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Comprehensive Meta Analysis Version 2.

Introduction to the program

C1 Introduction to CMA

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Comprehensive Meta Analysis (Version 2) is a program developed specifically for use in


meta analysis. It includes three modules Data entry, Data Analysis, and High
resolution plots.
The diuretic meta-analysis
Well be working with a meta analysis that assessed the ability of diuretics to reduce the
risk of pre-eclampsia (PE), a potentially fatal event in pregnant women. Patients were
randomly assigned to treatment with a diuretic or to a control, and the researchers
tracked the number in each group that developed PE.
Start the program
There should be an icon on the desktop for Comprehensive Meta Analysis V2.
Start the program
Select Start a blank spreadsheet and click OK
Insert a column for the study name

Click Insert/ Column for/ Study names

Insert a column for the treatment effect


The program allows you to enter the treatment effect in one (or more) of 100 formats.
For example, you could enter the number of events and sample size in each group or
you could enter the odds ratio and confidence limits. Since many formats are available,
you need to tell the program which format you will be using. (The program also allows
you to enter data for different studies in different formats, and well cover that option
later).

Click Insert/ Column for/ Effect size data

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Click Next two times to get to the list shown here

Drill down to

Dichotomous (number of events)


Unmatched groups, prospective data (e.g. controlled trials, cohort studies)
Events and sample size in each group
Click Finish

The program then allows you to name the groups.

Enter Treated and Control for group names


Enter PE and Normal for outcomes
Click OK

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At this point the spreadsheet should look like this:

Enter the data for the first study into the White cells in row 1
Study name: Weseley
Treated Events 14
Treated Total N 131
Control Events 14
Control Total N 136
The screen should look like this:

Enter the rest of the data


The rest of the data for this meta analysis is shown here. You may continue to enter the
data by hand. Or, use the Files menu to open a copy of this file (Diuretic.cma) which
should be located in C:\Program Files\Comprehensive Meta Analysis Version 2 (You
can copy the file to C:\ or some other directory for easy access. Note that you cannot
open the file by clicking on it. Rather, you need to open it from within CMA).

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Run the analysis

Click Run Analysis on the toolbar.

The program will show the analysis screen (above).


For each study the program shows the odds ratio, lower and upper limit, z-value and pvalue. Toward the right is a forest plot where the odds ratio for each study is
represented by a point, and bounded by its confidence interval.
On this plot, an odds ratio of 1.00 represents no treatment effect. For most studies the
odds ratio falls below 1.00, indicating that patients treated with diuretics were less likely
to develop PE. For a few studies the odds ratio falls above 1.00, indicating that patients
treated with diuretics were more likely to develop PE.
The confidence interval bounding each study reflects the precision of the estimate, with
small studies tending to have wide confidence intervals and large studies tending to
have narrow confidence intervals. We are using the 95% confidence interval in this
picture so the study will be statistically significant (p < .05) if and only if the confidence
interval excludes the null value of 1.0.
The bottom line on this plot is marked Fixed and shows the combined effect for the 13
studies, using the fixed effect model. To wit, the odds ratio is 0.67 with 95% confidence
interval of 0.56 to 0.80, z-value of -1.45 and p-value < 0.000.
Create a high-resolution plot

Click High-resolution plot on the toolbar. The program shows this screen

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Optional section
At this point you have a basic sense of the program: How to enter data, how to perform
an analysis, and how to create a high-resolution plot.
If youd like, you can now run through these three basic sections again. This time,
however, well show some of the options that are available.
On the data entry screen you will

View the formulas.


Customize the display
Enter data using more than one format

On the analysis screen you will

Display additional statistics


Select the computational model
Display weights

On the high-resolution plot you will

Modify the symbols used for studies


Modify the width of the plot
Change color schemes
Export the plot to PowerPoint or to Word.

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Data entry optional issues


Return to the data entry screen by clicking the X box at the upper right to close the
high-resolution graph and the analysis module.
Your screen should look like this.

(If you are starting from scratch, use the Files menu and Open the file Diuretic.cma
which should be located in C:\Program Files\Comprehensive Meta Analysis Version 2).
Display the on-screen guide

Click the Tutorial icon at the right-hand side of the toolbar. This is available for
each module in the program.

View the computations

Double-click on any value in the yellow columns

When you entered data into the white columns the program computed the odds ratio and
log odds ratio and displayed these in the yellow columns. To see how a value was
computed, simply double-click on that value.

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Display the risk ratio

Right-click on the yellow columns and then select Customize Display

By default, the program is displaying the odds ratio, but you can modify the display. You
may elect to display the risk ratio, risk difference, or other indices of treatment effect.
You may also elect to display the variance and/or the standard error.

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Entering data in more than one format


In the running example the data for all studies was available in the same format (events
and sample size for each group). What would you do if some studies presented the data
in an alternate format?
In the running example lets assume that the last two studies, Tervilla and Campbell, had
published the odds ratio and confidence interval. We need to insert an additional set of
columns to accommodate this new data format, and we do this exactly as we did for the
initial set of columns.
For the purpose of this exercise delete the last two studies from the dataset so that we
can re-enter them in the new format.

Highlight the last two studies


Click Edit / Delete row

Click Insert/Column for/ Effect size data

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The program opens this dialog box.


Note that the existing format (events and sample size) is shown in blue.

Drill down to the new format

Dichotomous (number of events)


Computed effect sizes
Odds ratio and confidence limits
Click finish

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The screen now looks like this (above)


On the bottom left corner of the screen there are tabs for Cohort 2x2 (Events) and
Odds ratio.
You can switch between these two formats by clicking on these two tabs.
At the moment the new tab (Odds ratio) is selected, and the columns for this format are
visible (Odds ratio, lower limit, upper limit, confidence level).
Enter data for the two studies as follows.
Do not enter anything into the column labeled Data format.
The program populates this column automatically.
Study name
Odds ratio
Lower limit
Upper limit
Confidence level

Tervila
2.971
.586
15.068
0.95

Study name
Odds ratio
Lower limit
Upper limit
Confidence level

Campbell
1.145
0.687
1.908
0.95

The screen should now look like this:

For the first 7 studies we entered data using events and sample size, while for the next 2
we entered data using odds ratios and confidence limits. In either case the program was
able to compute the log odds ratio and standard error (in the yellow columns) which will
be used in the analysis.
Would you like to see all the data at once?

Right-click in the white columns (e.g. the column for odds ratio) and select Show
all data entry formats

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For studies 1-7 there is data in the first set of columns while the next is grayed-out. For
the next two studies the reverse is true.
Return to normal mode

Right-click in the white columns and select Show only current data entry format

Insert columns for additional variables

The first unused column is J


Double click on that column header and program displays a dialog box
Enter a name for the column
Specify that the column will hold a Moderator
Select the type (Categorical, Integer, or Decimal)

In this example we have created a column for Study quality and defined it as a
categorical moderator (a moderator variable is a study characteristic that may modify the
treatment effect estimate).

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Data analysis Optional section


Retrieve the saved file (the one where data for all studies had been entered as events
and sample size).

Click File/Opening screen wizard/Open an existing file


Select Diuretic.cma

Run the analysis

Click Run analysis on the toolbar

The screen looks like this (above).


Display the weight assigned to each study

Click the tool for Show weights

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Note the weight assigned to Landesman in the analysis.

Click the tool again to turn off the weights

Select another index of treatment effect

On the toolbar, select Risk Ratio


Then, select log odds ratio
Then, select odds ratio to return to the default screen

View detail for the statistics

Click Next table on the toolbar

The program displays a table with additional statistics, including stats for heterogeneity.

Click Next table again to return to the prior display

Select the computational model


At the bottom left-hand corner of the screen there are tabs for Fixed, Random and
Both.

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Click Fixed and note the point estimate and confidence interval
Click Random and note the point estimate and confidence interval
Click Both

When Both models is selected there are two yellow lines at the bottom of the plot one
for Fixed effect and one for Random effects. Under random effects the odds ratio has
shifted to the left and the width of the confidence interval has increased.
Display weights for fixed and random effects simultaneously

With Both selected as the computational model, use the toolbar to display the
weights

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Note the impact of Tervila under random effects as compared with fixed effect.
Customize the display
Now, we are going to customize the display, keeping only those columns that we want to
use in the high-resolution display (with high-resolution display it is usually more effective
if we keep the columns to a minimum and emphasize the graphics of the forest plot).

Use the toolbar to turn off the weights


Right-click on the column for odds ratio and select Customize basic stats

Remove the check-marks from z-value and p-value


Click OK
Select Both Models on the tab at the bottom

The screen should now look like this (below):

High-resolution plot (Optional)

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Click High-resolution plot on the toolbar

Your screen should now display a draft of the high-resolution plot (below) which you can
now proceed to modify.

Proportional vs. one-sized symbols


Note that the symbols are proportional in size to each studys weight under the fixed
effect model. For example, compare the weights for Landesman vs. Campbell.
You can elect to use the same size symbol for all studies or to use the proportional
weights as shown here.
Click One size on the toolbar. Note how one size is used for all symbols.
Click Proportional on the toolbar to return to the prior mode.
Fixed effect vs. Random effects
Note: This option is available only if you selected Both Models on the analysis screen.
At the moment, the Models column shows Fixed and the symbol size for each study
is based on the Fixed effect weight.

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Select Proportional on the toolbar


Select Computational options/ Fixed effects on the menu.

Select Computational options/ Random effects on the menu.

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Note how the weights are more balanced than they had been under the fixed effect
model the difference between the smallest and the largest studies is now minimized.
Modify the title
The basic idea of this (and all modules) is that you can right-click on any area of the
screen to display the relevant options.

Right-click on the title Meta Analysis

This opens a toolbar as shown here with three tabs.

Select the Text tab


Enter Impact of Diuretics on PE
Click Apply

Select the Line under header tab


Click the color icon
Select an alternate color for the line

Modify the labels

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Right-click on the label Favours A


Change the labels to read Favours Tx and Favours Pbo
Click Apply

Right-click on the forest plot (the section toward the right)


Select the option for Study and Summary symbols
Select Circle for the studies

Right-click on the forest plot (the section toward the right)


Select the option for Spacing and Forest plot width
Select the tab for Forest plot width
Try modifying the width of the plot

Export to Word

On the Files menu select Export to Word

This concludes the Introduction to CMA.


Additional PDFs are available on request from MichaelB@Meta-Analysis.com
These are free, and show how to use advanced features in the program.

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