Comprehensive Meta Analysis Version 2.0

Introduction to the program

C1 – Introduction to CMA — Page 1 —

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 We’ll 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 we’ll cover that option later).

• Click Insert/ Column for/ Effect size data

C1 – Introduction to CMA — Page 2 —

• 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

C1 – Introduction to CMA — Page 3 —

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).

C1 – Introduction to CMA — Page 4 —

C1 – Introduction to CMA — Page 5 —

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 p-value. 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

C1 – Introduction to CMA — Page 6 —

C1 – Introduction to CMA — Page 7 —

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 you’d like, you can now run through these three basic sections again. This time, however, we’ll 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.

C1 – Introduction to CMA — Page 8 —

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.

C1 – Introduction to CMA — Page 9 —

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.

C1 – Introduction to CMA — Page 10 —

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 let’s 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

C1 – Introduction to CMA — Page 11 —

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

C1 – Introduction to CMA — Page 12 —

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 Tervila Odds ratio 2.971 Lower limit .586 Upper limit 15.068 Confidence level 0.95 Study name Campbell Odds ratio 1.145 Lower limit 0.687 Upper limit 1.908 Confidence level 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”

C1 – Introduction to CMA — Page 13 —

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).

C1 – Introduction to CMA — Page 14 —

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”

C1 – Introduction to CMA — Page 15 —

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”.

C1 – Introduction to CMA — Page 16 —

• 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

C1 – Introduction to CMA — Page 17 —

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)

C1 – Introduction to CMA — Page 18 —

• 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 study’s 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.

C1 – Introduction to CMA — Page 19 —

Select “Proportional” on the toolbar Select “Computational options/ Fixed effects” on the menu.

Select “Computational options/ Random effects” on the menu.

C1 – Introduction to CMA — Page 20 —

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

C1 – Introduction to CMA — Page 21 —

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

C1 – Introduction to CMA — Page 22 —