The tipmap-package facilitates the planning and analysis of partial extrapolation studies in pediatric drug development. It provides an implementation of a Bayesian tipping point approach that can be used in analyses based on robust meta-analytic predictive (MAP) priors. Further functions facilitate expert elicitation of a primary (pre-specified) weight of the informative component of the MAP prior and the computation of operating characteristics.

Installation

CRAN

You can install the current stable version from CRAN with:

install.packages("tipmap")

GitHub

You can install the current development version from GitHub with:

if (!require("remotes")) {install.packages("remotes")}
remotes::install_github("Boehringer-Ingelheim/tipmap")

Getting started

Load the package:

library(tipmap)

The prior data (collected in the source population):

prior_data <- create_prior_data(
  n_total = c(160, 240, 320),
  est = c(1.23, 1.40, 1.51),
  se = c(0.4, 0.36, 0.31)
)

The data from the new trial (collected in the target population):

ped_trial <- create_new_trial_data(
  n_total = 30,
  est = 1.27,
  se = 0.95
)

Derivation of the meta-analytic predictive (MAP) prior:

uisd <- sqrt(ped_trial["n_total"]) * ped_trial["se"]
g_map <-
  RBesT::gMAP(
    formula = cbind(est, se) ~ 1 | study_label,
    data = prior_data,
    family = gaussian,
    weights = n_total,
    tau.dist = "HalfNormal",
    tau.prior = cbind(0, uisd / 16),
    beta.prior = cbind(0, uisd)
  )

map_prior <- RBesT::automixfit(
  sample = g_map,
  Nc = seq(1, 4),
  k = 6,
  thresh = -Inf
)

Computing the posterior distribution for weights of the informative component of the MAP prior ranging from 0 to 1:

posterior <- create_posterior_data(
  map_prior = map_prior,
  new_trial_data = ped_trial,
  sigma = uisd)

Creating data for a tipping point analysis (tipping point plot):

tipmap_data <- create_tipmap_data(
  new_trial_data = ped_trial,
  posterior = posterior,
  map_prior = map_prior)

Create tipping point plot:

tipmap_plot(tipmap_data = tipmap_data)

Get tipping points:

get_tipping_points(
  tipmap_data,
  quantile = c(0.025, 0.05, 0.1, 0.2),
  null_effect = 0.1)

Citing tipmap

To cite tipmap in publications please use: Christian Stock and Morten Dreher (2023). tipmap: Tipping Point Analysis for Bayesian Dynamic Borrowing. R package version 0.5.2. URL: https://CRAN.R-project.org/package=tipmap