The Library
Bayesian group sequential designs for phase III emergency medicine trials : a case study using the PARAMEDIC2 trial
Tools
Tools
Tools
Ryan, Elizabeth G., Stallard, Nigel, Lall, Ranjit, Ji, Chen, Perkins, Gavin D. and Gates, Simon (2020) Bayesian group sequential designs for phase III emergency medicine trials : a case study using the PARAMEDIC2 trial. Trials, 21 (1). 84. doi:10.1186/s13063-019-4024-x ISSN 1745-6215.
|
PDF
WRAP-bayesian-group-sequential-designs-phase-III-emergency-medicine-trials-Stallard-2020.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1100Kb) | Preview |
Official URL: http://dx.doi.org/10.1186/s13063-019-4024-x
Abstract
Background:
Phase III trials often require large sample sizes, leading to high costs and delays in clinical decision-making. Group sequential designs can improve trial efficiency by allowing for early stopping for efficacy and/or futility and thus may decrease the sample size, trial duration and associated costs. Bayesian approaches may offer additional benefits by incorporating previous information into the analyses and using decision criteria that are more practically relevant than those used in frequentist approaches. Frequentist group sequential designs have often been used for phase III studies, but the use of Bayesian group sequential designs is less common. The aim of this work was to explore how Bayesian group sequential designs could be constructed for phase III trials conducted in emergency medicine.
Methods:
The PARAMEDIC2 trial was a phase III randomised controlled trial that compared the use of adrenaline to placebo in out-of-hospital cardiac arrest patients on 30-day survival rates. It used a frequentist group sequential design to allow early stopping for efficacy or harm. We constructed several alternative Bayesian group sequential designs and studied their operating characteristics via simulation. We then virtually re-executed the trial by applying the Bayesian designs to the PARAMEDIC2 data to demonstrate what might have happened if these designs had been used in practice.
Results:
We produced three alternative Bayesian group sequential designs, each of which had greater than 90% power to detect the target treatment effect. A Bayesian design which performed interim analyses every 500 patients recruited produced the lowest average sample size. Using the alternative designs, the PARAMEDIC2 trial could have declared adrenaline superior for 30-day survival with approximately 1500 fewer patients.
Conclusions:
Using the PARAMEDIC2 trial as a case study, we demonstrated how Bayesian group sequential designs can be constructed for phase III emergency medicine trials. The Bayesian framework enabled us to obtain efficient designs using decision criteria based on the probability of benefit or harm. It also enabled us to incorporate information from previous studies on the treatment effect via the prior distributions. We recommend the wider use of Bayesian approaches in phase III clinical trials.
Trial registration:
PARAMEDIC2 Trial registration ISRCTN, ISRCTN73485024. Registered 13 March 2014, http://www.isrctn.com/ISRCTN73485024
| Item Type: | Journal Article | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QA Mathematics | |||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Statistics and Epidemiology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
|||||||||
| Library of Congress Subject Headings (LCSH): | Clinical trials -- Statistical methods, Emergency medicine -- Research | |||||||||
| Journal or Publication Title: | Trials | |||||||||
| Publisher: | Biomed Central | |||||||||
| ISSN: | 1745-6215 | |||||||||
| Official Date: | 14 January 2020 | |||||||||
| Dates: |
|
|||||||||
| Volume: | 21 | |||||||||
| Number: | 1 | |||||||||
| Article Number: | 84 | |||||||||
| DOI: | 10.1186/s13063-019-4024-x | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 28 January 2020 | |||||||||
| Date of first compliant Open Access: | 6 February 2020 | |||||||||
| RIOXX Funder/Project Grant: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
