README.md

In Sterniii3/drugdevelopR: Utility-Based Optimal Phase II/III Drug Development Planning

drugdevelopR: Utility-based optimal phase II/III drug development planning.

The drugdevelopR package enables you to plan phase II/III drug development programs with optimal sample size allocation and go/no-go decision rules. The assumed true treatment effects can be fixed or modelled by a prior distribution. The corresponding R Shiny application has a graphic user interface and thus makes it accessible for users without prior knowledge of R. Fast computing is made possible by parallel programming. Theoretical foundations for this package were laid in the dissertation “Integrated Planning of Pilot and Subsequent Confirmatory Study in Clinical Research – Finding Optimal Designs in a Utility-Based Framework” by Stella Erdmann at the Institute of Medical Biometry at the University of Heidelberg.

On the package webpage, we supply full documentation of all functions as well as a tutorial for getting started with drugdevelopR.

Installation

Install the development version of the package directly from GitHub using the following code:

if(!require(devtools)) { install.packages("devtools"); require(devtools)} 
devtools::install_github("Sterniii3/drugdevelopR")

and access the drugdevelopR App via https://web.imbi.uni-heidelberg.de/drugdevelopR/.

Usage

Here is a basic example for applying drugdevelopR to a drug development program with a normally distributed outcome:

library(drugdevelopR)
#> Lade nötiges Paket: doParallel
#> Lade nötiges Paket: foreach
#> Lade nötiges Paket: iterators
#> Lade nötiges Paket: parallel
#> Lade nötiges Paket: progressr
# Optimize
optimal_normal(Delta1 = 0.625, Delta2 = 0.8, fixed = FALSE, # treatment effect
               n2min = 20, n2max = 400, # sample size region
               stepn2 = 4, # sample size step size
               kappamin = 0.02, kappamax = 0.2, # threshold region
               stepkappa = 0.02, # threshold step size
               c2 = 0.675, c3 = 0.72, # maximal total trial costs
               c02 = 15, c03 = 20, # maximal per-patient costs
               b1 = 3000, b2 = 8000, b3 = 10000, # gains for patients
               alpha = 0.025, # one-sided significance level
               beta = 0.1, # 1 - power
               w = 0.6, in1 = 300, in2 = 600, # weight and amount of information
               a = 0.25, b = 0.75) # truncation values
#> Optimization result:
#>  Utility: 3073.85
#>  Sample size:
#>    phase II: 84, phase III: 194, total: 278
#>  Probability to go to phase III: 0.99
#>  Total cost:
#>    phase II: 72, phase III: 160, cost constraint: Inf
#>  Fixed cost:
#>    phase II: 15, phase III: 20
#>  Variable cost per patient:
#>    phase II: 0.675, phase III: 0.72
#>  Effect size categories (expected gains):
#>   small: 0 (3000), medium: 0.5 (8000), large: 0.8 (10000)
#>  Success probability: 0.85
#>  Success probability by effect size:
#>    small: 0.69, medium: 0.15, large: 0.01
#>  Significance level: 0.025
#>  Targeted power: 0.9
#>  Decision rule threshold: 0.06 [Kappa] 
#>  Parameters of the prior distribution: 
#>    Delta1: 0.625, Delta2: 0.8, in1: 300, in2: 600,
#>    a: 0.25, b: 0.75, w: 0.6
#>  Treatment effect offset between phase II and III: 0 [gamma]

drugdevelopR functions

The drugdevelopR package provides the functions

• optimal_tte,
• optimal_binary, and
• optimal_normal

to plan optimal phase II/III drug development programs with

• time-to-event (treatment effect measured by hazard ratio, HR),
• binary (treatment effect measured by risk ratio, RR), or
• normally distributed (treatment effect measured by standardized difference in means, Delta)

endpoints, where the treatment effect is modelled on a prior distribution. Optimal phase II/III drug development planning with fixed treatment effects can be done with the help of the R Shiny application basic.

Extensions to the basic setting are:

• optimal planning of programs including methods for discounting of phase II results (function: optimal_bias, App: bias),
• optimal planning of programs with several phase III trials (function: optimal_multitrial, App: multitrial) and
• optimal planning of programs with multiple arms (function: optimal_multiarm, App: multiarm).

Sterniii3/drugdevelopR documentation built on Jan. 26, 2024, 6:17 a.m.