Imperial College London

Professor Anthony Gordon

Faculty of MedicineDepartment of Surgery & Cancer

Chair in Anaesthesia and Critical Care
 
 
 
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Contact

 

+44 (0)20 3312 6328anthony.gordon

 
 
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Location

 

ICUQueen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wong:2018:10.1136/bmjopen-2017-020068,
author = {Wong, JLC and Mason, A and Gordon, A and Brett, S},
doi = {10.1136/bmjopen-2017-020068},
journal = {BMJ Open},
title = {Are large randomized controlled trials in severe sepsis and septic shock statistically disadvantaged by repeated inadvertent underestimates of required sample size},
url = {http://dx.doi.org/10.1136/bmjopen-2017-020068},
volume = {8},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Objectives: We sought to understand why randomized controlled trials in septic shock have failed to demonstrate effectiveness in the face of improving overall outcomes for patients and seemingly promising results of early phase trials of interventions. Design: We performed a retrospective analysis of large critical care trials of severe sepsis and septic shock. Data were collected from the primary trial manuscripts, pre-published statistical plans or by direct communication with corresponding authors. Setting: Critical care randomized control trials in severe sepsis and septic shock. Participants: 14619 patients randomized in 13 trials published between 2005 to 2015, enrolling greater than 500 patients and powered to a primary outcome of mortality. Intervention: Multiple interventions including the evaluation of treatment strategies and novel therapeutics. Primary and secondary outcome measures: Our primary outcome measure was the difference between the anticipated and actual control arm mortality. Secondary analysis examined the actual effect size and the anticipated effect size employed in sample size calculation. Results: In this post-hoc analysis of 13 trials with 14 619 patients randomised, we highlight a global tendency to overestimate control arm mortality in estimating sample size (absolute difference 9.8%, 95% confidence interval, -14.7% to -5%, p<0.001). When we compared anticipated and actual effect size of a treatment there was also a substantial overestimation in proposed values (absolute difference 7.4%, 95% confidence interval -9.0% to -5.8%, p<0.0001). Conclusions: An interpretation of our results is that trials are consistently underpowered in the planning phase by employing erroneous variables to calculate a satisfactory sample size. Our analysis cannot establish if, given a larger sample size, a trial would have had a positive result. It is disappointing so many promising phase II res
AU - Wong,JLC
AU - Mason,A
AU - Gordon,A
AU - Brett,S
DO - 10.1136/bmjopen-2017-020068
PY - 2018///
SN - 2044-6055
TI - Are large randomized controlled trials in severe sepsis and septic shock statistically disadvantaged by repeated inadvertent underestimates of required sample size
T2 - BMJ Open
UR - http://dx.doi.org/10.1136/bmjopen-2017-020068
UR - http://hdl.handle.net/10044/1/61249
VL - 8
ER -