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MBNMAdose 0.4.1

The goal of MBNMAdose is to provide a collection of useful commands that allow users to run dose-response Model-Based Network Meta-Analyses (MBNMA). This allows evidence synthesis of studies that compare multiple doses of different agents in a way that can account for the dose-response relationship.

Whilst making use of all the available evidence in a statistically robust and biologically plausible framework, this also can help connect networks at the agent level that may otherwise be disconnected at the dose/treatment level, and help improve precision of estimates(Pedder et al. 2021). It avoids “lumping” of doses that is often done in standard Network Meta-Analysis (NMA). All models and analyses are implemented in a Bayesian framework, following an extension of the standard NMA methodology presented by (Lu and Ades 2004) and are run in JAGS (Just Another Gibbs Sampler). For full details of dose-response MBNMA methodology see Mawdsley et al. (2016). Throughout this package we refer to a treatment as a specific dose or a specific agent.

A short introductory YouTube video from the ESMAR Conference 2021 can be found here

Installation

On CRAN you can easily install the current release version of MBNMAdose from CRAN with:

install.packages("MBNMAdose")

For the development version the package can be installed directly from GitHub using the devtools R package:

# First install devtools
install.packages("devtools")

# Then install MBNMAdose directly from GitHub
devtools::install_github("hugaped/MBNMAdose")

Workflow

Functions within MBNMAdose follow a clear pattern of use:

  1. Load your data into the correct format using mbnma.network() and explore potential relationships
  2. Perform a dose-response MBNMA using mbnma.run(). Modelling of effect modifying covariates is also possibly using Network Meta-Regression.
  3. Test for consistency at the treatment-level using functions like nma.nodesplit() and nma.run()
  4. Examine model outputs, such as relative effects, forest plots and treatment rankings
  5. Use your model to predict responses using predict()

At each of these stages there are a number of informative plots that can be generated to help understand the data and to make decisions regarding model fitting. Exported functions in the package are connected like so:

MBNMAdose package structure: Light green nodes represent classes and the generic functions that can be applied to them. Dashed boxes indicate functions that can be applied to objects of specific classes

References

Lu, G., and A. E. Ades. 2004. “Combination of Direct and Indirect Evidence in Mixed Treatment Comparisons.” Journal Article. Stat Med 23 (20): 3105–24. https://doi.org/10.1002/sim.1875.

Mawdsley, D., M. Bennetts, S. Dias, M. Boucher, and N. J. Welton. 2016. “Model-Based Network Meta-Analysis: A Framework for Evidence Synthesis of Clinical Trial Data.” Journal Article. CPT Pharmacometrics Syst Pharmacol 5 (8): 393–401. https://doi.org/10.1002/psp4.12091.

Pedder, H., S. Dias, M. Bennetts, M. Boucher, and N. J. Welton. 2021. “Joining the Dots: Linking Disconnected Networks of Evidence Using Dose-Response Model-Based Network Meta-Analysis.” Journal Article. Medical Decision Making 41 (2): 194–208.

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Version

Install

install.packages('MBNMAdose')

Monthly Downloads

385

Version

0.4.3

License

GPL-3

Maintainer

Hugo Pedder

Last Published

April 18th, 2024

Functions in MBNMAdose (0.4.3)

dnonparam

Non-parameteric dose-response functions
dfpoly

Fractional polynomial dose-response function
devplot

Plot deviance contributions from an MBNMA model
getjagsdata

Prepares data for JAGS
get.prior

Get current priors from JAGS model code
get.relative

Calculates league table of effects between treatments in MBNMA and/or NMA models
genspline

Generates spline basis matrices for fitting to dose-response function
gen.parameters.to.save

Automatically generate parameters to save for a dose-response MBNMA model
duser

User-defined dose-response function
fitplot

Plot fitted values from MBNMA model
gout

Studies of treatments for Serum Uric Acid reduction in patients with gout
dspline

Spline dose-response functions
drop.disconnected

Drop studies that are not connected to the network reference treatment
mbnma.run

Run MBNMA dose-response models
mbnma.validate.data

Validates that a dataset fulfills requirements for MBNMA
nma.nodesplit

Node-splitting model for testing consistency at the treatment-level
inconsistency.loops

Identify comparisons in loops that fulfill criteria for node-splitting
plot.mbnma.network

Create an mbnma.network object
mbnma.update

Update MBNMA to monitor deviance nodes in the model
mbnma.nodesplit

Node-splitting model for testing consistency at the treatment level using MBNMA
mbnma.write

Write MBNMA dose-response model JAGS code
plot.nma

Run an NMA model
mbnma.comparisons

Identify unique comparisons within a network
print.mbnma.network

Print mbnma.network information to the console
pDcalc

Calculate plugin pD from a JAGS model with univariate likelihood for studies with repeated measurements
print.mbnma.predict

Print summary information from an mbnma.predict object
plot.mbnma

Forest plot for results from dose-response MBNMA models
osteopain

Studies of treatments for pain relief in patients with osteoarthritis
norm2lnorm

Convert normal distribution parameters to corresponding log-normal distribution parameters
psoriasis90

Studies of biologics for treatment of moderate-to-severe psoriasis (>=90% improvement)
rank

Set rank as a method
plot.mbnma.rank

Plot histograms of rankings from MBNMA models
predict.mbnma

Predict responses for different doses of agents in a given population based on MBNMA dose-response models
print.nodesplit

Prints summary results from a nodesplit object
psoriasis100

Studies of biologics for treatment of moderate-to-severe psoriasis (100% improvement)
psoriasis75

Studies of biologics for treatment of moderate-to-severe psoriasis (>=75% improvement)
print.relative.array

Print posterior medians (95% credible intervals) for table of relative effects/mean differences between treatments/classes
print.mbnma.rank

Prints summary information about an mbnma.rank object
print.nma.nodesplit

Prints summary results from an nma.nodesplit object
ssi_closure

Studies of wound closure methods to reduce Surgical Site Infections (SSI)
%>%

Pipe operator
recode.agent

Assigns agent or class variables numeric identifiers
rank.relative.array

Rank relative effects obtained between specific doses
ssri

Studies of Selective Serotonin Reuptake Inhibitors (SSRIs) for major depression
rank.mbnma

Rank parameter estimates
summary.mbnma.rank

Generates summary data frames for an mbnma.rank object
summary.mbnma.predict

Produces a summary data frame from an mbnma.predict object
plot.mbnma.predict

Plots predicted responses from a dose-response MBNMA model
rank.mbnma.predict

Rank predicted doses of different agents
triptans

Studies of triptans for headache pain relief
rescale.link

Rescale data depending on the link function provided
ref.synth

Synthesise single arm dose = 0 / placebo studies to estimate E0
summary.mbnma

Print summary of MBNMA results to the console
summary.mbnma.network

Print summary mbnma.network information to the console
summary.nodesplit

Generates a summary data frame for nodesplit objects
summary.nma.nodesplit

Generates a summary data frame for nma.nodesplit objects
check.network

Check if all nodes in the network are connected (identical to function in MBNMAtime)
default.priors

Sets default priors for JAGS model code
MBNMAdose-package

MBNMAdose for dose-response Model-Based Network Meta-Analysis
calc.edx

Calculates values for EDx from an Emax model, the dose at which x% of the maximal response (Emax) is reached
cumrank

Plot cumulative ranking curves from MBNMA models
changepd

Update model fit statistics depending on calculation for pD
DR.comparisons

Adds placebo comparisons for dose-response relationship
demax

Emax dose-response function
add_index

Add arm indices and agent identifiers to a dataset
dexp

Exponential dose-response function
devdev

Dev-dev plot for comparing deviance contributions from two models
dpoly

Polynomial dose-response function
dloglin

Log-linear (exponential) dose-response function
ditp

Integrated Two-Component Prediction (ITP) function
dmulti

Agent-specific dose-response function
alog_pcfb

Studies of alogliptin for lowering blood glucose concentration in patients with type II diabetes
drop.comp

Drop treatments from multi-arm (>2) studies for node-splitting