Comparing randomized trial designs to estimate treatment effect in rare diseases with longitudinal models: a simulation study showcased by Autosomal Recessive Cerebellar Ataxias using the SARA score - code

This repository contains the scripts for the paper submitted to the BMC Medical Research Methodology Journal : Comparing randomized trial designs to estimate treatment effect in rare diseases with longitudinal models: a simulation study showcased by Autosomal Recessive Cerebellar Ataxias using the SARA score Authors : Hendrickx N, Mentré F, Hamdan A, Karlsson M O, Hooker A C, Traschütz A, Gagnon C, Schüle R, ARCA Study Group, EVIDENCE-RND consortium, Synofzik M, Comets E. This repository contains the NONMEM code to reproduce the simulation study of the manuscript for the slow progression case. It contains three folders, one for each design : parallel, crossover and delayed start. Each folder contains one .csv file describing the design of the simulation, 8 NONMEM model files and 2 .sh files for the simulation. There are three models : Logistic, Linear and Linear Sparse models, twice each (*_full.mod = drug effect estimated, *_red.mod = drug effect fixed to 0). The Logistic model is also present twice : *H0_* = with a simulated drug effect of 0; *H1_* = with a simulated drug effect of 0.5. There are two .sh files : *_H0.sh = simulated drug effect of 0, for type 1 error ; *_H1.sh = simulated drug effect of 0.5, for power. To get the type 1 error and power calculation, you will need to unzip the "m1.zip" folders present in "ARSACS_type1" and "ARSACS_power" to "m1_*(t1/power)*" in each design directory and run the "script_type1_power.R" script in the parent directory to get the type 1 error and corrected power for all designs, as well as the code to get the figures 4 and 5 from the manuscript. Please note that the computation time is long, especially if the commands are run locally. The commands in the .sh files are setup with 8 threads, and, depending on your CPU, the simulation study could take from 2 to 5 days per design and per simulation (Under H0 and H1) (with 500 replicates). Also, if you were to rerun the simulation, you should remove the "ARSACS_type_1" and "ARSACS_power" folders, or rename the target folder in the sse command and R script. Softwares: NONMEM 7.5.0PsN 5.3.1R 4.1.2