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Chapter 5 - Clinical Trial Simulations

from Part II - Basic Ingredients for Adaptive Trial Designs and Common Types

Published online by Cambridge University Press:  20 March 2023

Jay J. H. Park ,
Edward J. Mills  and
J. Kyle Wathen
By
Jay J. H. Park ,
Edward Mills  and
J. Kyle Wathen
Jay J. H. Park
Affiliation:
McMaster University, Ontario
Edward J. Mills
Affiliation:
McMaster University, Ontario
J. Kyle Wathen
Affiliation:
Cytel, Cambridge, Massachusetts
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Summary

In this chapter, we discuss the use of simulations for clinical trials. Simulation in statistics generally refers to repeated analyses of randomly generated datasets with known properties. Clinical trial simulation is required to explore, compare, and characterise operating characteristics and statistical properties of adaptive and other innovative trials with complex designs. Clinical trial simulation is an important tool that allows for comparison of different design choices during the planning stage to enhance the quality and feasibility of the trial. While simulations are most frequently used in adaptive and other complex trial designs, they can be applied to fixed trial designs.

Keywords

simulationsimulation-guided designmonte carlo simulationstatistical software
Type
Chapter
Information
Introduction to Adaptive Trial Designs and Master Protocols , pp. 47 - 62
Publisher: Cambridge University Press
Print publication year: 2023

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References

Gasparini, A, Morris, TP, Crowther, MJ. INTEREST: INteractive Tool for Exploring REsults from Simulation sTudies. J Data Sci Stat Vis. 2021;1(4).Google Scholar
Burton, A, Altman, DG, Royston, P, Holder, RL. The design of simulation studies in medical statistics. Stat Med. 2006;25(24):4279–92.CrossRefGoogle ScholarPubMed
Boulesteix, AL, Groenwold, RH, Abrahamowicz, M, et al. Introduction to statistical simulations in health research. BMJ Open. 2020;10(12):e039921.CrossRefGoogle ScholarPubMed
Mayer, C, Perevozskaya, I, Leonov, S, et al. Simulation practices for adaptive trial designs in drug and device development. Stat Biopharm Res. 2019;11(4):325–35.Google Scholar
United States Department of Health and Human Services, Food and Drug Administration. Adaptive Designs for Clinical Trials of Drugs and Biologics. Guidance for Industry. Center for Biologics Evaluation and Research (CBER); 2019.Google Scholar
U.S. Food and Drug Administration. Adaptive Designs for Medical Device Clinical Studies Guidance for Industry and Food and Drug Administration Staff. United States Department of Health and Human Services; 2016.Google Scholar
Hummel, J, Wang, S, Kirkpatrick, J. Using simulation to optimize adaptive trial designs: applications in learning and confirmatory phase trials. Clin Investig. 2015;5(4):401–13.Google Scholar
Gaydos, B, Anderson, KM, Berry, D, et al. Good practices for adaptive clinical trials in pharmaceutical product development. Drug Inf J. 2009;43(5):539–56.Google Scholar
Thorlund, K, Golchi, S, Haggstrom, J, Mills, E. Highly Efficient Clinical Trials Simulator (HECT): software application for planning and simulating platform adaptive trials. Gates Open Res. 2019;3:780.CrossRefGoogle ScholarPubMed
Thorlund, K, Haggstrom, J, Park, JJ, Mills, EJ. Key design considerations for adaptive clinical trials: a primer for clinicians. BMJ. 2018;360:k698.Google Scholar
Wason, JM, Brocklehurst, P, Yap, C. When to keep it simple–adaptive designs are not always useful. BMC Med. 2019;17(1):1–7.CrossRefGoogle Scholar
Thall, P, Fox, P, Wathen, J. Statistical controversies in clinical research: scientific and ethical problems with adaptive randomization in comparative clinical trials. Ann Oncol. 2015;26(8):1621–8.Google Scholar
Meyer, EL, Mesenbrink, P, Mielke, T, et al. Systematic review of available software for multi-arm multi-stage and platform clinical trial design. Trials. 2021;22(1):183.CrossRefGoogle ScholarPubMed
Weston, SJ, Yee, D. Why you should become a useR: a brief introduction to R. APS Obs. 2017;30(3).Google Scholar
Grayling, MJ, Wason, JM. A web application for the design of multi-arm clinical trials. BMC Cancer. 2020;20(1):80.Google Scholar
Wassmer, G, Pahlke, F. Rpact: confirmatory adaptive clinical trial design and analysis. R package version; 2021.Google Scholar
Kunzmann, K, Pilz, M, Herrmann, C, Rauch, G, Kieser, M. The adoptr package: adaptive optimal designs for clinical trials in R. J Stat Softw. 2021;98:1–21.Google Scholar
Granholm, A, Jensen, AKG, Lange, T, Kaas-Hansen, BS. adaptr: an R package for simulating and comparing adaptive clinical trials. J Open Source Softw. 2022;7(72):4284.Google Scholar

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