Watch Module 3 of Adaptive Clinical Trial Designs series

Adaptive clinical trial designs is a broad area of research which encompasses many different designs and implementation techniques. Co-organised by Ecraid and the European Respiratory Society (ERS), this six-part training series introduces the distinct types of adaptive designs and explain their advantages and limitations. Participation is free of charge (with a free ERS account) and doesn't require registration. Sign up for the series' newsletter to be notified as soon as a new module is released.

The third module in the series begins with a comprehensive introduction to group sequential designs (GSDs) and sample size re-estimation (SSR) presented by Prof. Chris Jennison. The theory is brought to life through two real-world examples – the trials REGARD-VAP and CIGMA – presented by Dr Mo Yin and Prof. Antoni Torres, respectively.

Introduction to GSDs and SSR

This introduction begins with a look at group sequential designs, including the underpinning theory and computations. We explain the potential for early stopping and show how error spending designs can cope with unpredictable group sizes at planned analysis times. We go on to contrast trials designed as group sequential tests with trials that employ sample size re-estimation. We also warn against using ad hoc rules for modifying sample size but note the similarity of efficient versions of the two types of design.

Presented by Chris Jennison, professor of statistics at University of Bath (UK).

GSD case study example: REGARD-VAP

Using the REGARD-VAP (Individualised, short-course antibiotic treatment versus usual long-course treatment for ventilator-associated pneumonia) clinical trial as an example, we discuss group sequential design for sample size calculation. Results and learning lessons from each interim analysis will be explained. Sequential group design ensures that the trial remains efficient and statistically rigorous in evaluating the clinical effect of a shortened antibiotic treatment for ventilator-associated pneumonia.

Presented by Mo Yin, infectious diseases physician at National University Hospital (Singapore).

SSR case study example: CIGMA

The administration of IV Immunoglobulins is not recommended in sepsis by the current Guidelines due to the lack of clear evidence. The Cigma trial used an adaptive group sequential design, including sample size re-estimation, to investigate the administration of enriched IgM Immunoglobulins in severe CAP. This trial did not result in a significant increase in the number of mechanical ventilator free days in the treatment group. In the post-hoc analysis of patients with higher inflammation and lower levels of Immunoglobulins a beneficial effect in the main and secondary outcomes was observed in the treatment group. According to these results a new RCT is ongoing.

Presented by Antoni Torres, professor of medicine (pulmonology) at the Hospital Clinic at University of Barcelona (Spain).

Module 4 will be released on 31 July 2024. Sign up for the series' newsletter to be notified as soon as it is out.