Restricted maximum likelihood and maximum likelihood estimator for between-study heterogeneity implemented by calling rma.mv() from R package

**metafor**internallyR function pairwise() can be used to generate reduced data set with basic comparisons Rücker & Schwarzer (2014)

R function discomb() can be used with an R object created with pairwise()

- netmeta():
- use of ginv() instead of solve() to calculate pseudo inverse of Laplace matrix resulted in wrong results for some extreme network structures (bug was introduced in
**netmeta**, version 1.3-0)

- use of ginv() instead of solve() to calculate pseudo inverse of Laplace matrix resulted in wrong results for some extreme network structures (bug was introduced in
- netgraph.netmeta():
- highlighting more than one comparison (argument ‘highlight’) resulted in an error if argument ‘col.highlight’ was not of same length

- netmeta():
- new argument ‘method.tau’ to select estimation method for between-study variance
- new arguments ‘sd1’, ‘sd2’, ‘time1’, and ‘time2’ used to calculate variance-covariance matrix for REML and ML estimator of between-study heterogeneity
- do not calculate leverages for multi-arm studies

- netconnection():
- first argument can be of class ‘pairwise’

- pairwise():
- new arguments ‘reference.group’ and ‘keep.all.comparisons’
- first argument can be of class ‘pairwise’

- netgraph.netconnection():
- print subnetworks in different colors

- forest.netmeta():
- new argument ‘equal.size’ to determine whether square size should be equal or proportional to precision of estimates

- forest.netbind(), forest.netsplit():
- new default for argument ‘equal.size’, i.e., square sizes are equal

- forest.netbind():
- new argument ‘subset.treatments’ to select treatments shown in forest plot

- netmeasures():
- return direct evidence proportion for single design with two treatments

- netheat():
- all designs are shown in net heat plot by default

New internal function invmat() to calculate inverse of matrix

New internal function calcV() to calculate variance-covariance matrix used as input to rma.mv()

nma.ruecker(), multiarm():

- use solve() instead of ginv() to calculate inverse of matrix L

netmeta():

- new list element ‘comparisons’ with information on direct comparisons

netconnection():

- new list elements ‘comparisons’ and ‘subnet.comparisons’ with information on direct comparisons

netimpact():

- consider values for arguments ‘tol.multiarm’ and ‘tol.multiarm.se’ from network meta-analysis object

nma.krahn():

- new argument ‘reference.group’ to specify the reference group

Treatment labels can be rotated in network graphs

Additional checks whether net heat plot is feasible

Calculate direct evidence proportion and indirect treatment estimates for network meta-analyses created with netmetabin()

Network graph for objects created with netconnection(), netcomb() or discomb()

In summaries, print z- and p-values for network estimates if a reference group is defined

- netmetabin():
- not overall heterogeneity / inconsistency statistic calculated for Mantel-Haenszel method, but, the overall inconsistency statistic (treatment effects are aggregated within designs)

- decomp.design(), netheat():
- do not conduct decomposition of designs for objects created with netmetabin(); reported decomposition and net heat plot referred to reanalysis using netmeta()

- netmeasures():
- works for network meta-analyses created with netmetabin(); reported results referred to reanalysis using netmeta()

- netsplit():
- SIDDE method works for network meta-analysis created without argument ‘data’ or empty networks after dropping a design

- print.summary.netmeta():
- output states “test of heterogeneity” for a single design and “test of inconsistency” for Mantel-Haenszel method

- netrank():
- can be used with network meta-analysis object created with netcomb()

- netmeta():
- new argument ‘small.values’ passed on to netrank(), forest.netmeta() and netposet()

- netgraph.netmeta():
- new argument ‘srt.labels’ to rotate treatment labels

- plot.netrank():
- get rid of warnings ‘Undefined global functions or variables’

- netbind():
- argument ‘…’ can be a single list of network meta-analysis objects

- print.netmeta():
- new arguments ‘truncate’ and ‘text.truncate’ to only show selection of individual study results (useful for very long printouts or to only show individual results of multi-arm studies))
- print z- and p-values for tests of overall effect against a reference group (argument ‘reference.group’)

- print.netconnection():
- new argument ‘distance’ in order to print the distance matrix
- by default, do not print the distance matrix

- netsplit():
- new arguments ‘comb.fixed’, ‘comb.random’ and ‘backtransf’

Rename list elements starting with ‘zval.’ to ‘statistic.’

netcomb():

- export covariance matrices ‘Cov.fixed’ and ‘Cov.random’

netmeta(), netcomb():

- export study design for each pairwise comparison (list element ‘design’)

discomb():

- export study designs (list element ‘design’), list of designs (‘design’) and number of designs (‘d’)

Argument ‘single’ renamed to ‘length’ in calls of chkchar(), chkcolor(), chklevel() and chknumeric()

New internal function is.zero() to determine whether a small number is essentially zero (i.e., whether

*abs(x) < 10*.Machine$double.eps*)New internal function updateversion() to update older netmeta objects

New internal function designs() to determine study designs

New internal function netheat-internal() with auxiliary functions for netheat()

nma.ruecker(), nma.additive():

- use ginv() to calculate inverse of matrix L
- set small numbers which are essentially zero to zero in matrix Lstar

Function netimpact() can be used with network meta-analysis objects created with netmetabin()

No warning is printed that treatments within comparisons have been re-sorted in increasing order (which has been rather a note than a warning)

- netmetabin():
- bug fix for studies with 0 events and 0 participants

- discomb():
- return standard errors of individual studies in correct order (list element ‘seTE’)

- netbind():
- function can be used with network meta-analysis objects created with netmetabin()

- as.data.frame.netmeta():
- correct printout if number of studies is equal to the number of treatments to the power of 2

- summary.netmeta() exported

- netmeta(), discomb():
- do not print a warning / note that treatments within comparisons have been re-sorted in increasing order
- check whether all studies provide missing estimates and standard errors (and stop execution with an informative error message)

- netmeta(), netcomb(), discomb():
- export the design matrix (new list element ‘X.matrix’)

- discomb():
- export the number of subnetworks

- forest.netsplit():
- print an informative warning (instead of an obscure error message) if no comparison in the network provides the requested combination of direct and indirect evidence

- Use Markdown for NEWS

- prepare():
- call metagen() with argument ‘method.tau.ci = ""’ to suppress calculation of confidence interval for tau2

In multi-arm studies, negative weights (resulting from slightly inconsistent standard errors) contributing less than 0.1% to the weight of a study are set to 0

Separate consistency tolerances can be specified for treatment estimates and standard errors (which are consistent by design in multi-arm studies, however, can be inconsistent due to rounding of treatment estimates and standard errors)

New default for consistency tolerance: 0.001 instead of 0.0005

Print tau in addition to tau2 in outputs

Print confidence interval for I2 in outputs

- netmeta(), discomb():
- check for numeric values in arguments ‘TE’ and ‘seTE’
- new argument ‘tol.multiarm.se’ to check standard errors in multi-arm studies

- netmetabin():
- check for numeric values in arguments ‘event1’, ‘n1’, ‘event2’, and ‘n2’
- new argument ‘tol.multiarm.se’ to check standard errors in multi-arm studies

- print.summary.netmeta(), print.summary.netcomb():
- new argument ‘digits.tau’ to specify number of digits for tau
- new arguments ‘text.tau2’, ‘text.tau’, and ‘text.I2’ to change text printed to identify respective heterogeneity measure

- Revision of help page examples to reduce runtime below 5 seconds (CRAN requirement)

- multiarm():
- negative weights contributing less than 0.1% to the weight of a study are set to 0

- chkmultiarm():
- use same order of arguments as in netmeta()
- new argument ‘tol.multiarm.se’ to check standard errors

- nma.ruecker(), nma.additive():
- return lower and upper confidence limits for I2

New functions netimpact(), netgraph.netimpact(), print.netimpact() to measure the impact of individual studies to network estimates

New function plot.netrank() to produce image plot of P-scores

Equivalence limits can be added to forest plots

Use

**roxygen2**for development of R package**netmeta**

- netmeta():
- no error if argument ‘studlab’ is missing
- tackle numerical problems with zero treatment arm variances - actually by changes in internal function multiarm()
- calculate the correct number of patients and events for each treatment arm in networks with multi-arm studies

- netmetabin():
- only drop single treatment arms without any events in multi-arm studies instead of the complete design (which is the correct behaviour only for two-arm studies)
- keep the original design for multi-arm studies if a single treatment arm without any events has been dropped, e.g., the design X:Y:Z is not changed to X:Z if no events were observed in treatment arm Y in any multi-arm study
- no error if argument ‘event1’ is not an R object created with pairwise() and argument ‘data’ is not used
- no error in printing of network meta-analysis object if argument ‘event1’ is not an R object created with pairwise()
- calculate the correct number of patients and events for each treatment arm in networks with multi-arm studies

- netgraph():
- argument ‘seq’ equal to “optimal” works for a single design
- multi-arm studies are highlighted if argument ‘labels’ is used
- comparisons defined by argument ‘highlight’ are marked in the network graph if argument ‘labels’ is used

- pairwise():
- no error if function is used without argument ‘data’

netgraph() is a generic function and original function netgraph() renamed to netgraph.netmeta()

netgraph.netmeta():

- new argument ‘bg.points’
- new argument ‘scale.highlight’ which replaces argument ‘lwd.highlight’ (which actually was ignored)
- arguments ‘col.highlight’ and ‘scale.highlight’ can be vectors with same length as argument ‘highlight’
- print highlighted comparisons in the background of the graph

forest.netmeta():

- new argument ‘labels’ to provide treatment names - similar to netgraph()
- labels set automatically for columns “pscore”, “k” and “prop.direct” in argument ‘leftcols’ and ‘rightcols’

- multiarm():
- use ginv() to calculate inverse of matrix Lt
- set very small negative values in matrix W equal to zero
- object k instead of n denotes number of treatment arms (same notation as Rücker & Schwarzer, 2014)
- more liberal cutpoint to set negative variances to zero

- chkmultiarm():
- more liberal check for negative variances

- new auxiliary internal functions for forest plots

- Revision of help page examples
- to reflect changes in netmeta, versions 0.9-8 and 1.0-0
- to reduce runtime below 5 seconds (CRAN requirement)

Orestis Efthimiou oremiou@gmail.com is a new co-author of R package

**netmeta**New function netmetabin() for network meta-analysis of binary data using the Mantel-Haenszel method or the non-central hypergeometric distribution

New function funnel.netmeta() for ‘comparison-adjusted’ funnel plots

New function forest.netcomb() for forest plots of additive network meta-analysis

New functions netbind(), forest.netbind(), and print.netbind() to combine network meta-analysis objects and to generate a forest plot with results of several network meta-analyses

Separate Indirect from Direct Design Evidence (SIDDE) method implemented in netsplit()

All network comparisons can be included in a forest plot

Circular network graphs with minimal number of crossings available

Default setting for levels of confidence intervals can be specified using R function settings.meta(); the default is still 0.95, i.e., 95% confidence intervals are computed

New datasets: Gurusamy2011 and Dong2013

- netmeta():
- new list elements:
- ‘k.trts’ with number of studies evaluating a treatment
- ‘n.trts’ with number of observations receiving a treatment
- ‘events.trts’ with number of events observed for a treatment
- ‘n.matrix’ with number of observations in direct comparisons
- ‘events.matrix’ with number of events in direct comparisons
- ‘designs’ with treatment designs

- correct entry for list element ‘designs’ for single design
- only print information on studies with missing treatment effect or standard error if argument ‘warn’ is TRUE

- new list elements:
- pairwise():
- keep original order of studies
- arguments ‘event’ and ‘n’ can be used for generic meta-analysis method based on arguments ‘TE’ and ‘seTE’
- argument ‘n’ can be used for meta-analysis with count outcomes (based on arguments ‘event’ and ‘time’)
- infinite treatment estimates and standard errors set to NA
- by default, do not print warnings if comparisons will not be included in network meta-analysis

- netsplit():
- new argument ‘method’ to choose approach to split direct and indirect evidence

- forest.netmeta():
- argument ‘reference.group’ can be a vector in order to include several / all network comparisons in a forest plot
- (invisibly) returns a data frame with information used to produce the forest plot

- forest.netsplit() and print.netsplit():
- argument ‘showall’ replaced with ‘show’ (see help pages)

- forest.netsplit():
- show prediction intervals as colored bars
- forest plot with layout ‘subgroups by comparisons’: omit treatment estimates in rows with prediction intervals if network estimates are also shown

- netcomb() and discomb():
- argument ‘seq.components’ replaced with ‘seq.comps’

- discomb():
- arguments ‘reference.group’ and ‘baseline.reference’

- netposet():
- allow for ties in rankings

- netsplit():
- do not reorder a treatment comparison if reference treatment (argument ‘reference.group’) is part of a combined treatment, e.g., for reference.group = “A” and treatment comparison “A + B” vs “C”, the comparison will not be reordered as “C” vs “A + B”

- forest.netsplit():
- show correct prediction intervals

- netgraph():
- arguments ‘iterate’ and ‘allfigures’ ignored if argument ‘seq’ is equal to “optimal”

- netsplit():
- consider argument ‘digits’ for treatment estimates, i.e., do not always round to two digits

netmeta():

- keep original order of studies in list element ‘data’

netcomb() and discomb():

- check if argument ‘sep.components’ is a single character
- similar list elements as for R objects created with netmeta(); especially matrices with all network estimates added to output, see, for example, new list elements ‘TE.fixed’ and ‘TE.random’

Internal function nma.additive():

- calculate matrices with all network estimates

netleague() is a generic function

Help pages:

- examples added for forest.netsplit()

Main function netmeta():

- by default, results for fixed effects and random effects network meta-analysis are reported (only results for fixed effects model were reported in older versions)
- keep dataset used to conduct network meta-analysis
- number of events and number of observations can be provided (and are considered from R objects created with pairwise() function)

Function pairwise():

- all variables from the original dataset are kept in the output dataset

League tables

- show the direct treatment estimates from pairwise comparisons in the upper triangle if the table is created for a single network meta-analysis
- report pairwise comparisons of the treatment in the row versus the treatment in the column in the lower triangle and column versus row in the upper triangle (common presentation for network meta-analyses)

Network graphs are much more flexible, e.g., color of lines / edges can be specified for each direct pairwise comparison

New function discomb() for disconnected networks sharing at least one common treatment component to apply the additive network model for combinations of treatments

Treatment separator (argument ‘sep.trts’) can be special character from regular expressions

Between-study variance tau-squared is reported as NA instead of 0 in networks without heterogeneity / inconsistency

netmeta():

- settings for printing of results are defined by settings.meta(), i.e., new default is to print results for both fixed effects and random effects model
- new arguments ‘event1’, ‘event2’, ‘n1’, and ‘n2’ to provide number of events and observations for the two treatment groups
- new argument ‘keepdata’ to choose whether original dataset should be part of network meta-analysis object

- new list element ‘data’ to keep dataset used to conduct network meta-analysis (if argument ‘keepdata’ is TRUE)

netgraph():

- argument ‘col’ can be a matrix, e.g., created with netmatrix(), to specify the color of lines / edges for each direct pairwise comparison
- arguments ‘col.points’, ‘cex.points’, and ‘pch.points’ can be used to specify the color, size, and plotting symbol for each treatment separately
- new argument ‘adj’ to specify the adjustment of treatment labels
- new argument ‘pos.number.of.studies’ to specify the position of the number of treatments on the edges
- (invisibly) returns a list with information on nodes and edges (position, color, etc.) used to produce the network graph

pairwise():

- print correct labels in error message for studies with duplicate treatments

all variables from the original dataset are kept in the output dataset

print.netmeta():

print uniquely abbreviated treatment names

netconnection() and print.netconnection():

- new argument ‘sep.trts’ to print abbreviated treatment names

netleague():

- new argument ‘big.mark’ to specify character printed as thousands separator, e.g., big.mark = “,” will result in printing of 1,000 for the number 1000
- new argument ‘text.NA’ to label missing values, i.e., for pairwise comparisons without direct evidence
- new argument ‘direct’ to print direct treatment estimates (if argument ‘y’ is not missing)

print.netsplit():

- new argument ‘legend’ to suppress printing of the legend

print.summary.netcomb():

- new arguments ‘digits.tau2’ and ‘digits.I2’

New auxiliary function netmatrix() to create a matrix with additional information for pairwise comparisons (e.g., risk of bias assessment)

- netmeta():
- list elements ‘P.fixed’ and ‘P.random’ contained wrong values for network meta-analyses with a single design which resulted in an error using forest.netmeta()

- netcomb():
- use correct between-study variance in random effects additive network meta-analysis model
- use correct order of studies to calculate treatment estimates
- can be used with single pairwise comparison

- print.summary.netcomb():
- use correct (abbreviated) names for treatment components

new internal functions compmatch() and compsplit() for argument ‘sep.trts’ taking special character from regular expression into account, e.g., sep.trts = “.”

new internal functions bySummary() which is used in netmeta(), netmatrix(), and pairwise()

createC() can be used with netconnection() objects (for disconnected networks)

netcomb.netmeta() has been renamed to netcomb()

netmeta():

- report I2 as value between 0 and 1 (instead of 0 and 100)
- new list element ‘trts’ (character vector with treatment names)

Internal function nma.ruecker():

- use internal function isquared() from package
**meta**to calculate I2

- use internal function isquared() from package
Internal function nma.additive():

- calcuate between-study variance tau2 and heterogeneity statistic I2

Internal function prcombs():

- new argument ‘seq’ to order treatments

Version of R package

**meta**must be larger or equal 4.9-0New function to produce forest plots with network, direct, and indirect evidence

New function to estimate additive network meta-analysis for combinations of treatments

New default in function netsplit(): treatment comparisons are selected from upper treatment estimates matrix, i.e., comparisons are “A vs B”, “A vs C”, and “B vs C” for treatments “A”, “B”, and “C” instead of “B vs A”, etc.

Zero treatment arm variance in multi-arm studies results in a warning instead of an error message

League tables can be exported as CSV or Excel file

New argument ‘backtransf’ indicating whether estimates should be back-transformed in printouts and plots, e.g., to show results as odds ratios instead of log odds ratios

P-values can be printed in scientific notation

P-values equal to 0 are actually printed as “0” instead of “< 0.0001”

Thousands separator can be used in printouts and forest plots for large numbers

- new functions:
- forest.netsplit() to produce forest plots with direct and indirect evidence
- print.netleague() to print league table
- treats() to create uniquely abbreviated treatment names
- netcomb() and netcomb.netmeta() to estimate additive network meta-analysis models for combinations of treatments

- summary.netcomb(), print.netcomb(), and print.summary.netcomb() to print (summaries of) netcomb objects

- print.decomp.design(), print.netmeta(), print.netsplit(), and print.summary.netmeta():
- new argument ‘big.mark’ to specify character printed as thousands separator, e.g., big.mark = “,” will result in printing of 1,000 for the number 1000
- new argument ‘scientific.pval’ to print p-values in scientific notation, e.g., 1.2345e-01 instead of 0.12345

- netmeta():
- new argument ‘backtransf’ (see above)
- new argument ‘nchar.trts’ to abbreviate treatment names in printouts

- netleague():
- function does not print league table, but only generates it (necessary for export of league table)
- new arguments ‘bracket’ and ‘separator’ to define layout of confidence intervals (see R function cilayout() from R package
**meta**)

- netsplit():
- new argument ‘upper’ to specify whether lower or upper triangle of treatment estimate matrix should be used to build comparisons
- column with comparisons added to data frames with network, direct, and indirect estimates
- additional new arguments (see help file): ‘reference.group’, ‘baseline.reference’, ‘sep.trts’, ‘quote’

- netmeasures():
- do not round results to four digits

- print.netmeta(), print.summary.netmeta():
- new arguments ‘backtransf’ and ‘nchar.trts’ (see above)
- argument ‘logscale’ removed (replaced by argument ‘backtransf’)

- Dataset Senn2013:
- new columns ‘treat1.long’ and ‘treat2.long’ with full treatment names added

- Help pages:
- new help pages for forest.netsplit(), print.netleague(), and treats()
- updated help pages for netposet() and netsplit()

- netsplit():
- order of treatments in printouts corresponds to treatment comparison, e.g., “A:B” means that treatment “A” was compared with treatment “B” (and not the other way around). Side note, not sure whether this is a bug or a feature as “A:B” noted the design “comparison A and B” so far.

- netposet():
- function works with a ranking matrix that contains missing elements, i.e., rankings that do not include all treatments

- netgraph():
- areas for multi-arm studies are printed at the correct locations if argument ‘start.layout’ is not equal to “circle” and argument ‘seq’ defines a specific treatment order (this bug was introduced in netmeta, version 0.7-0)

chkmultiarm():

- warning for zero treatment arm variance instead of an error

new internal function uppertri() to extract elements from the upper triangle of a matrix

new internal function treats() to abbreviate treatment names

new internal function nma.additive() for estimation of additive network meta-analysis models

new internal function createC() to create C matrix used as input to nma.additive()

new internal functions prcombs() and prcomps() for printing of netcomb objects

Internal function p.ci() replaced with formatCI() from R package

**meta**Internal function format.TE() replaced with formatN() from R package

**meta**

Prediction intervals can be calculated for treatment estimates from a network meta-analysis

In netmeta(), Q statistics for heterogeneity and design inconsistency are calculated according to Krahn et al. (2013); see help page of decomp.design()

In printouts and forest plots, the reference treatment can be considered as treatment of interest or comparator (default), i.e., either comparisons of reference vs other treatments or other treatments vs reference are reported

Tests for heterogeneity and design inconsistency are shown in printouts

A biplot can be generated to show partial ordering of treatment rankings for more than two outcomes

Additional checks implemented for multi-arm studies:

- negative or zero treatment arm variances
- duplicate treatment comparisons or incomplete sets of treatment comparisons within a study

- netmeta():
- new arguments ‘prediction’ and ‘level.predict’ to calculate prediction intervals
- list elements ‘Q.heterogeneity’ and ‘Q.inconsistency’ based on Krahn et al. (2013)
- new list elements ‘prediction’, ‘lower.predict’, ‘upper.predict’, ‘df.Q.heterogeneity’, ‘pval.Q.heterogeneity’,‘df.Q.inconsistency’, and ‘pval.Q.inconsistency’
- list element ‘df’ renamed to ‘df.Q’
- stop with an informative error message if (i) any treatment arm variance derived from the treatment comparison variances is negative or zero, or (ii) in case of duplicate comparisons or an incomplete set of treatment comparisons within a study
- argument ‘details.tol.multiarm’ renamed to ‘details.chkmultiarm’

- netmeta(), forest.netmeta(), print.netmeta(), print.summary.netmeta(), and summary.netmeta():
- new argument ‘baseline.reference’ to print results for comparisons between reference and other treatments, or vice versa

- print.netmeta(), print.summary.netmeta(), and summary.netmeta():
- new argument ‘prediction’ to print prediction intervals

- print.summary.netmeta():
- print information on tests for overall heterogeneity and inconsistency

- summary.netmeta():
- arguments ‘level’ and ‘level.comb’ removed from R function (i.e., one has to re-run the netmeta() command for confidence intervals with other coverage levels)

- plot.netposet():
- new argument ‘plottype’ to choose between scatter plot or biplot
- new arguments to modify layout (‘cex.text’, ‘col.text’, pch, cex.points, col.points)

- decomp.design() and netmeasures():
- new argument ‘warn’ to suppress printing of warnings

New internal function upgradenetmeta() to add missing list elements to older netmeta objects

R function ci() from R package

**meta**added to NAMESPACEchkmultiarm():

- additional checks for (i) negative and zero variances as well as
- duplicate treatment comparisons or incomplete sets of treatment comparisons within a study

- additional checks for (i) negative and zero variances as well as

New function netleague() to print league table with network meta-analysis results

pairwise():

- zero events for binary outcomes or incidence rates are handled correctly in multi-arm studies by adding an increment to all treatment arms (in older versions of netmeta inconsistent treatment effects for multi-arm studies were possible as increments were considered in individual comparisons instead of all comparisons for a multi-arm study)
- print warning and information on treatment comparisons with missing treatment estimate or standard error

forest.netmeta():

- reference group can be omitted from forest plot
- treatments can be sorted by treatment estimate (TE), standard error (seTE), number of studies in direct comparison (k), and proportion of direct information (prop.direct)

netmeta():

- additional checks for correct number of comparisons in multi-arm studies and more informative error message for uncorrect number of comparisons in multi-arm studies due to missing treatment effects or standard errors in single comparisons
- separator used in comparison names to concatenate treatment labels can be specified by user (default: “:”)

In decomp.design(), by default, only print designs contributing to design-specific decomposition of within-designs Q statistic

Input to netdistance() can be either a netmeta object or a matrix

- forest.netmeta():
- new argument ‘drop.reference.group’
- argument ‘sortvar’ can be used in the following ways: sortvar = TE, sortvar = -TE, sortvar = seTE, sortvar = -seTE, sortvar = k, sortvar = -k, sortvar = prop.direct, sortvar = -prop.direct

- print.decomp.design() and netheat():
- new argument ‘showall’ which defaults to FALSE

- print.summary.netmeta():
- print number of designs
- print preset between-study variance and corresponding information if argument ‘tau.preset’ is not NULL in netmeta()

- pairwise():
- in multi-arm studies exclude comparisons with missing sample size or standard error from calculation of pooled variance for standardized mean difference (sm = “SMD”)

- plot.netposet():
- new default for argument ‘arrows’, i.e., by default, do not show arrows in scatter plot

- print.netsplit():
- number of studies providing direct evidence printed

- netdistance():
- argument name changed from ‘A’ to ‘x’ in order to reflect that input of R function can be either a netmeta object or an adjacency matrix

- Help pages:
- examples corrected for dataset dietaryfat
- do not run all examples in forest.netmeta() as CRAN only allows a run time below 10 seconds for examples provided on a help page
- R code to produce forest plot added to examples in dataset Wood2010

netmeta():

- new list element ‘d’ with number of designs
- new list element ‘B.matrix’ with the edge-vertex incidence matrix

summary.netmeta():

- new list element ‘d’ with number of designs
- new list element ‘tau.preset’

netsplit():

- new list element ‘k’ with number of studies providing direct evidence

netconnection():

- argument checks added
- better code documentation

Internal function decomp.tau():

- detach all designs (including protuding edges)

New internal function createB() to calculate edge-vertex incidence matrix

netmeta(), netconnection(), multiarm(), and chkmultiarm():

- use internal function createB() instead of dedicated R code

print.summary.netmeta(), nma.ruecker(), and decomp.tau():

- use command pchisq(…, lower.tail = FALSE) instead of 1 - pchisq(…)

netsplit() used wrong comparison labels if argument ‘reference.group’ was used in netmeta()

netmeasures() ignores value of argument ‘reference.group’ in netmeta object

Calculate indirect treatment estimates based on direct evidence proportion

Ranking of treatments based on fixed effect model added to netrank()

New function netsplit() to split direct and indirect evidence

New functions netposet(), print.netposet(), and plot.netposet() to calculate, print and plot partial ordering of rankings

New function hasse() to draw Hasse diagram of partially ordered treatment rankings

netmeta():

- can be used with R objects created with pairwise()
- checks for consistency of treatment effects and variances in multi-arm studies

Import ginv() from R package

**MASS**(for consistency checks)Suggested packages added (for Hasse diagram):

**hasseDiagram**and**grid**Bug fixes:

- netmeta() calculates correct direct evidence estimates under random effects model (list components ‘TE.direct.random’, ‘seTE.direct.random’, …, ‘pval.direct.random’); so far results from fixed effect model have been used
- netmeta() excludes a treatment from list component ‘seq’ if all comparisons containing the respecitve treatment are excluded due to missing values in treatment effect or standard error
- netmeasures() does not result in an error if no or only one study with two treatments is available

New arguments random and tau.preset in netmeasures()

New functions netsplit() and print.netsplit()

Consider ordering of treatments in netrank() which is defined by argument seq in netmeta()

For multi-arm studoes, calculate pooled standard deviation in pairwise() if means and standard deviations are provided and summary measure is equal to “SMD”

netmeta():

- new list element ‘k.direct’ with number of studies in meta-analyses with direct evidence

nma.ruecker():

- bug fix such that estimates from random effects model are used for direct treatment estimates if argument ‘tau.direct’ is larger than zero

nma.krahn():

- bug fix such that use of function does not result in an error if either no or only one study with two treatments is available

pairwise():

- data.frame commands use argument stringsAsFactors = FALSE

chkmultiarm(): new internal function to check consistency of treatment effects and variances in multi-arm studies; calls ginv() from MASS library

new internal function lowertri() to extract elements from the lower triangle of a matrix

- R package
**rgl**moved from imported to suggested packages as- 3-D network plots are not essential for network meta-analysis
- installation of
**netmeta**breaks under macOS if XQuartz is not available

- Help page of netgraph() updated (information on
**rgl**package)

- Use chkclass() from
**meta**package to check for class membership

Number of studies can be added to network graph

Distance matrix can be provided directly to generate network graph

shadowtext() from

**TeachingDemos**package by Greg Snow added to**netmeta**packageP-scores can be printed in forest plot

help page with brief overview of

**netmeta**package addednetgraph():

- new arguments to add number of studies to network graph (number.of.studies, cex.number.of.studies, col.number.of.studies, bg.number.of.studies)

- plastic look retained for highlighted comparisons
- new argument D.matrix to provide treatment distances directly

- new arguments to add number of studies to network graph (number.of.studies, cex.number.of.studies, col.number.of.studies, bg.number.of.studies)
netmeta():

- function can be used with a single pairwise comparison without resulting in an error

forest.netmeta():

- argument sortvar can be equal to Pscore, “Pscore”, -Pscore, or “-Pscore” to sort treatments according to ranking generated by netrank()
- argument leftcols or rightcols can include “Pscore” to add a column with P-Scores to the forest plot
- new arguments small.values and digits.Pscore for P-Scores

print.netmeta():

- use correct layout for network meta-analysis with a single pairwise comparison

decomp.design(), netheat(), netmeasures():

- print a warning and return NULL for network meta-analysis with a single design

netconnection():

- print sensible error message if argument treat2 is missing or of different length than argument treat 1

netdistance():

- print sensible error message if argument A is not a matrix

Help pages updated: decomp.design(), print.decomp.design(), netgraph(), netheat(), netmeasures()

- New function:
- shadowtext() to print number of studies

- nma.ruecker():
- keep dimension of matrices W and B.matrix for network meta-analysis with a single pairwise comparison

- nma.krahn():
- print a warning and return NULL for network meta-analysis with a single design

- decomp.tau(), tau.within():
- return NULL for network meta-analysis with a single design

New functions:

- netdistance (calculate distance matrix; replacement for internal function nodedist)
- netconnection (Get connectivity information for network)
- print.netconnection (corresponding print function)

Internal function nodedist removed (replaced by netdistance function)

Import functions from R package

**rgl**(for 3-D plots)New dataset Woods2010 (use long format in pairwise function)

Function netmeta:

- check connectivity of network and stop with informative error message if network is not fully connected
- new list components: ‘Cov.fixed’ (variance-covariance matrix for fixed effect model) ‘Cov.random’ (variance-covariance matrix for random effects model)

Function pairwise:

- extension to long data format (see example on help page)

Function netmeta:

- new arguments ‘dim’, ‘eig3’, and ‘zpos’ to generate 3-D network plots

Function stress (used internally):

- extension to generate 3-D network plots
- use netdistance function instead of nodedist

Function nma.ruecker (used internally):

- use of netmeta function does not result in an error for networks without heterogeneity / inconsistency, i.e. networks with zero degrees of freedom (e.g. a star-shaped network with only a single study for each comparison; simple example: single comparisons A-B, A-C, A-D)
- calculate variance-covariance matrix

Function print.netrank:

- print title of meta-analysis (if available)

Function print.summary.netmeta:

- print “–” instead of “< 0.0001” in networks without heterogeneity / inconsistency
- print “0” instead of “< 0.0001” if tau-squared is zero
- print ‘p-value’ instead of ‘p.value’

Function print.decomp.design:

- print ‘p-value’ instead of ‘p.value’

Help page of netmeta function:

- more details on contrast- and arm-based data format
- reference to book “Meta-Analysis with R” and Rücker & Schwarzer (2014) added
- add information that hazard ratio is a possible summary measure
- change error in description of adjustment in random effects model

Help page of netgraph function:

- example for 3-D network plot added

Help page of netrank function:

- reference to Rücker & Schwarzer (2015) updated

Help page of pairwise function:

- description on use of long data format added
- more information on additional arguments for meta-analysis functions

New help pages:

- netconnection, print.netconnection
- netdistance
- Wooks2010 dataset

- New functions netrank and print.netrank:
- frequentist method to rank treatments in network

- Function netmeta:
- print less irritating warning if treatment comparisons are resorted (as this is more a note than a warning)

- Function print.netmeta:
- minor change in printout (old: “Data utilised in network meta-analysis …”; new: “Results …”)

- Help pages:
- new help page for netrank function
- reference Rücker & Schwarzer (2015) added in help page of netgraph function
- link to pairwise function added in help page of netmeta function

Version of R package

**meta**must be larger or equal 4.0-0Title of R package changed

New function pairwise:

- transforms data that are given in an arm-based format (e.g. input for WinBUGS is of this format) to contrast-based format that can be read by function netmeta

New datasets:

- dietaryfat (dataset with incidence rates as outcomes)
- parkinson (continuous outcomes)
- smokingcessation (binary outcomes)

Function netmeta:

- implement a general check for correct number of comparisons for multi-arm studies
- use setseq function to check and set value of argument ‘seq’
- use setref function to check and set value of argument ‘reference.group’
- use chklevel function from R package
**meta**to check levels of confidence intervals - consider attribute ‘sm’ from R objects generated with R function pairwise
- function can be used for a pairwise meta-analysis (bug fix in nma.ruecker function used internally)

Function netgraph:

- check that matrix ‘thickness’ (if provided) has same row and column names as argument ‘labels’
- use setseq function to check and set value of argument ‘seq’
- stop with an error message if argument ‘seq’ or ‘labels’ is NULL

Function netheat:

- no net heat plot produced if (i) the number of designs is equal or smaller than 2 or (ii) no between-design heterogeneity exists
- unintentional warnings omitted

Function forest.netmeta:

- print a warning that the first treatment is used as reference if the reference group is unspecified instead of producing an error
- use setseq function to check and set value of argument ‘seq’
- use setref function to check and set value of argument ‘reference.group’

Function print.summary.netmeta:

- print “.” instead of “0” or “1” for diagonal elements of treatment effect and confidence interval matrices
- print “.” instead of “0” or “1” for reference group (if provided)
- use setref function to check and set value of argument ‘reference.group’
- use is.relative.effect function from R package
**meta**to check if a relative effect measure is used (argument ‘sm’)

Function print.netmeta:

- use setref function to check and set value of argument ‘reference.group’
- use is.relative.effect function from R package
**meta**to check if a relative effect measure is used (argument ‘sm’)

Function summary.netmeta:

- use setref function to check and set value of argument ‘reference.group’

Function decomp.tau and tau.within (used internally):

- bug fix such that no error is produced in decomp.design and netheat function for networks without heterogeneity and inconsistency

Function print.decomp.design:

- omit printing of information on between-designs Q statistic after detaching of single designs if no between-design heterogeneity exists
- use format.tau function from R package
**meta**to print “0” instead of “< 0.0001” if tau-squared is zero

New functions (used internally):

- setseq - check and set argument ‘seq’ (and argument ‘sortvar’ in forest.meta function)
- setref - check and set argument ‘reference.group’
- chklist - check for a list

New help pages for function pairwise and datasets dietaryfat, parkinson, and smokingcessation.

- Function netgraph:
- complete rewrite of this function (without changing previous default settings substantially)
- list of major new features:
- additional layouts beside circular presentation (see argument ‘start.layout’)
- implementation of stress majorization algorithm to optimize layout (argument ‘iterate’)
- additional methods to determine width of lines connecting treatments (argument ‘thickness’)
- highlight multi-arm studies (arguments ‘multiarm’ and ‘col.multiarm’)
- possibility to provide a neighborhood matrix to specify neighborhood differently than using the adjacency matrix, for example content-based (argument ‘N.matrix’)
- possibility to provide x- and y-coordinates for network plot (arguments ‘xpos’ and ‘ypos’)

- Function netmeta:
- calculate treatment estimates from all direct pairwise treatment comparisons (both fixed effect and random effects model)
- new list components: ‘tau.preset’, ‘TE.direct.fixed’, ‘seTE.direct.fixed’, ‘lower.direct.fixed’, ‘upper.direct.fixed’, ‘zval.direct.fixed’, ‘pval.direct.fixed’, ‘TE.direct.random’, ‘seTE.direct.random’, ‘lower.direct.random’, ‘upper.direct.random’, ‘zval.direct.random’, ‘pval.direct.random’

- Function nma.ruecker (used internally)
- changed accordingly to reflect changes in netmeta function

- Function forest.netmeta:
- new argument sortvar (default: sort treatment effect estimates according to list component ‘seq’ of netmeta object)

- New functions stress and nodedist (used internally)
- auxiliary functions for netgraph function

- Help pages updated accordingly

Functions nma.krahn, netmeasures, netheat, decomp.design, and print.decomp.design:

- random effects network meta-analysis added

Function netheat:

- new argument ‘random’

Functions nma.krahn, decomp.design, and netheat:

- new argument ‘tau.preset’

Function decomp.design:

- correct design-specific decomposition of Q statistic in network meta-analysis with multi-arm studies
- list component ‘Q.design’ renamed to ‘Q.het.design’
- list component ‘Q.detach’ renamed to ‘Q.inc.detach’
- list component ‘residuals’ renamed to ‘residuals.inc.detach’
- new list components: ‘Q.inc.random’, ‘Q.inc.random.preset’, ‘Q.inc.design.random.preset’, ‘residuals.inc.detach.random.preset’, ‘tau.preset’

New functions tau.within and decomp.tau (used internally)

Help pages updated accordingly

- Functions netmeta and nma.ruecker:
- modified such that the estimated tau-squared in random effects model considers multi-arm studies

- Function print.netmeta:
- information on percentage weight not printed as interpretation is difficult

- Dataset Senn2013:
- use of unpooled standard error for each treatment comparison

- Function netmeta:
- numeric values for arguments ‘treat1’ and ‘treat2’ not converted to character values (only factors converted to characters)
- check whether treatments are different (arguments ‘treat1’ and ‘treat2’)

- Function print.summary.netmeta:
- print random effects estimates according to argument ‘seq’

- Function forest.netmeta:
- sort treatment effect estimates according to argument ‘seq’

- Function nma.ruecker (used internally):
- changed such that all treatment effects are calculated irregardless of treatment order (some treatment effects remained NA depending on order of treatments)

- Function netmeasures:
- bug fix using correct formula to calculate direct evidence proportion (variance instead of standard error)

Function netmeta:

- argument ‘seq’ added (see also R function netgraph)

Function netgraph:

- new default for argument ‘seq’

Help pages updated accordingly

Some internal code cleaning to improve readability of R functions

New functions added:

- netgraph (network graph)
- netheat (net heat graph)
- netmeasures (measures for network meta-analysis)
- decomp.design (design-based decomposition of Cochran’s Q)
- print.decomp.design (corresponding print function)
- p.ci, format.TE, nma.krahn, nma.ruecker (used internally)

Function netmeta:

- Check added whether all pairwise comparisons are provided for multi-arm studies

Help pages added for new functions

Help page of function netmeta updated

- Functions netmeta and summary.netmeta:
- new list component ‘n’ (number of treatments)

- Function print.summary.netmeta:
- modified such that number of treatments is printed
- modified such that argument ‘reference.group’ works as expected for random effects model

- First version released on CRAN