Design methods for medical and clinical studies

Design methods for medical and clinical studies

Date: Thursday 16 December 2021, 2.00PM
Location: Online
Online - joining instructions will be sent to those registered
Section Group Meeting

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2pm – 2:40pm
Kaspar Rufibach (Roche)
Answering Old Questions with New Tools: Application of the ICH E9 Addendum in Oncology

In this talk I will discuss the application of the ICH E9(R1) estimand addendum to oncology clinical trials. Using trial examples I will illustrate how the estimand framework supports transparent formulation of clinical trial objective(s) for the following challenging drug development questions:
  • Complexity of treatment options and existence of potential curative procedures (such as e.g. CAR-T) or treatment sequence across different phases in hematological trials.
  • Treatment switching.
  • Impact of post-randomization events on efficacy.
Often, such type of questions are answered using simplified analyses that are only valid under strong assumptions. To make these assumptions transparent we will discuss estimands, estimation methods, and impact on data collection.
More on the oncology estimand WG:

Stefanie Biedermann (Open University)
D-optimal designs for multiarm trials with dropouts

(joint work with Kim May Lee and Robin Mitra)

Multiarm trials with follow-up on participants are commonly implemented to assess treatment effects on a population over the course of the studies. Dropout is an unavoidable issue especially when the duration of the multiarm study is long. Its impact is often ignored at the design stage, which may lead to less accurate statistical conclusions. We develop an optimal design framework for trials with repeated measurements, which takes potential dropouts into account, and we provide designs for linear mixed models where the presence of dropouts is noninformative and dependent on design variables. Our framework is illustrated through redesigning a clinical trial on Alzheimer's disease, whereby the benefits of our designs compared with standard designs are demonstrated through simulations.

Break: 3.20pm – 3.50pm

3.50pm – 4.30pm
Tom Burnett (Bath)
The missing data problem in adaptive clinical trials

Abstract: Adaptive designs allow pre-planned modification of trials in progress based on the accumulating data. When used appropriately this has many potential benefits such as more flexible, ethical, and efficient trials. However, these benefits rely on the ability to be able to make good decisions at the pre-planned interim analyses. Due to the rolling nature of recruitment at an interim point in the trial, there are patients who have been recruited but who do not provide data for the interim decision making. This creates a limitation for adaptive designs where the data must be relatively quickly observed in order to make good decisions in a timely manner.


We illustrate how the adaptive nature of a trial directly causes this missing data problem. Showing how this subsequently influences the efficiency of the design and giving an understanding of where this may be a problem. We shall discuss some potential solutions to this problem and how these may increase the viability of adaptive designs in practice.

Panel Discussion: 4.30pm – 5pm
Kaspar Rufibach (Roche)
Stefanie Biedermann (Open University)
Tom Burnett (Bath)
Robin Mitra for RSS Medical Section
Free for RSS Fellows
£10 for non-Fellows