Interaction: Tabs: 2:
The diamond and broken vertical line represent the overall summary estimate. The
confidence interval is given by the width of the diamond.
Interaction: Tabs: 3:
The unbroken vertical line is the null value, i.e. odds ratio of 1 = no effect.
Interaction: Tabs: 4:
Notice that the x-axis for the odds ratio is on a log scale. This is to obtain symmetry
in the plot.
Q=
W i(i - F)
i-1
This is large if the average distance between the individual study effects and the
summary effect is large.
This statistic is referred to the distribution,
if statistically significant then there is evidence against the null hypothesis of a
common effect for all studies.
if not statistically significant, there is no evidence for a heterogenous effect across
trials. ie we would conclude that there is a common effect (homogeneity) across
trials.
You do not have to do this calculation by hand statistics packages that perform
meta-analysis will include a test for heterogeneity
W *ii
i-1
R =
W *i
i-1
Pooled
estima
te
95% confidence
interval
Lower
Upper
Asymptotic
z value
Pvalue
No. of
studies
Random
0.596
0.400
0.889
2.537
0.011
How does the estimate from the random-effects method compare to that from the
fixed-effects method?
Interaction: Button: clouds picture (pop up box appears and text appears on top
RHS)
The random-effects summary estimate is somewhat smaller than the fixed-effects
estimate, but the confidence interval is much wider. This means that it overlaps
more with the individual trial estimates.
Fixed-effects summary estimate
ORF = 0.67 (0.56 to 0.80)
Random-effects summary estimate
ORR = 0.60 (0.40 to 0.89)
Interaction: Button: Swap (table at bottom LHS changes to the following):
Fixed effects meta-analysis (exponential form)
Metho
d
Fixed
Pooled
estima
te
0.672
95% confidence
interval
Lower
Upper
0.564
0.800
Asymptotic
z value
4.455
Pvalue
< 0.001
No. of
studies
9
Pooled
estima
te
95% confidence
interval
Lower
Upper
Asymptotic
z value
No.of
studies
Pvalue
Random
0.596
0.400
0.889
2.537
0.011
9
Test for heterogeneity: Q = 27.265 on 8 degrees of freedom (P
= 0.001)
6.27
Random
weights
2.57
Flowers
8.49
2.88
Menzies
5.62
2.45
Fallis
3.35
1.89
Cuadros
8.75
2.91
68.34
4.09
Kraus
8.29
2.85
Tervila
1.46
1.09
14.73
3.36
Landesman
Campbell
Fixed weights
Estimate
(95% CI)
1.04
(0.48,2.28)
0.40
(0.20,0.78)
0.33
(0.14,0.74)
0.23
(0.08,0.67)
0.25
(0.13,0.48)
0.74
(0.59,0.94)
0.77
(0.39,1.52)
2.97
(0.59,15.10)
1.14
(0.69,1.91)
In recent decades there has been a massive increase in the number of research
studies carried out. Over 2 million articles are published in the biomedical literature
each year.
A summary of the research evidence for any particular area is a difficult task.
In order to collate all the necessary information, collaboration with the investigators
of the primary studies is necessary.
Interaction: Tabs: 4:
Systematic reviews are retrospective, and can be affected by the same bias that
affects other retrospective studies. A good systematic review should therefore be
based on good review methodology.
Interaction: Tabs: 5:
For many reasons, review methods can vary. The review methods employed should
be described for all systematic reviews.
Interaction: tabs: 6:
Some randomised trials, case-control studies and cohort studies may be
unsatisfactory. This does not mean they should simply be excluded from a review.
They should be critically appraised, empirically studied, and the analysis improved.
Overviews of observational studies require a great deal of methodological
development.
Section 8: Summary
The main points of this session will appear below as you click through the step card
opposite. Click on any of the list entries below to go back to that page.
Why use meta-analysis?
Individual studies are often too small to obtain a precise estimate of effect.
The objective of meta-analysis is to combine evidence from several studies.
Common use in research
Systematic reviews and meta-analysis (the quantitative analysis of such reviews) are
now accepted as an important part of medical research. While the analytical methods
are relatively simple, there is still controversy over appropriate methods of analysis.
Increasing importance
Systematic reviews are substantial undertakings, and those conducting such reviews
need to be aware of the potential biases that may affect their conclusions. However,
the explosion in medical research information and the availability of reviews on-line
mean that summaries of research findings are likely to be of increasing importance
to the practice of medicine.
Fixed-effects versus random-effects
If it is correct to assume that the only reason for variation in the study estimates is
due to sampling error, then you can apply the fixed-effects method in a metaanalysis.
If the study effects vary randomly about the population average, the random-effects
method should be applied. The variation in study effects can be assessed using a test
for heterogeneity.
Helping the decision process
Meta-analysis cannot tell a researcher what to do, but it can help with the decisionmaking process.