1 Metan metan varlist [if] [in] [weight] [, measure_and_model_options options_for_continuous_data output_options forest_plot_options ] where measure_and_model_options may be or rr rd fixed random fixedi peto cornfield chi2 breslow nointeger cc(#) wgt(weightvar) second(model or estimates and description) first(estimates and description) and where options_for_continuous_data may be cohen hedges glass nostandard fixed random and where output_options may be by(byvar) nosubgroup sgweight log eform efficacy ilevel(#) olevel(#) sortby(varlist) label(namevar yearvar) nokeep notable nograph nosecsub and where forest_plot_options may be legend(string) xlabel(#,...) xtick(#,...) boxsca(#) nobox nooverall nowt nostats group1(string) group2(string) effect(string) force ...with further forest_plot_options in the version 9 update lcols(varlist) rcols(varlist) astext(#) double nohet summaryonly rfdist rflevel(#) null(#) nulloff favours(string # string) firststats(string) secondstats(string) boxopt() diamopt() pointopt() ciopt() olineopt() classic nowarning graph_options labbe varlist [if exp] [in range] [weight] [, nowt percent or(#) rr(#) rd(#) null logit wgt(weightvar) symbol(symbolstyle) nolegend id(idvar) textsize(#) clockvar(clockvar) gap(#) graph_options Description These routines provide facilities to conduct meta-analyses of data from more than one study and to graph the results. Either binary (event) or continuous data from two groups may be combined using the metan command. Additionally, intervention effect estimates with corresponding standard errors or confidence intervals may be meta-analyzed. Several meta-analytic methods are available, and the results may be displayed graphically in a forest plot. A test of whether the summary effect 2 measure is equal to the null is given, as well as a test for heterogeneity, i.e., whether the true effect in all studies is the same. Heterogeneity is also quantified using the I-squared measure (Higgins et al. 2003). metan (the main meta-analysis routine) requires either two, three, four, or six variables to be declared. When four variables are specified these correspond to the number of events and nonevents in the experimental group followed by those of the control group, and analysis of binary data is performed on the 2 x 2 table. With six variables, the data are assumed continuous and to be the sample size, mean, and standard deviation (SD) of the experimental group followed by those of the control group. If three variables are specified, these are assumed to be the effect estimate and its lower and upper confidence interval, and it is suggested that these are log transformed for odds ratios or risk ratios and the eform option used. If two variables are specified, these are assumed to be the effect estimate and standard error; again, it is recommended that odds ratios or risk ratios are log transformed. labbe draws a L'Abbe plot for event data (proportion of successes in the two groups). This is an alternative to the graph produced by metan8. Note that the metan command now requires Stata 9 and has been updated with several new options. Changes are mainly to graphics options that are discussed in the section Further options in the v9 update for metan: Forest plot, or otherwise marked v9 update. The previous version is still available under the name metan7. Remarks on funnel (discontinued) The metafunnel command has more options for funnel plots and version 8 graphics; as such funnel has been removed. See metafunnel (if installed) Options for metan +----------------------------------+ ----+ Specifying the measure and model +--------------------------------These options apply to binary data. rr pools risk ratios (the default). or pools odds ratios. rd pools risk differences. fixed specifies a fixed effect model using the method of Mantel and 3 Haenszel (the default). fixedi specifies a fixed effect model using the inverse variance method. peto specifies that Peto's method is used to pool odds ratios. random specifies a random effects model using the method of DerSimonian & Laird, with the estimate of heterogeneity being taken from the from the Mantel-Haenszel model. randomi specifies a random effects model using the method of DerSimonian and Laird, with the estimate of heterogeneity being taken from the inverse-variance fixed-effect model. cornfield computes confidence intervals for odds ratios by method of Cornfield, rather than the (default) Woolf method. chi2 displays chi-squared statistic (instead of z) for the test of significance of the pooled effect size. This is available only for odds ratios pooled using Peto or Mantel-Haenszel methods. breslow produces Breslow-Day test for homogeneity of ORs. cc(#) defines a fixed continuity correction to add in the case where a study contains a zero cell. By default, metan8 adds 0.5 to each cell of a trial where a zero is encountered when using inverse variance, Der-Simonian and Laird, or Mantel-Haenszel weighting to enable finite variance estimators to be derived. However, the cc() option allows the use of other constants (including none). See also the nointeger option. nointeger allows the cell counts to be nonintegers. This may be useful when a variable continuity correction is sought for studies containing zero cells, but also may be used in other circumstances, such as where a cluster-randomised trial is to be incorporated and the "effective sample size" is less than the total number of observations. wgt(weightvar) specifies alternative weighting for any data type. The effect size is to be computed by assigning a weight of weightvar to the studies. When RRs or ORs are declared, their logarithms are weighted. You should only use this option if you are satisfied that the weights are meaningful. second(model or estimates and description) (v9 update) A second analysis may be performed using another method, using fixed, random or peto. Alternatively, the user may define their own estimate and 95% CI based on calculations performed externally to metan, along with a description of their method, in the format es lci uci description. The results of this analysis are then displayed in the table and 4 forest plot. Note that if by is used then sub-estimates from the second method are not displayed with user defined estimates, for obvious reasons. first(estimates and description) (v9 update) Use of this command completely changes the way metan operates, as results are no longer based on any standard methods. The user defines their own estimate, 95% CI, and description as in the above and must supply their own weightings using wgt(weightvar) to control display of box sizes. Note that data must be supplied in the 2 or 3 variable syntax (theta se_theta or es lci uci) and by may not be used used for obvious reasons. +-----------------+ ----+ Continuous data +-------------------------------------------------cohen pools standardised mean differences by the method of Cohen (the default). hedges pools standardised mean differences by the method of Hedges. glass pools standardised mean differences by the method of Glass. nostandard pools unstandardized mean differences. fixed specifies a fixed-effects model using the inverse variance method (the default). random specifies a random-effects model using the DerSimonian and Laird method. nointeger denotes that the number of observations in each arm does not need to be an integer. By default, the first and fourth variables specified (containing N_intervention and N_control respectively) may occasionally be noninteger (see entry for nointeger under binary data). +--------+ ----+ Output +----------------------------------------------------------by(byvar) specifies that the meta-analysis is to be stratified according to the variable declared. sgweight specifies that the display is to present the percentage weights within each subgroup separately. By default metan presents weights as a percentage of the overall total. log reports the results on the log scale (valid for OR and RR analyses from raw data counts only). 5 nosubgroup indicates that no within-group results are to be presented. By default metan pools trials both within and across all studies. eform exponentiates all effect sizes and confidence intervals (valid only when the input variables are log odds-ratios or log hazard-ratios with standard error or confidence intervals). efficacy expresses results as the vaccine efficacy (the proportion of cases that would have been prevented in the placebo group that would have been prevented had they received the vaccination). Only available with odds ratios (OR) or risk ratios (RR). ilevel(#) specifies the coverage (e.g., 90, 95, 99 percent) for the individual trial confidence intervals. The default is $S_level. ilevel() and olevel() need not be the same. See set level. olevel(#) specifies the coverage (e.g., 90, 95, 99 percent) for the overall (pooled) trial confidence intervals. The default is $S_level. ilevel() and olevel() need not be the same. See set level. sortby(varlist) sorts by variable(s) in varlist. label([namevar=namevar], [yearvar=yearvar]) labels the data by its name, year, or both. Either or both option/s may be left blank. For the table display, the overall length of the label is restricted to 20 characters. The lcols() option will override this if specified. nokeep prevents the retention of study parameters in permanent variables (see saved results below). notable prevents display of table of results. nograph prevents display of graph. nosecsub (v9 update) prevents the display of subestimates using the second method if second() is used. Note that this is invoked automatically with user-defined estimates. +-------------+ ----+ Forest plot +-----------------------------------------------------effect(string) may be used when the effect size and its standard error are declared. This allows the graph to name the summary statistic used. nooverall revents display of overall effect size on graph (automatically enforces the nowt option). nowt prevents display of study weight on the graph. 6 nostats prevents display of study statistics on graph. counts (v9 update) displays data counts (n/N) for each group when using binary data, or the sample size, mean, and SD for each group if mean differences are used (the latter is a new feature). group1(string), group2(string) may be used with the counts option; the text should contain the names of the two groups. xlabel() (v9 update) defines x-axis labels. This has been modified so that any number of points may defined. Also, there are no longer any checks made as to whether these points are sensible, so the user may define anything if the force option is used. Points must be comma separated. xtick() adds tick marks to the x axis. Points must be comma separated. force forces the x-axis scale to be in the range specified by xlabel(). boxsca() (v9 update) controls box scaling. This has been modified slightly so that the default is 100 (as in a percentage) and may be increased or decreased as such (e.g., 80 or 120 for 20% smaller or larger respectively) nobox prevents a "weighted box" being drawn for each study and markers for point estimates only are shown. texts() (v9 update) specifies font size for text display on graph. This has been modified slightly so that the default is 100 (as in a percentage) and may be increased or decreased as such (e.g., 80 or 120 for 20% smaller or larger, respectively) +------------------------------------------------------+ ----+ Further options for the forest plot in the v9 update +------------lcols(varlist), rcols(varlist) define columns of additional data to the left or right of the graph. The first two columns on the right are automatically set to effect size and weight, unless suppressed using the options nostats and nowt. If counts is used this will be set as the third column. textsize() can be used to fine-tune the size of the text in order to acheive a satisfactory appearance. The columns are labelled with the variable label, or the variable name if this is not defined. The first variable specified in lcols() is assumed to be the study identifier and this is used in the table output. astext(#) specifies the percentage of the graph to be taken up by text. The default is 50 and the percentage must be in the range 10-90. double allows variables specified in lcols and rcols to run over two lines in the plot. This may be of use if long strings are to be used. 7 nohet prevents display of heterogeneity statistics in the graph. summaryonly shows only summary estimates in the graph (may be of use for multiple subgroup analyses) rfdist displays the confidence interval of the approximate predictive distribution of a future trial, based on the extent of heterogeneity. This incorporates uncertainty in the location and spread of the random effects distribution using the formula t(df) x sqrt(se2 + tau2) where t is the t-distribution with k-2 degrees of freedom, se2 is the squared standard error and tau2 the heterogeneity statistic. The CI is then displayed with lines extending from the diamond. Note that with <3 studies the distribution is inestimable and effectively infinite, thus displayed with dotted lines, and where heterogeneity is zero there is still a slight extension as the t-statistic is always greater than the corresponding normal deviate. For further information, see Higgins and Thompson (2001) rflevel(#) specifies the coverage (e.g., 90, 95, 99 percent) for the confidence interval of the predictive distribution. The default is $S_level. See set level. null(#) displays the null line at a user-defined value rather than 0 or 1. nulloff removes the null hypothesis line from the graph. favours(string # string) applies a label saying something about the treatment effect to either side of the graph (strings are separated by the # symbol). This replaces the feature available in b1title in the previous version of metan. firststats(string), secondstats(string) labels overall user-defined estimates when these have been specified. Labels are displayed in the position usually given to the heterogeneity statistics. boxopt(), diamopt(), pointopt(), ciopt(), olineopt() specify options for the graph routines within the program, allowing the user to alter the appearance of the graph. Any options associated with a particular graph command may be used, except some that would cause incorrect graph appearance. For example, diamonds are plotted using the twoway pcspike command, so options for line styles are available (see line options); however, altering the x-y orientation with the option horizontal or vertical is not allowed. So, diamopt(lcolor(green) lwidth(thick)) feeds into a command such as pcspike(y1 x1 y2 x2, lcolor(green) lwidth(thick)). boxopt() controls the boxes and uses options for a weighted marker (e.g., shape, colour, but not size). See marker_options. 8 diamopt() controls the diamonds and uses options for pcspike (not horizontal/vertical). See line_options. pointopt() controls the point estimate using marker options. See marker_options and marker_label_options. ciopt() controls the confidence intervals for studies using options for pcspike (not horizontal/vertical). See line_options. olineopt() controls the overall effect line with options for an additional line (not position). See line_options. classic specifies that solid black boxes without point estimate markers are used as in the previous version of metan. nowarning switches off the default display of a note warning that studies are weighted from random-effects anaylses. graph_options specifies overall graph options that would appear at the end of a twoway graph command. This allows the addition of titles, subtitles, captions, etc., control of margins, plot regions, graph size, aspect ratio, and the use of schemes. As titles may be added in this way, previous options, b2title, etc., are no longer necessary. See twoway_options. Options for labbe nowt declares that the plotted data points are to be the same size. percent displays the event rates as percentages rather than proportions. null draws a line corresponding to a null effect (ie p1=p2). or(#) draws a line corresponding to a fixed odds ratio of #. rd(#) draws a line corresponding to a fixed risk difference of #. rr(#) draws a line corresponding to a fixed risk ratio of #. See also the rrn() option. rrn(#) draws a line corresponding to a fixed risk ratio (for the nonevent) of #. The rr() and rrn() options may require explanation. Whereas the OR and RD are invariant to the definition of which of the binary outcomes is the "event" and which is the "nonevent", the RR is not. That is, while the command metan a b c d , or gives the same result as metan b a d c , or (with direction changed), an RR analysis does not. The L'Abbe plot allows the display of either or both to be superimposed risk difference. 9 logit is for use with the or() option; it displays the probabilities on the logit scale ie log(p/1-p). On the logit scale, the odds ratio is a linear effect, and so this makes it easier to assess the "fit" of the line. wgt(weightvar) specifies alternative weighting by the specified variable (default is sample size). symbol(symbolstyle) allows the symbol to be changed (see help symbolstyle) the default being hollow circles (or points if weights are not used). nolegend suppresses a legend being displayed (the default if more than one line corresponding to effect measures are specified). id(idvar) displays marker labels with the specified ID variable idvar. clockvar() and gap() may be used to fine-tune the display, which may become unreadable if studies are clustered together in the graph. textsize(#) increases or decreases the text size of the ID label by specifying # to be more or less than unity. The default is usually satisfactory but may need to be adjusted. clockvar(clockvar) specifies the position of idvar around the study point, as if it were a clock face (values must be integers; see clockposstyle). This may be used to organize labels where studies are clustered together. By default, labels are positioned to the left (9 o'clock) if above the null and to the right (3 o'clock) if below. Missing values in clockvar will be assigned the default position, so this need not be specified for all observations. gap(#) increases or decreases the gap between the study marker and the ID label by specifying # to be more or less than unity. The default is usually satisfactory but may need to be adjusted. graph_options are options for Stata 8 graphs (see help on graph). Remarks on metan For two or three variables, a variance-weighted analysis is performed in a similar fashion to the meta command; the two variable syntax is theta and SE(theta). The 3 variable syntax is theta, lower ci (theta), upper ci (theta). Note that in this situation "theta" is taken to be the logarithm of the effect size if the odds ratio or risk ratio is used. This differs from the equivalent in the meta command. This program does not assume the three variables need log transformation: if odds ratios or risk ratios are combined, it is up to the user to log-transform them first. The eform option may be used to change back to the original scale if 10 needed. By default the confidence intervals are assumed symmetric, and the studies are pooled by taking the variance to be equal to (CI width)/2z. Note that for graphs on the log scale (that is, ORs or RRs), values outside the range [10e-8,10e8] are not displayed, and similarly graphs of other measures (log ORs, RDs, SMDs) are restricted to the range [-10e8,10e8]. A confidence interval which extends beyond this, or the specified scale if force is used, will have an arrow added at the end of the range. Further notes on v9 update: If by is used with a string variable the stratification variable is not sorted alpha-numerically and the original order that the groups appear in the data is preserved. This may be of use if a particular display order is required; if not, sortby may be used. The option counts is now available for continuous data and displays sample size, mean and SD in each group. The estimate for heterogeneity between groups from a stratified analysis using the Mantel-Haenszel method, and arguably the Peto method, is invalid. Therefore this is not displayed in the output for either of these methods. Remarks on labbe By default the size of the plotting symbol is proportional to the sample size of the study. If weights are specified the plotting size will be proportional to the weight variable. Note that labbe has now been updated to version 8 graphics. All options work the same as in the previous version, and some minor graphics options have been added. Stored By default, metan adds the following new variables to the dataset: _ES _seES Effect size (ES) Standard error of ES or, when OR or RR are specfied: _selogES the standard error of its logarithm _LCI Lower confidence limit for ES _UCI Upper confidence limit for ES _WT Study percentage weight _SS Study sample size Examples All examples use a simulated example dataset (Ross Harris 2006) . use http://fmwww.bc.edu/repec/bocode/m/metan_example_data 11 Risk difference from raw cell counts, random effects model, "label" specification with counts displayed . metan tdeath tnodeath cdeath cnodeath, rd random label(namevar=id, yearid=year) counts (click to run) Sort by year, use data columns syntax. Text size increased, specify percentage of graph as text and two lines per study; suppress stats, weight, heterogeneity stats and table. . metan tdeath tnodeath cdeath cnodeath, sortby(year) lcols(id year country) rcols (population) textsize(110) astext(60) double nostats nowt nohet notable (click to run) Analyze continuous data (6 parameter syntax), stratify by type of study, with weights summing to 100 within sub group, second analysis specified, display random effects distribution, show raw data counts, display "favours treatment vs. favours control" labels . metan tsample tmean tsd csample cmean csd, by(type_study) sgweight fixed second(random) rfdist counts label(namevar = id) favours(Treatment reduces blood pressure # Treatment increases blood pressure) (click to run) Generate log odds ratio and standard error, analyse with 2 parameter syntax. Graph has exponential form, scale is forced within set limits and ticks added, effect label specified. . gen logor = ln( (tdeath*cnodeath)/(tnodeath*cdeath) ) . gen selogor = sqrt( (1/tdeath) + (1/tnodeath) + (1/cdeath) + (1/cnodeath) ) . metan logor selogor, eform xlabel(0.5, 1, 1.5, 2, 2.5) force xtick(0.75, 1.25, 1.75, 2.25) effect(Odds ratio) (click to run) Display diagnostic test data with 3 parameter syntax. Weight is number of positive diagnoses, axis label set, and null specified at 50%. Overall effect estimate is not displayed, graph for visual examination only. . metan percent lowerci upperci, wgt(n_positives) xlabel(0,10,20,30,40,50,60,70,80,90,100) force 12 null(50) label(namevar=id) nooverall notable title(Sensitivity, position(6)) (click to run) User has analysed data with a nonstandard technique and supplied effect estimates, weights and description of statistics. The scheme "Economist" has been used. . metan OR ORlci ORuci, wgt(bweight) first(0.924 0.753 1.095 Bayesian) firststats(param V=3.86, p=0.012) label(namevar=id) xlabel(0.25, 0.5, 1, 2, 4) force null(1) aspect(1.2) scheme(economist) (click to run) Variable counts defined showing raw data. Options to change the box, effect estimate marker and confidence interval used, and the counts variable has been attached to the estimate marker as a label. . gen counts = ". " + string(tdeath) + "/" + string(tdeath+tnodeath) + ", " + string(cdeath) + "/" + string(cdeath+cnodeath) . metan tdeath tnodeath cdeath cnodeath, lcols(id year) notable boxopt( mcolor(forest_green) msymbol(triangle) ) pointopt( msymbol(triangle) mcolor(gold) msize(tiny) mlabel(counts) mlabsize(vsmall) mlabcolor(forest_green) mlabposition(1) ) ciopt( lcolor(sienna) lwidth(medium) ) (click to run) L'Abbe plot with labelled axes and display of risk ratio and risk difference. . labbe tdeath tnodeath cdeath cnodeath, xlabel(0,0.25,0.5,0.75,1) ylabel(0,0.25,0.5,0.75,1) rr(1.029) rd(0.014) null (click to run) Authors Michael J Bradburn, Jonathan J Deeks, Douglas G Altman. Centre for Statistics in Medicine, University of Oxford, Wolfson College Annexe, Linton Road, Oxford, OX2 6UD, UK Version 9 update 13 Ross J Harris (rossharris1978@yahoo.co.uk), Roger M Harbord, Jonathan A C Sterne. Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK Other updates and improvements to code and help file Patrick Royston. MRC Clinical Trials Unit, 222 Euston Road, London, NW1 2DA Acknowledgements Thanks to Vince Wiggins, Kit Baum, and Jeff Pitblado of Statacorp who offered advice and helped facilitate the version 9 update. Thanks also to all the people who helped with beta-testing and made comments and suggested improvements. References Higgins, J. P. T. , S. G. Thompson, J. J. Deeks, and D. G. Altman. 2003. Measuring inconsistency in meta-analyses. British Medical Journal 327: 557-560. Higgins, J. P. T., and S. G. Thompson. 2001. Presenting random effects meta-analyses: Where we are going wrong? 9th International Cochrane Colloquium, Lyon, France. Also see Article: Stata Journal, volume 9, number 2: sbe24_3 Stata Journal, volume 8, number 1: sbe24_2 Stata Technical Bulletin 45: sbe24.1 Stata Technical Bulletin 44: sbe24 Online: metan7, metannt meta (if installed), metacum (if installed), metareg (if installed), metabias (if installed), metatrim (if installed), metainf (if installed), galbr (if installed), metafunnel (if installed) 14 metacum: Cumulative meta-analysis, with graphics metacum varlist [if] [in] [, [binary_data_options | continuous_data_options | precalculated_effect_estimates_options] measure_and_model_option output_options forest_plot_options] binary_data_options or rr rd fixed random fixedi randomi peto nointeger cc(#) continuous_data_options cohen hedges glass nostandard fixed random nointeger precalculated_effect_estimates_options fixed random measure_and_model_option wgt(wgtvar) output_options by(byvar) log eform ilevel(#) sortby(varlist) label([namevar=namevar], [yearvar=yearvar]) notable nograph forest_plot_options xlabel(#,...) xtick(#,...) textsize(#) nowt nostats counts group1(string) group2(string) effect(string) force lcols(varlist) rcols(varlist) astext(#) double summaryonly null(#) nulloff favours(string # string) pointopt(marker_options | marker_label_options) ciopt(line_options) olineopt(line_options) classic nowarning graph_options Description metacum provides cumulative pooled estimates and confidence limits obtained from fixed or random effects meta-analysis and plots the cumulative pooled estimates in the style of Lau et al. (1992). This updated version requires that metan is installed, for which metacum 15 now acts as a wrapper. As such the syntax is very similar, allowing the user to supply data in a variety of formats. Version 9 graphics are displayed and most of the options for metan, and many general graphics options, are permitted. This help file is very similar to that of metan, although with the omission of some options. metacum requires either two, three, four or six variables to be declared. When four variables are specified these correspond to the number of events and non-events in the experimental group followed by those of the control group, and analysis of binary data is performed on the 2x2 table. With six variables, the data are assumed continuous and to be the sample size, mean and standard deviation of the experimental group followed by those of the control group. If three variables are specified these are assumed to be the effect estimate and its lower and upper confidence interval, and it is suggested that these are log transformed for odds ratios or risk ratios and the eform option used. If two variables are specified these are assumed to be the effect estimate and standard error; again, it is recommended that odds ratios or risk ratios are log transformed. Options - binary_data_options or pools ORs. rr pools RRs; this is the default. rd pools risk differences. fixed specifies a fixed-effect model using the Mantel-Haenszel method; this is the default. random specifies a random-effects model using the DerSimonian and Laird method, with the estimate of heterogeneity being taken. fixedi specifies a fixed-effect model using the inverse-variance method. randomi specifies a random-effects model using the DerSimonian and Laird method, with the estimate of heterogeneity being taken from the inverse-variance fixed-effect model. peto specifies that the Peto method is used to pool ORs. nointeger allows the cell counts to be nonintegers. This option may be useful when a variable continuity correction is sought for studies containing zero cells but also may be used in other circumstances, such as where a cluster-randomized trial is to be incorporated and the "effective sample size" is less than the total number of 16 observations. cc(#) defines a fixed-continuity correction to add where a study contains a zero cell. By default, metan8 adds 0.5 to each cell of a trial where a zero is encountered when using inverse-variance, DerSimonian and Laird, or Mantel-Haenszel weighting to enable finite variance estimators to be derived. However, the cc() option allows the use of other constants (including none). See also the nointeger option. - continuous_data_options cohen pools standardized mean differences by the Cohen method; this is the default. hedges pools standardized mean differences by the Hedges method. glass pools standardized mean differences by the Glass method. nostandard pools unstandardized mean differences. fixed specifies a fixed-effect model using the Mantel-Haenszel method; this is the default. random specifies a random-effects model using the DerSimonian and Laird method, with the estimate of heterogeneity being taken. nointeger denotes that the number of observations in each arm does not need to be an integer. By default, the first and fourth variables specified (containing N_intervention and N_control, respectively) may occasionally be noninteger (see nointeger under binary data). - precalculated_effect_estimates_options fixed specifies a fixed-effect model using the Mantel-Haenszel method; this is the default. random specifies a random-effects model using the DerSimonian and Laird method, with the estimate of heterogeneity being taken. - measure_and_model_option wgt(wgtvar) specifies alternative weighting for any data type. The effect size is to be computed by assigning a weight of wgtvar to the studies. When RRs or ORs are declared, their logarithms are weighted. This option should be used only if you are satisfied that the weights are meaningful. - output_options by(byvar) specifies that the meta-analysis is to be stratified according 17 to the variable declared. log reports the results on the log scale (valid only for ORs and RRs analyses from raw data counts). eform exponentiates all effect sizes and confidence intervals (valid only when the input variables are log-ORs or log-hazard ratios with standard error or confidence intervals). ilevel(#) specifies the coverage (e.g., 90%, 95%, 99%) for the individual trial confidence intervals; the default is $S_level. See set level. sortby(varlist) sorts by variable(s) in varlist. label([namevar=namevar], [yearvar=yearvar]) labels the data by its name, year, or both. Either or both variable lists may be left blank. For the table display, the overall length of the label is restricted to 20 characters. If the lcols() option is also specified, it will override the label() option. notable prevents the display of a results table. nograph prevents the display of a graph. - forest_plot_options xlabel(#,...) defines x-axis labels. This option has been modified so that any number of points may be defined. Also, checks are no longer made as to whether these points are sensible, so the user may define anything if the force option is used. Points must be comma separated. xtick(#,...) adds tick marks to the x-axis. Points must be comma separated. textsize(#) specifies the font size for the text display on the graph. This option has been modified so that the default is textsize(100) (as in 100%) and the percentage may be increased or decreased (e.g., 80 or 120 for 20% smaller or larger, respectively). nowt prevents the display of study weight on the graph. nostats prevents the display of study statistics on the graph. counts displays data counts (n/N) for each group when using binary data or the sample size, mean, and standard deviation for each group if mean differences are used (the latter is a new feature). group1(string) and group2(string) may be used with the counts option, and the text should contain the names of the two groups. 18 effect(string) allows the graph to name the summary statistic used when the effect size and its standard error are declared. force forces the x-axis scale to be in the range specified by xlabel(). lcols(varlist) and rcols(varlist) define columns of additional data to the left or right of the graph. The first two columns on the right are automatically set to effect size and weight, unless suppressed by using the options nostats and nowt. If counts is used, this will be set as the third column. textsize() can be used to fine-tune the size of the text to achieve a satisfactory appearance. The columns are labeled with the variable label or the variable name if this is not defined. The first variable specified in lcols() is assumed to be the study identifier and this is used in the table output. astext(#) specifies the percentage of the graph to be taken up by text. The default is 50%, and the percentage must be in the range 10-90. double allows variables specified in lcols() and rcols() to run over two lines in the plot. This option may be of use if long strings are used. summaryonly shows only summary estimates in the graph. This option may be of use for multiple subgroup analyses. null(#) displays the null line at a user-defined value rather than at 0 or 1. nulloff removes the null hypothesis line from the graph. favours(string # string) applies a label saying something about the treatment effect to either side of the graph (strings are separated by the # symbol). This option replaces the feature available in b1title in the previous version of metan. pointopt(marker_options), ciopt(line_options), and olineopt(line_options) specify options for the graph routines within the program, allowing the user to alter the appearance of the graph. Any options associated with a particular graph command may be used, except some that would cause incorrect graph appearance. For example, diamonds are plotted using the twoway pcspike command, so options for line styles are available (see line options); however, altering the x-y orientation with the option horizontal or vertical is not allowed. So, ciopt(lcolor(green) lwidth(thick)) feeds into a command such as pcspike(y1 x1 y2 x2, lcolor(green) lwidth(thick)) pointopt(marker_options) controls the point estimate by using marker options. See marker_options and marker_label_options. ciopt(line_options) controls the confidence intervals for studies by 19 using options for twoway pcspike (not horizontal/vertical). See line_options. olineopt(line_options) controls the overall effect line with options for another line (not position). See line_options. classic specifies that solid black boxes without point estimate markers are used, as in the previous version of metan. nowarning switches off the default display of a note warning that studies are weighted from random-effects analyses. graph_options are any of the options documented in [G] twoway_options. These allow the addition of titles, subtitles, captions, etc.; control of margins, plot regions, graph size, aspect ratio; and the use of schemes. Because titles may be added with graph_options, previous options such as b2title are no longer necessary. Remarks on metacum (calling metan) For two or three variables, a variance-weighted analysis is performed in a similar fashion to the meta command; the two variable syntax is theta and SE(theta). The 3 variable syntax is theta, lower ci (theta), upper ci (theta). Note that in this situation "theta" is taken to be the logarithm of the effect size if the odds ratio or risk ratio is used. This differs from the equivalent in the meta command. This program does not assume the three variables need log transformation: if odds ratios or risk ratios are combined, it is up to the user to log-transform them first. The eform option may be used to change back to the original scale if needed. By default the confidence intervals are assumed symmetric, and the studies are pooled by taking the variance to be equal to (CI width)/2z. Note that for graphs on the log scale (that is, ORs or RRs), values outside the range [10e-8,10e8] are not displayed, and similarly graphs of other measures (log ORs, RDs, SMDs) are restricted to the range [-10e8,10e8]. A confidence interval which extends beyond this, or the specified scale if force is used, will have an arrow added at the end of the range. Examples All examples use a simulated example dataset (Ross Harris 2006) . use http://fmwww.bc.edu/repec/bocode/m/metan_example_data Risk difference from raw cell counts, random effects model, "label" specification 20 . metacum tdeath tnodeath cdeath cnodeath, rd random label(namevar=id, yearid=year) (click to run) Generate log odds ratio and standard error. Graph has exponential form, scale is forced within set limits and ticks added. Data columns syntax used and effect label specified. . gen logor = ln( (tdeath*cnodeath)/(tnodeath*cdeath) ) . gen selogor = sqrt( (1/tdeath) + (1/tnodeath) + (1/cdeath) + (1/cnodeath) ) . metacum logor selogor, eform xlabel(0.6, 0.8, 1, 1.2, 1.4, 1.6) force xtick(0.7, 0.9, 1.1, 1.3, 1.5) lcols(id year country) effect(Odds ratio) (click to run) Reference Lau, J., E. M. Antman, J. Jimenez-Silva, F. Mosteller, and T. C. Chalmers. 1992. Cumulative meta-analysis of therapeutic trials for myocardial infarction. New England Journal of Medicine 327: 248-254. Authors First version Jonathan A. C. Sterne Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK Version 9 update Ross J. Harris Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK Also see Article: Stata Journal, volume 9, number 1: sbe22_1 Stata Technical Bulletin 44: sbe24 Online: metan, metannt (if installed), meta (if installed), metareg (if installed), metabias (if installed), metatrim (if installed), metainf (if installed), galbr (if installed), metafunnel (if installed) 21 metareg -- Meta-analysis regression (revised) Syntax metareg depvar [indepvars] [if] [in] wsse(varname) [, eform graph randomsize noconstant mm reml eb knapphartung z tau2test level(#) permute(# [, univariable detail joint(varlist1 [| varlist2 ...])]) log maximize_options] by can be used with metareg; see [D] by. Description metareg performs random-effects meta-regression using aggregate-level data. From a more abstract perspective, it extends vwls by estimating an extra additive component of variance tau2: y_i = a + B*x_i + u_i + e_i where a is a constant, u_i is a normal error term with known standard deviations wsse_i that may vary across units, and e_i is a normal error with variance tau2 to be estimated, assumed equal across units. This is a similar model to those fit by the xt commands, except that the within-unit data have been summarized by an effect estimate and its standard error for each unit i. Options wsse(varname) specifies the variable containing the standard error of depvar within each study (within-study standard error). All values of varname must be greater than zero. wsse() is required. eform indicates to output the exponentiated form of the coefficients and to suppress reporting of the constant. This option may be useful when depvar is the logarithm of a ratio measure, such as a log odds-ratio or a log risk-ratio. graph requests a line graph of fitted values plotted against the first covariate in indepvars, together with the estimates from each study represented by circles. By default, the circle sizes depend on the precision of each estimate (the inverse of its within-study variance), which is the weight given to each study in the fixed-effects model. randomsize is for use with the graph option. It specifies that the size 22 of the circles will depend on the weights in the random-effects model rather than the precision of each estimate. These random-effects weights depend on the estimate of tau2. - The remaining options will mainly be of interest to more advanced users: noconstant suppresses the constant term (intercept). This is rarely appropriate in meta-regression. The mm, reml, and eb options are alternatives that specify the method of estimation of the additive (between-study) component of variance tau2. mm specifies the use of method of moments to estimate the additive (between-study) component of variance tau2; this is a generalization of the DerSimonian and Laird (1986) method commonly used for random-effects meta-analysis. For speed, this is the default when the permute() option is specified, because it is the only noniterative method. reml specifies the use of residual maximum likelihood (REML) to estimate the additive (between-study) component of variance tau2. This is the default unless the permute() option is specified. This revised version uses Stata's maximum likelihood facilities to maximize the REML log likelihood. It will therefore not give identical results to the previous version of metareg, which used an approximate iterative method. eb specifies the use of the "empirical Bayes" method to estimate tau2 (Morris 1983). knapphartung makes a modification to the variance of the estimated coefficients suggested by Knapp and Hartung (2003), accompanied by the use of a t distribution in place of the standard normal distribution when calculating p-values and confidence intervals. This is the default unless the permute() option is specified. z requests that the knapphartung modification not be applied and that the standard normal distribution be used to calculate p-values and confidence intervals. This is the default when the permute() option is specified with a fixed-effects model. tau2test adds to the output two tests of tau2 = 0. The first is based on the residual heterogeneity statistic, Q_res. The second (not available if the mm option is also specified) is a likelihood-ratio test based on the REML log likelihood. These are two tests of the same null hypothesis (the fixed-effects model with tau2 = 0), but the alternative hypotheses are different, as are the distributions of the test statistics under the null, so close agreement of the two tests is not guaranteed. Both tests are typically of little interest because it is more helpful to quantify heterogeneity than to test for 23 it. level(#) specifies the confidence level, as a percentage, for confidence intervals. The default is level(95) or as set by set level. permute(...) calculates p-values by using a Monte Carlo permutation test. See Option for permutation test for more information about the option. log requests the display of the iteration log during estimation of tau2. This is ignored if the mm option is specified, because this uses a noniterative method. maximize_options are ignored unless estimation of tau2 is by REML. These options control the maximization process; see maximize. You should never need to specify them; they are supported only in case problems in the REML estimation of tau2 are ever reported or suspected. Option for permutation test The permute() option calculates p-values by using a Monte Carlo permutation test, as recommended by Higgins and Thompson (2004). To address multiple testing, permute() also calculates p-values for the most- to least-significant covariates, as the same authors also recommend. The syntax of permute() is permute(# [, univariable detail joint(varlist1 [| varlist2 ...])]) where # is required and specifies the number of random permutations to perform. Larger values give more precise p-values but take longer. There are three suboptions: univariable indicates that p-values should be calculated for a series of single covariate meta-regressions of each covariate in varlist separately, instead of a multiple meta-regression of all covariates in varlist simultaneously. detail requests more detailed output in the style given by permute. joint(varlist1 [| varlist2 ...]) specifies that a permutation p-value should also be computed for a joint test of the variables in each varlist. The eform, level(), and z options have no effect when the permute() option is specified. 24 Syntax of predict The syntax of predict following metareg is predict [type] newvar [if] [in] [, statistic] where statistic is xb fitted values; the default stdp standard error of the prediction stdf standard error of the forecast u predicted random effects ustandard standardized predicted random effects xbu prediction including random effects stdxbu standard error of xbu hat leverage (diagonal elements of hat matrix) These statistics are available both in and out of sample; type predict ... if e(sample) ... if wanted only for the estimation sample. Options for predict xb, the default, calculates the linear prediction, x_i*b, that is, the fitted values excluding the random effects. stdp calculates the standard error of the prediction (the standard error of the fitted values excluding the random effects). stdf calculates the standard error of the forecast. This gives the standard deviation of the predicted distribution of the true value of depvar in a future study, with the covariates given by varlist. stdf^2 = stdp^2 + tau2. u calculates the predicted random effects, u_i. These are the best linear unbiased predictions of the random effects, also known as the empirical Bayes (or posterior mean) estimates of the random effects, or as shrunken residuals. ustandard calculates the standardized predicted random effects, i.e., the predicted random effects, u_i, divided by their (unconditional) standard errors. These may be useful for diagnostics and model checking. xbu calculates the prediction including random effects, a + B*x_i + u_i, also known as the empirical Bayes estimates of the effects for each study. stdxbu calculates the standard error of the prediction including random 25 effects. hat calculates the leverages (the diagonal elements of the projection hat matrix). Saved results When the permute() option is not specified, metareg saves the following in e(): Scalars e(N) e(df_m) e(df_Q) e(df_r) e(remll) e(chi2_c) e(F) e(tau2) e(Q) e(I2) e(q_KH) e(remll_c) e(tau2_0) e(chi2) Macros e(cmd) e(predict) e(wsse) e(depvar) e(method) e(properties) Matrices e(b) e(V) Functions e(sample) number of observations model degrees of freedom degrees of freedom for test of Q=0 residual degrees of freedom (if t tests used) REML log likelihood chi^2 for comparison test model F statistic estimate of tau2 Cochran's Q I-squared Knapp-Hartung variance modification factor REML log likelihood, comparison model tau2, constant-only model model chi^2 metareg program used to implement predict name of wsse() variable name of dependent variable REML, Method of moments, or Empirical Bayes bV coefficient vector variance-covariance matrix of estimators marks estimation sample Examples . metareg logrr latitude, wsse(selogrr) eform . metareg logrr latitude, wsse(selogrr) graph . metareg smd abstract duration itt, wsse(sesmd) permute(10000) 26 . metareg smd abstract duration itt, wsse(sesmd) permute(1000, univariable) . xi: metareg logor i.group, wsse(selogor) permute(1000, joint(i.group)) Note metareg is programmed as a Stata estimation command and so supports many of the commands listed under estcom and postest (except when the permute() option is used). One deliberate exception is lrtest, which is not appropriate after metareg (because the REML log likelihood cannot be used to compare models with different fixed effects, while the method of moments is not based on a likelihood). For this reason, when the REML method is used, the iteration log showing the log likelihood is suppressed by default; specify the log option if you wish to see it. References DerSimonian, R., and N. Laird. 1986. Meta analysis in clinical trials. Controlled Clinical Trials 7: 177-188. Higgins, J. P. T, and S. G. Thompson. 2004. Controlling the risk of spurious findings from meta-regression. Statistics in Medicine 23: 1663-1682. Knapp, G., and J. Hartung. 2003. Improved tests for a random effects meta-regression with a single covariate. Statistics in Medicine 22: 2693-2710. Morris, C. N. 1983. Parametric empirical Bayes inference: Theory and applications. Journal of the American Statistical Association 78: 47-55. Sharp, S. 1998. sbe23: Meta-analysis regression. Stata Technical Bulletin 42: 16-22. Reprinted in Stata Technical Bulletin Reprints, vol. 7, pp. 148-155. College Station, TX: Stata Press. Author Roger M. Harbord Department of Social Medicine University of Bristol, UK roger.harbord@bristol.ac.uk Acknowledgments 27 This is a substantial revision of the original version of metareg written by Stephen Sharp (1998), who gave his permission to release this version under the same name and to incorporate his code. Julian Higgins gave advice on the permutation test. Aijing Shang tested early versions and made helpful suggestions. Portions of the new code borrow ideas from official Stata commands such as nbreg, and I thank StataCorp for making such code visible to the user. A dialog box, written by Thomas J. Steichen, is available for the original version of the metareg command. Also see Article: Stata Journal, volume 8, number 4: sbe23_1, Stata Technical Bulletin 42: sbe23 Manual: [R] meta, [R] permute Online: [R] vwls, [R] permute, meta (if installed), metan (if installed), meta_dialog (if installed) 28 metafunnel Funnel plots for meta-analysis metafunnel { theta { se | var } | exp(theta) { ll ul [cl] }} [if exp] [in range] [, by(by_var) [var | ci] noline forcenull reverse eform egger graph_options ] Description metafunnel plots funnel plots. These graphical displays are used to examine whether the results of a meta-analysis may have been affected by publication or other types of bias. The syntax is based on the same framework as for the meta, metabias, metacum, and metatrim commands. The user provides the effect estimate theta and either its standard error, se, or its variance, var. Alternatively, the user may provide exp(theta), its confidence interval (ll, ul), and, optionally, the confidence level. For more details, see help meta. Options by(by_var) displays subgroups according to the value of by_var. The legend displays the value labels for the levels of by_var if these are present; otherwise, it displays the value of each level of by_var. var and ci indicate that instead of the standard error of theta, the user supplied the variance of theta or confidence interval for exp(theta). For more details, see help meta. noline specifies that pseudo 95% confidence interval lines not be included in the plot. The default is to include them. forcenull forces the vertical line at the center of the funnel to be plotted at the null treatment effect of zero (1 when the treatment effect is exponentiated). The default is for the line to be plotted at the value of the fixed-effect summary estimate. reverse inverts the funnel plot so that larger studies are displayed at the bottom of the plot with smaller studies at the top. This may also be achieved by specifying noreverse as part of the yscale(axis_description) graphics option. eform exponentiates the treatment effect theta and displays the horizontal axis (treatment effect) on a log scale. This is useful for displaying ratio measures, such as odds ratios and risk ratios. 29 egger adds the fitted line corresponding to the regression test for funnel-plot asymmetry proposed by Egger et al. (1997) and implemented in metabias. This option may not be combined with the by() option. graph_options can be most of the options allowed by the graph twoway scatter command, such as marker_label_options. If option egger if specified, the look of the fitted line can be changed using any of the connect_options that start with cl*. Remarks Funnel plots are simple graphical displays of a measure of study size on the vertical axis against intervention or treatment effect on the horizontal axis. The name "funnel plot" is based on the fact that the precision in the estimation of the underlying intervention or treatment effect will increase as the size of component studies increases. Results from small studies will therefore scatter more widely, with the spread narrowing among larger studies. In the absence of bias, the plot will resemble a symmetrical inverted funnel. If there is bias, for example, because smaller studies showing no statistically significant effects remain unpublished, then such publication bias will lead to an asymmetrical appearance of the funnel plot. It should be noted that although funnel plots have traditionally been used to examine evidence for publication bias, funnel-plot asymmetry may reflect other types of bias or even result from the true intervention or treatment effect differing between small and large studies. They should, thus, be seen as displaying the evidence for "small study effects" in general rather than publication bias in particular. These issues are discussed by Egger et al. (1997) and Sterne, Egger, and Davey Smith (2001). metafunnel uses the same syntax as other meta-analysis commands, such as meta, metabias, metainf, and metatrim. The user provides an estimate of the treatment or intervention effect, theta, together with its associated standard error se (the default) or variance var, in which case the var option should be specified. Alternatively, the user provides a risk ratio or odds ratio (exp(theta), its confidence interval (ll, ul), and, optionally, the confidence level. The funnel plots are displayed in line with meta-analytic convention and the recommendations of Sterne and Egger (2001). The effect of the treatment or intervention in each study: The horizontal axis is plotted against the study size, as measured by the standard error of the treatment or intervention effect. The vertical axis is reversed so that larger studies are displayed 30 towards the top of the graph (this behavior may be changed using the reverse option). Users who wish to plot the treatment effect on the vertical axis should use the graph(begg) option of the metabias command. The funnel command, which is part of the metan package, also provides an alternative way to draw funnel plots. The plots include pseudo-95% confidence interval lines, which are drawn around the summary fixed-effect estimate of the intervention or treatment effect. The lines may be omitted using the nolines option. The user may also specify that the pseudo confidence limits are centered around a zero intervention effect using the forcenull option. When the eform option is used, the label of the horizontal axis (treatment effect, theta) is changed accordingly, unless there is a variable label for theta or the xtitle(axis_title) graphics option is used. By default, the subtitle "Funnel plot with pseudo 95% confidence limits" is displayed (or simply "Funnel plot" if the nolines option is specified). This may be changed using the graphics option subtitle(tinfo). Examples . metafunnel meandiff semeandiff . metafunnel logor selogor, eform xtitle("Odds ratio (log scale)") . metafunnel sttd stderr, by(dose) subtitle(Funnel plot with subgroups) forcenull . metafunnel logor varlogor, var reverse nolines xtitle(log odds ratio) Acknowledgments metafunnel was written by Jonathan Sterne and Roger Harbord, University of Bristol. Portions of the code were originally written by Tom Steichen, who also gave helpful comments on an early version of the command and provided the dialog. Nick Cox provided extensive programming advice. References Egger, M., G. Davey Smith, M. Schneider, and C. Minder. 1997. Bias in 31 meta-analysis detected by a simple, graphical test. British Medical Journal 315: 629-634. Sterne, J. A. C., M. Egger, and G. Davey Smith. 2001. Investigating and dealing with publication and other biases in meta-analysis. British Medical Journal 323: 101-105. Sterne, J. A. C. and M. Egger. 2001. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. Journal of Clinical Epidemiology 54: 1046-1055. Also see Online: help for meta, metabias, metainf, metatrim, metan, funnel (if installed) 32 confunnel Realce en el gráfico en embudo de los contornos de significación estadística Syntax confunnel varname1 varname2 [if] [in] [, options] options description ------------------------------------------------------------------------contours(numlist) specify significance levels of the contours to be plotted; default is 1%, 5%, and 10% significance levels contcolor(colorstyle) specify color of the contour lines if shadedcontours is not specified extraplot(plots) specify additional plots to overlay the funnel plot functionlowopts(options) pass options to the twoway function commands used to draw the contours functionuppopts(options) pass options to the twoway function commands used to draw the contours legendlabels(labels) specify labels in the legend for added items legendopts(options) specify options that affect the plot legend metric(se|invse|var|invvar) the scale of the y axis; either se, invse, var, or invvar onesided(lower|upper) lower- or upper-tailed, one-sided significance contours scatteropts(options) specifies any of the options documented in scatter shadedcontours specify shaded, instead of black, contour lines [no]shadedregions specify or suppress shaded regions between the contours solidcontours specify solid, instead of dashed, contour lines studylab(string) the legend label for the scatter points twowayopts(twoway_options) pass options to the twoway plot twoway_options pass options to the twoway plot ------------------------------------------------------------------------- Description confunnel plots contour-enhanced funnel plots for assessing small-study reporting bias in meta-analysis. 33 Vontours illustrating the statistical significance of the study-effect estimates are plotted from either a one- or two-tailed test. confunnel requires two input variables; varname1 a variable of effect estimates such as log odds ratios and varname2 a variable of the standard errors of the effect estimates. The y axis can be specified using different scales, namely, standard error, inverse standard error, variance, and inverse variance. Options contours(numlist) specifies the significance levels of the contours to be plotted; the default is contours(1 5 10). There are only distinct line patterns for 8 significance levels. See numlist. contcolor(colorstyle) specifies the color of the contour lines if noshadedcontours is specified. See [G] colorstyle. extraplot(plots) specifies one or multiple additional plots to be overlaid on the funnel plot. functionlowopts(options) and functionuppopts(options) pass options to the twoway function commands used to draw the significance contours; for example, the line widths can be changed. See [G] graph twoway function. legendlabels(labels) specifies labels in the legend for extra elements added to the funnel plot. The option will take the form: legendlabels(`"8 "new label""'). legendopts(options) passes options to the plot legend. See [G] legend_option. metric(se|invse|var|invvar) specifies the metric of the y axis of the plot. se, invse, var, and invvar stand for standard error, inverse standard error, variance, and inverse variance, respectively; the default is se. onesided(lower|upper) can be lower or upper, for lower-tailed or upper-tailed levels of statistical significance, respectively. If unspecified, two-sided significance levels are used to plot the contours. scatteropts(options) specifies any of the options documented in [G] graph twoway scatter. shadedcontours specifies shaded contour lines; specify with the noshadedregions option. 34 [no]shadedregions specifies or suppresses shaded regions between the contours. This option provides plots that are more similar to those in the original paper by Peters et al. (2008) and the Cochrane Handbook. A plot with shadedregions is now the default. solidcontours specifies solid contour lines; specify with the shadedcontours and noshadedregions option. studylab(string) specifies the label for the scatter points in the legend. If not specified the default is "Studies". twowayopts(options) specifies options passed to the twoway plotting function; see [G] twoway_options. twoway_options see [G] twoway_options. As of confunnel version 1.0.5 twoway options can be specified at the end of the options and do not have to be within twowayopts. Remarks The confunnel command is based on an idea by Peters et al. (2008) to superimpose contours of statistical significance on a funnel plot in a meta-analysis. The command was explained in Palmer et al. (2008). Superimposing contours on funnel plots has also been suggested by Spiegelhalter (2005) in a slightly different context. confunnel can be used in conjunction with the results of the metan, metatrim, and metabias commands. See meta in Stata version 10 for information about user-written commands for meta-analysis. Examples The following examples use the example dataset accompanying metan. . confunnel logOR selogOR (click to run) . confunnel logOR selogOR, noshadedregions (click to run) . confunnel logOR selogOR, solidcontours shadedcontours noshadedregions (click to run) . confunnel logOR selogOR, metric(invse) (click to run) . confunnel logOR selogOR, onesided(upper) noshadedregions 35 (click to run) References Palmer, T. M., J. L. Peters, A. J. Sutton, and S. G. Moreno. 2008. Contour enhanced funnel plots for meta-analysis. Stata Journal 8: 242-254. Peters, J. L., A. J. Sutton, D. R. Jones, K. R. Abrams, and L. Rushton. 2008. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. Journal of Clinical Epidemiology. 61: 991-996. Spiegelhalter, D. J. 2005. Funnel plots for comparing institutional performance. Statistics in Medicine 24: 1185-1202. Sterne, J. A. C., and M. Egger. 2001. Funnel plots for detecting bias in meta-analysis: Guidelines on choice of axis. Journal of Clinical Epidemiology 54: 1046-1055. Sterne, J. A. C., and R. M. Harbord. 2004. Funnel plots in meta-analysis. Stata Journal 4: 127-141. Sterne, J. A. C., M. Egger, and D. Moher. 2008. Chapter 10: Addressing reporting biases; Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. Author Tom Palmer, MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, UK. tom.palmer@bristol.ac.uk. Jaime Peters wrote the first version of this command. Thanks to Santiago G. Moreno for testing the command. Please report any errors you may find. Also see Article: Stata Journal, volume 9, number 2: gr0033_1 Stata Journal, volume 8, number 2: gr0033 Online: metabias, metafunnel, metan (if installed) 36 metabias Syntax metabias varlist [if] [in], egger harbord peters begg [graph nofit or rr level(#) graph_options] As in the metan command, varlist should contain either four or two variables. When four variables are given, these are assumed to be cell counts for the 2 x 2 table in this order: cases and noncases for the experimental group, then cases and noncases for the control group (d1 h1 d0 h0). When two variables are specified, these are assumed to be the effect estimate and its standard error (theta se_theta). It is recommended that ratio-based effect estimates are log transformed as in metan. by is allowed with metabias; see [D] by. Description metabias performs updated regression tests for funnel plot asymmetry in meta-analysis. The Harbord test regresses Z/sqrt(V) against sqrt(V), where Z is the efficient score and V is Fisher's information (the variance of Z under the null hypothesis). The Peters test regresses the intervention effect estimate on 1/n with weights dh/n, where n is the total sample size, d is the number experiencing the event, and h is the number not experiencing the event. These can be calculated for the log odds-ratio or log risk-ratio, from 2 x 2 tables of binary outcomes. The Egger test is also implemented and performs a linear regression of the intervention effect estimates on their standard errors, weighting by 1/(variance of the intervention effect estimate). This test is recommended for intervention effects measured as mean differences but can suffer from false-positive test results when analyzing odds ratios because of the mathematical association between the log odds-ratio and its standard error. For completeness, the Begg test is also implemented, although this is widely accepted to be redundant because it suffers the same statistical problems as Egger's test but has lower power. Options egger, harbord, peters, and begg specify that the original Egger test, Harbord's modified test, Peters' test, or the rank correlation test proposed by Begg and Mazumdar (1994) be reported, respectively. There is no default; one test must be chosen. graph displays a Galbraith plot (the standard normal deviate of intervention effect estimate against its precision) for the original 37 Egger test or a modified Galbraith plot of Z/sqrt(V) versus sqrt(V) for Harbord's modified test. There is no corresponding plot for the Peters or Begg tests. nofit suppresses the fitted regression line and confidence interval around the intercept in the Galbraith plot. or (the default for binary data) uses odds ratios as the effect estimate of interest. rr specifies that risk ratios rather than odds ratios be used. This option is not available for the Peters test. level(#) specifies the confidence level, as a percentage, for confidence intervals. The default is level(95) or as set by set level. graph_options are any of the options documented in [G] graph twoway scatter. In particular, the options for specifying marker labels are useful. Examples . metabias d1 h1 d0 h0, or harbord . metabias tdeath tnodeath cdeath cnodeath, or harbord graph mlabel(trial) . metabias eventint noeventint eventcon noeventcon, or peters . metabias theta se_theta, egger Authors Roger Harbord, Department of Social Medicine, University of Bristol, UK Ross Harris, Centre for Infections, Health Protection Agency, London, UK Jonathan Sterne, Department of Social Medicine, University of Bristol, UK Reference Begg, C. B., and M. Mazumdar. 1994. Operating characteristics of a rank correlation test for publication bias. Biometrics 50: 1088-1101. History and note on dialog box This version of metabias revises and extends the previous package by Thomas Steichen, first released as sbe19 in STB 41 and updated through to sbe19.5. We are grateful for Tom's permission to release this version under the same name. The dialog box added to sbe19.5 (and to the distribution dated 20040409 38 on SSC) is not compatible with this revised and extended version of the package, which does not currently include a dialog box. Also see Article: Stata Journal, volume 9, number 2: sbe19_6 Stata Journal, volume 3, number 4: sbe19_5 Stata Technical Bulletin 61: sbe19.4 Stata Technical Bulletin 58: sbe19.3 Stata Technical Bulletin 57: sbe19.2 Stata Technical Bulletin 44: sbe19.1 Stata Technical Bulletin 41: sbe19 Online: metan (if installed), metafunnel (if installed), confunnel (if installed) 39 glst Generalized Least Squares for Trend… para estudios de tendencias de análisis de dosisrespuesta Syntax glst depvar dose [indepvars] [if] [in], se(varname) cov(n cases) {cc | ir | ci} [options] options description ------------------------------------------------------------------------* se(varname) variable containing estimate of standard error * cov(n cases) variables containing the information required to fit the covariances + cc case-control data + ir incidence-rate data + ci cumulative incidence data vwls variance-weighted least-squares estimation crudes crude relative risks and correlations pfirst(id study) pool-first method tstage(f|r) two-stage fixed- or random-effects meta-analysis ssest study-specific linear trend estimates random random-effects for the dose coefficient in an aggregate analysis level(#) set confidence level; default is level(95) eform generic label; exp(b); the default ------------------------------------------------------------------------* se() and cov() are required. + One of cc, ir, or ci is required for trend estimation. depvar contains log relative-risks; dose is the main covariate of interest and contains the exposure levels; and indepvars may contain other covariates, such as polynomial terms of dose or interaction terms. Description glst estimates log-linear dose-response regression models using generalized least squares for trend estimation of single or multiple summarized dose-response epidemiological studies, namely, case-control, incidence-rate, and cumulative incidence data. It differs from variance-weighted least squares (see [R] vwls) in that glst estimates a variance-covariance matrix of the beta coefficients, as proposed by 40 Greenland and Longnecker (1992). Options se(varname) specifies an estimate of the standard error of depvar, log relative-risks. All values of varname must be > 0. cov(n cases) specifies variables containing the information required to fit the covariances among the beta coefficients. At each exposure level, n is the number of subjects (controls plus cases) for case-control data (cc); or the total person-time for incidence-rate data (ir); or the total number of persons (cases plus noncases) for cumulative incidence data (ci). The cases variable contains the number of cases at each exposure level. cc specifies case-control data. It is required for trend estimation of one study unless the pfirst() option is specified. ir specifies incidence-rate data. It is required for trend estimation of one study unless the pfirst() option is specified. ci specifies cumulative incidence data. It is required for trend estimation of one study unless the pfirst() option is specified. vwls specifies variance-weighted least-squares (see [R] vwls) estimation, which assumes zero covariances among a series of log relative-risks; the default is generalized least squares. crudes specifies to calculate the vector of crude relative risks, and its variance-covariance and correlation matrices. This option also provides the relative differences (as percentages) between crude and adjusted relative risks and their correlation matrix. pfirst(id study) specifies the pool-first method with multiple summarized studies. The id variable is an indicator variable that assumes the same value across correlated parameters within a study. The study variable must take value 1 for case-control data, 2 for incidence-rate data, and 3 for cumulative incidence data. Within each group of parameters, the first observation is assumed to be the referent. This option allows the estimation either a fixed- or random-effects meta-regression model. tstage(f|r) specifies the two-stage fixed-effects (f) (inverse variance-weighted least squares) or random-effects (r) meta-analysis of dose-response linear trends (using the method of moments to estimate the between-study variance, tau2). This option can be specified only if pfirst() is also specified, and if only one covariate, namely, the dose variable, is included in the linear predictor. 41 ssest displays study-specific linear trend estimates. This option can be specified only if pfirst() is also specified. random specifies the iterative generalized least-squares method to fit a random-effects meta-regression model (aggregate analysis). Between-study variability of the dose coefficient is estimated with the moment estimator. This option can be specified only if pfirst() is specified. level(#) specifies the confidence level, as a percentage, for confidence intervals. The default is level(95) or as set by set level. eform reports coefficient estimates as exp(b) rather than b. Standard errors and confidence intervals are similarly transformed. Example Input data from table 1, page 1302 of Greenland and Longnecker (1992) . use http://nicolaorsini.altervista.org/stata/data/dose.dta, clear Go from 95% CI of odds ratios to 95% CI of log odds-ratios . gen double logor = log(adjor) . gen double logorlb = log(lb) . gen double logorub = log(ub) . gen double se = ((logorub - logorlb)/(2*invnorm(.975))) Trend estimation without correction for covariance of odds ratios . vwls logor dose in 2/4, sd(se) nocons . mat list e(V) Trend estimation with correction for covariance of log odds-ratios . glst logor dose, se(se) cov(N case) cc Check the variance-covariance matrix of log odds-ratios . mat list e(Sigma) Reference Greenland S. and M. P. Longnecker. 1992. Methods for trend estimation from summarized dose-reponse data, with applications to meta-analysis. American Journal of Epidemiology 135: 1301-1309. 42 Authors Nicola Orsini, Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Sweden Rino Bellocco, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden Sander Greenland, Department of Epidemiology, UCLA School of Public Health Support http://nicolaorsini.altervista.org nicola.orsini@ki.se Also see Article: Stata Journal, volume 9, number 2: st0096_2 Stata Journal, volume 9, number 1: st0096_1 Stata Journal, volume 6, number 1: st0096 Manual: [R] vwls Online: [R] vwls