Baseline-adjusted proportional odds models for the quantification of treatment effects in trials with ordinal sum score outcomes.
Clinical trial
Distribution regression
EMSCI
NISCI
Odds ratio
Ordinal scores
Spinal cord
Spinal cord independence measure (SCIM)
Sygen®
Transformation model
Upper extremity motor score (UEMS)
Journal
BMC medical research methodology
ISSN: 1471-2288
Titre abrégé: BMC Med Res Methodol
Pays: England
ID NLM: 100968545
Informations de publication
Date de publication:
06 05 2020
06 05 2020
Historique:
received:
20
03
2019
accepted:
20
04
2020
entrez:
8
5
2020
pubmed:
8
5
2020
medline:
25
6
2021
Statut:
epublish
Résumé
Sum scores of ordinal outcomes are common in randomized clinical trials. The approaches routinely employed for assessing treatment effects, such as t-tests or Wilcoxon tests, are not particularly powerful in detecting changes in relevant parameters or lack the ability to incorporate baseline information. Hence, tailored statistical methods are needed for the analysis of ordinal outcomes in clinical research. We propose baseline-adjusted proportional odds logistic regression models to overcome previous limitations in the analysis of ordinal outcomes in randomized clinical trials. For the validation of our method, we focus on common ordinal sum score outcomes of neurological clinical trials such as the upper extremity motor score, the spinal cord independence measure, and the self-care subscore of the latter. We compare the statistical power of our models to other conventional approaches in a large simulation study of two-arm randomized clinical trials based on data from the European Multicenter Study about Spinal Cord Injury (EMSCI, ClinicalTrials.gov Identifier: NCT01571531). We also use the new method as an alternative analysis of the historical Sygen®clinical trial. The simulation study of all postulated trial settings demonstrated that the statistical power of the novel method was greater than that of conventional methods. Baseline adjustments were more suited for the analysis of the upper extremity motor score compared to the spinal cord independence measure and its self-care subscore. The proposed baseline-adjusted proportional odds models allow the global treatment effect to be directly interpreted. This clear interpretation, the superior statistical power compared to the conventional analysis approaches, and the availability of open-source software support the application of this novel method for the analysis of ordinal outcomes of future clinical trials.
Sections du résumé
BACKGROUND
Sum scores of ordinal outcomes are common in randomized clinical trials. The approaches routinely employed for assessing treatment effects, such as t-tests or Wilcoxon tests, are not particularly powerful in detecting changes in relevant parameters or lack the ability to incorporate baseline information. Hence, tailored statistical methods are needed for the analysis of ordinal outcomes in clinical research.
METHODS
We propose baseline-adjusted proportional odds logistic regression models to overcome previous limitations in the analysis of ordinal outcomes in randomized clinical trials. For the validation of our method, we focus on common ordinal sum score outcomes of neurological clinical trials such as the upper extremity motor score, the spinal cord independence measure, and the self-care subscore of the latter. We compare the statistical power of our models to other conventional approaches in a large simulation study of two-arm randomized clinical trials based on data from the European Multicenter Study about Spinal Cord Injury (EMSCI, ClinicalTrials.gov Identifier: NCT01571531). We also use the new method as an alternative analysis of the historical Sygen®clinical trial.
RESULTS
The simulation study of all postulated trial settings demonstrated that the statistical power of the novel method was greater than that of conventional methods. Baseline adjustments were more suited for the analysis of the upper extremity motor score compared to the spinal cord independence measure and its self-care subscore.
CONCLUSIONS
The proposed baseline-adjusted proportional odds models allow the global treatment effect to be directly interpreted. This clear interpretation, the superior statistical power compared to the conventional analysis approaches, and the availability of open-source software support the application of this novel method for the analysis of ordinal outcomes of future clinical trials.
Identifiants
pubmed: 32375705
doi: 10.1186/s12874-020-00984-2
pii: 10.1186/s12874-020-00984-2
pmc: PMC7204322
doi:
Banques de données
ClinicalTrials.gov
['NCT01571531']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104Commentaires et corrections
Type : ErratumIn
Références
Spine (Phila Pa 1976). 2001 Dec 15;26(24 Suppl):S68-86
pubmed: 11805613
Brain. 2012 Apr;135(Pt 4):1224-36
pubmed: 22505632
J Pharmacokinet Pharmacodyn. 2011 Aug;38(4):497-517
pubmed: 21688068
Stat Med. 2013 Aug 15;32(18):3181-91
pubmed: 23401181
Arch Phys Med Rehabil. 2004 Nov;85(11):1804-10
pubmed: 15520975
J Neurotrauma. 2008 Jun;25(6):677-85
pubmed: 18578636
Stat Med. 1993 Dec 30;12(24):2257-71
pubmed: 8134732
Stat Med. 2017 Nov 30;36(27):4316-4335
pubmed: 28872693
Spinal Cord. 2007 Apr;45(4):275-91
pubmed: 16909143
Biostatistics. 2019 Jul 1;20(3):546-548
pubmed: 30561505
J Spinal Cord Med. 2011 Nov;34(6):547-54
pubmed: 22330109
Stat Med. 2018 Nov 30;37(27):3991-4006
pubmed: 29984411
N Engl J Med. 1990 May 17;322(20):1405-11
pubmed: 2278545
Scand J Pain. 2016 Oct;13:67-75
pubmed: 28850536
Curr Opin Neurobiol. 2014 Aug;27:53-60
pubmed: 24632308
BMJ. 2001 Nov 10;323(7321):1123-4
pubmed: 11701584
Spinal Cord. 2017 Aug;55(8):730-738
pubmed: 28322239
Neurorehabil Neural Repair. 2012 Nov-Dec;26(9):1064-71
pubmed: 22647878
Spine (Phila Pa 1976). 2001 Dec 15;26(24 Suppl):S87-98
pubmed: 11805614
Arch Phys Med Rehabil. 2011 Mar;92(3):369-75
pubmed: 21353821
BMC Med Res Methodol. 2016 Nov 8;16(1):149
pubmed: 27821067
Stat Med. 2014 Aug 15;33(18):3078-88
pubmed: 24648378
Nat Med. 2006 Jul;12(7):790-2
pubmed: 16819551
Neurorehabil Neural Repair. 2009 Jun;23(5):413-21
pubmed: 19261766
Disabil Rehabil. 2001 Apr 15;23(6):263-8
pubmed: 11336099
J Spinal Cord Med. 2011 Nov;34(6):535-46
pubmed: 22330108
Spine (Phila Pa 1976). 2001 Dec 15;26(24 Suppl):S58-67
pubmed: 11805612
Spinal Cord. 2002 Aug;40(8):396-407
pubmed: 12124666
Spinal Cord. 2011 Feb;49(2):257-65
pubmed: 20714334