Statistical analysis plan for the POLAR-RCT

The Prophylactic hypOthermia trial to Lessen trAumatic bRain injury-Randomised Controlled Trial

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. Methods: The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18-60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80% power to detect a 30% relative risk increase from 50% to 65% (equivalent to a 15% absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. Discussion: Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data.

Original languageEnglish
Article number259
Number of pages10
JournalTrials
Volume19
Issue number1
DOIs
Publication statusPublished - 27 Apr 2018

Keywords

  • Cooling
  • Critical care
  • Hypothermia
  • Outcome
  • Randomised controlled trials
  • Traumatic brain injury

Cite this

@article{21697e1a84f84e4dbcebcce6be5c2906,
title = "Statistical analysis plan for the POLAR-RCT: The Prophylactic hypOthermia trial to Lessen trAumatic bRain injury-Randomised Controlled Trial",
abstract = "Background: The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. Methods: The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18-60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80{\%} power to detect a 30{\%} relative risk increase from 50{\%} to 65{\%} (equivalent to a 15{\%} absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. Discussion: Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data.",
keywords = "Cooling, Critical care, Hypothermia, Outcome, Randomised controlled trials, Traumatic brain injury",
author = "Jeffrey Presneill and Dashiell Gantner and Alistair Nichol and Colin McArthur and Andrew Forbes and Jessica Kasza and Tony Trapani and Lynnette Murray and Stephen Bernard and Peter Cameron and Gilles Capellier and Olivier Huet and Lynette Newby and Stephen Rashford and Rosenfeld, {Jeffrey V.} and Tony Smith and Michael Stephenson and Dinesh Varma and Shirley Vallance and Tony Walker and Steve Webb and {James Cooper}, D.",
year = "2018",
month = "4",
day = "27",
doi = "10.1186/s13063-018-2610-y",
language = "English",
volume = "19",
journal = "Trials",
issn = "1745-6215",
publisher = "Springer-Verlag London Ltd.",
number = "1",

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TY - JOUR

T1 - Statistical analysis plan for the POLAR-RCT

T2 - The Prophylactic hypOthermia trial to Lessen trAumatic bRain injury-Randomised Controlled Trial

AU - Presneill, Jeffrey

AU - Gantner, Dashiell

AU - Nichol, Alistair

AU - McArthur, Colin

AU - Forbes, Andrew

AU - Kasza, Jessica

AU - Trapani, Tony

AU - Murray, Lynnette

AU - Bernard, Stephen

AU - Cameron, Peter

AU - Capellier, Gilles

AU - Huet, Olivier

AU - Newby, Lynette

AU - Rashford, Stephen

AU - Rosenfeld, Jeffrey V.

AU - Smith, Tony

AU - Stephenson, Michael

AU - Varma, Dinesh

AU - Vallance, Shirley

AU - Walker, Tony

AU - Webb, Steve

AU - James Cooper, D.

PY - 2018/4/27

Y1 - 2018/4/27

N2 - Background: The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. Methods: The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18-60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80% power to detect a 30% relative risk increase from 50% to 65% (equivalent to a 15% absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. Discussion: Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data.

AB - Background: The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. Methods: The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18-60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80% power to detect a 30% relative risk increase from 50% to 65% (equivalent to a 15% absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. Discussion: Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data.

KW - Cooling

KW - Critical care

KW - Hypothermia

KW - Outcome

KW - Randomised controlled trials

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=85046128909&partnerID=8YFLogxK

U2 - 10.1186/s13063-018-2610-y

DO - 10.1186/s13063-018-2610-y

M3 - Article

VL - 19

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 259

ER -