Clinical trial simulation
Objective and introduction
Objectives
- To appreciate the steps involved in simulating a clinical trial.
- To become familiar with the main features of the Pharsight Trial Simulator.
Introduction
The recognition that traditional methods of drug development often lead to many clinical trials that contribute little to regulatory approval (Peck 1997) has aroused interest in exploring other methods. Clinical trial simulation has been advocated as a way of getting better insight into the real questions that need to be answered by a clinical trial. The process of model building in itself is a powerful method of understanding what is known and what remains to be discovered. Simulation of a clinical trial can provide a data set that will resemble the results of an actual trial. This can be used for preparing clinical trial databases and rehearsing analysis plans. Multiple replications of a clinical trial simulation can be used as a form of meta-analysis to refine clinical trial designs.
The principles of clinical trial simulation are described in:
- Holford NHG, Kimko HC, Monteleone JPR, Peck CC. Simulation of clinical trials. Annu. Rev. Pharmacol. Toxicol. 2000;40:209-234
- Holford N, Ma SC, Ploeger BA. Clinical trial simulation: a review. Clin Pharmacol Ther. 2010;88(2):166-82
- Smith MK, Marshall A. Importance of protocols for simulation studies in clinical drug development. Stat Methods Med Res. 2010
Pharsight Trial Simulator
- Pharsight Trial Simulator
The Trial Simulator is a tool for creating models and defining clinical trial designs. It allows the simulation of the trials and offers the ability to analyse the results and explore the effectiveness of the design. - Quick Tour
- Start Pharsight Trial Simulator using the shortcut in the Pharmacometrics Programs folder.
- Follow the instructions for the Quick Tour (look in the Help menu for Trial Simulator).
- Try to complete the Quick Tour example (this will take about 2 hours to complete).
- Save the QuickTour.std file in My Pharmacometrics\Pharmacometrics Data\Clinical Trial Design and Simulation
- Note: There is a mistake in the instructions for the Quick Tour (Delta_Factor_Y Response block). You cannot enter Display Units in the Block Properties dialog for a Response:
- Note: When running the first simulation be sure to save as "QuickTourNoVar.mdb" when prompted for a file name.
- Note: In step 4 of looking at Results you will find the Results View Page menu item at the very top of the TS2 window.
Assignment
- Describe what information you would need to design a clinical trial that would be used to test the target concentration strategy for theophylline i.e. is there a clinically significant difference in peak flow and adverse effects when a target concentration of 10 or 20 mg/L is chosen to guide dosage.
- Try using Pharsight Trial Simulator to simulate this clinical trial. Attach the Trial Simulator .std file to show your clinical trial simulation design.
- Write a brief evaluation of your experiences using Pharsight Trial Simulator for:
- The Quick Tour Example.
- The Theophylline Target Concentration Strategy Trial.