An introduction to group sequential methods: planning and multi-aspect optimization

TL;DR

This paper introduces group sequential methods for clinical trial design, focusing on planning, optimization, and presenting key operating characteristics to improve trial efficiency and regulatory acceptance.

Contribution

It provides a comprehensive overview of group sequential methodology, including optimization techniques and how to communicate results for decision-making.

Findings

Efficient early stopping rules for success

Methods for estimating and optimizing operating characteristics

Guidance on presenting design choices to stakeholders

Abstract

A group sequential clinical trial design can be an attractive option when planning a pivotal trial as this approach has the ability to stop the trial early for success, whilst also being well accepted from a regulatory review perspective. Compared to a single stage design there are more moving parts to consider and optimise when planning a group sequential trial. This tutorial briefly outlines the group sequential methodology before detailing some of the key operating characteristics and how these can be estimated, optimised and ultimately presented to decision makers when aligning on a final study design.