Journal Article

Using Bayesian adaptive designs to improve phase III trials: a respiratory care example

Gates, Simon, Ryan, Elizabeth G., Young, Duncan, Viele, Kert, Bruce, Julie, Metcalfe, Andrew J., Lamb, Sarah E., Stallard, Nigel

2019

Overview

Background Bayesian adaptive designs can improve the efficiency of trials, and lead to trials that can produce high quality evidence more quickly, with fewer patients and lower costs than traditional methods. The aim of this work was to determine how Bayesian adaptive designs can be constructed for phase III clinical trials in critical care, and to assess the influence that Bayesian designs would have on trial efficiency and study results. Methods We re-designed the High Frequency OSCillation in Acute Respiratory distress syndrome (OSCAR) trial using Bayesian adaptive design methods, to allow for the possibility of early stopping for success or futility. We constructed several alternative designs and studied their operating characteristics via simulation. We then performed virtual re-executions by applying the Bayesian adaptive designs using the OSCAR data to demonstrate the practical applicability of the designs. Results We constructed five alternative Bayesian adaptive designs and identified a preferred design based on the simulated operating characteristics, which had similar power to the original design but recruited fewer patients on average. The virtual re-executions showed the Bayesian sequential approach and original OSCAR trial yielded similar trial conclusions. However, using a Bayesian sequential design could have led to a reduced sample size and earlier completion of the trial. Conclusions Using the OSCAR trial as an example, this case study found that Bayesian adaptive designs can be constructed for phase III critical care trials. If the OSCAR trial had been run using one of the proposed Bayesian adaptive designs, it would have terminated at a smaller sample size with fewer deaths in the trial, whilst reaching the same conclusions. We recommend the wider use of Bayesian adaptive approaches in phase III clinical trials. Trial registration OSCAR Trial registration ISRCTN, ISRCTN10416500 . Retrospectively registered 13 June 2007.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult respiratory distress syndrome / Bayes Theorem / Bayesian analysis / Bayesian sequential design / Care and treatment / Clinical trials / Clinical Trials, Phase III as Topic - methods / Computer Simulation / Critical care / Critical Care - methods / Design / Health Sciences / Humans / Hypothesis testing / Interim analyses / Medicine / Medicine & Public Health / Methods / Mortality / Randomised controlled trials / Randomized Controlled Trials as Topic - methods / Research Article / Research Design / Respiratory distress syndrome / Respiratory Distress Syndrome - mortality / Respiratory Distress Syndrome - therapy / Respiratory therapy / Sample Size / Statistical Theory and Methods / Statistics for Life Sciences / Study design / Success / Testing / Theory of Medicine/Bioethics / Ventilators