Early Phase Clinical Trials

Introduction

I lead the Early Phase Clinical Trials module at the University of Birmingham. The module is a core part of the university’s new MSc in Clinical Trials. It runs over five consecutive days from 9th to 13th March 2020.

Day One

Day one is concerned with dose-finding trials. We learn about the fundamentals of dose-finding and the perennial yet underwhelming 3+3 method. We will perform hands-on analysis using R, RStudio and Shiny web apps to simulate virtual trials and observe how the 3+3 method comes unstuck. We also delve into some of the historic disasters that have occurred in dose-finding trials and look at features in the design and conduct that can ameliorate the dangers.

Day Two

Day two builds on the material from day one by introducing model-based dose-finding methods. We focus in particular on the continual reassessment method (CRM). We learn about model fitting and interpretation, and see the method in action in practical sessions. We then look at how model-based dose-finding trials are reported in journals. We finish the day by hearing testimony from a patient on a dose-finding trial at CRCTU.

Day Three

On day three we leave dose-finding behind and turn our focus to phase II trials. On this day we learn about the different approaches to phase II trials, including the suite of optimal designs with fixed sample size, like A’Hern’s, Simon’s two-stage, and Bryant & Day’s designs. We conclude with an interview of a patient from the Clarity trial at CRCTU.

Day Four

On day four, we cover advanced topics at phase II. This includes the use of surrogate outcomes when it is impossible to observe the clinical outcome of primary interest in a reasonable time frame. We also look at co-primary outcomes, and the roles of biomarkers and subgroups.

Day Five

Day five is a special day devoted to Complex and Innovative Designs, a group that includes basket trials, umbrella trials, and platform trials. These designs have proliferated in cancer in recent years as we have discovered many potential driver mutations, allowing trialists to investigate therapies that target specific genetic aberrations. We study examples run by the University of Birmingham’s two trials units. We then look at these designs from the point of view of a competent authority, like the MHRA, the EMA or the FDA.

To learn more, visit the course webpage at https://www.birmingham.ac.uk/postgraduate/courses/taught/med/pg-modules/early-phase-clinical-trials.aspx.