Calculating the net clinical benefit in neuro-oncology clinical trials using two methods: quality-adjusted survival effect sizes and joint modeling.
glioma
joint model
net clinical benefit
quality of life
survival
Journal
Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003
Informations de publication
Date de publication:
Historique:
entrez:
7
1
2021
pubmed:
8
1
2021
medline:
8
1
2021
Statut:
epublish
Résumé
Two methods combining survival and health-related quality of life (HRQoL) data in glioma trials to calculate the "net clinical benefit" were evaluated: Quality-adjusted effect sizes (QASES) and joint modeling (JM). The net clinical benefit in two trials was calculated as proof of concept for other trials. With the QASES method, effect sizes for differences in progression-free survival (PFS) or overall survival (OS) and HRQoL between the experimental arm and standard treatment arm were calculated, while the relative emphasis placed on survival/HRQoL varied. JM allows simultaneous modeling of HRQoL and OS/PFS. In the EORTC 26951 trial, combined radiochemotherapy significantly prolonged OS (difference 11.7 months), but also resulted in more patients experiencing clinically relevant worsening (≥10 points) in appetite loss and nausea/vomiting shortly after treatment. Using QASES, the survival benefit of additional procarbazine, lomustine, and vincristine (PCV) decreased from 42.3 months to 29.5 and 28.2 months when accounting for appetite loss and nausea/vomiting, respectively. JM analyses resulted in a loss of the beneficial effect of additional PCV between 13% and 24% when adjusting for different HRQoL parameters. The EORTC 22033 trial showed no significant PFS difference between radiotherapy or temozolomide alone (46 vs 39 months), nor clinically relevant differences in HRQoL. JM analyses also showed no significant association between PFS and HRQoL scales/items, whereas QASES showed that temozolomide alone was more favorable when considering symptom burden (47-49 instead of 39 months). Both methods resulted in different outcomes, but adjusting for the impact of treatment on HRQoL resulted in theoretically reduced survival benefits.
Sections du résumé
BACKGROUND
BACKGROUND
Two methods combining survival and health-related quality of life (HRQoL) data in glioma trials to calculate the "net clinical benefit" were evaluated: Quality-adjusted effect sizes (QASES) and joint modeling (JM).
METHODS
METHODS
The net clinical benefit in two trials was calculated as proof of concept for other trials. With the QASES method, effect sizes for differences in progression-free survival (PFS) or overall survival (OS) and HRQoL between the experimental arm and standard treatment arm were calculated, while the relative emphasis placed on survival/HRQoL varied. JM allows simultaneous modeling of HRQoL and OS/PFS.
RESULTS
RESULTS
In the EORTC 26951 trial, combined radiochemotherapy significantly prolonged OS (difference 11.7 months), but also resulted in more patients experiencing clinically relevant worsening (≥10 points) in appetite loss and nausea/vomiting shortly after treatment. Using QASES, the survival benefit of additional procarbazine, lomustine, and vincristine (PCV) decreased from 42.3 months to 29.5 and 28.2 months when accounting for appetite loss and nausea/vomiting, respectively. JM analyses resulted in a loss of the beneficial effect of additional PCV between 13% and 24% when adjusting for different HRQoL parameters. The EORTC 22033 trial showed no significant PFS difference between radiotherapy or temozolomide alone (46 vs 39 months), nor clinically relevant differences in HRQoL. JM analyses also showed no significant association between PFS and HRQoL scales/items, whereas QASES showed that temozolomide alone was more favorable when considering symptom burden (47-49 instead of 39 months).
CONCLUSIONS
CONCLUSIONS
Both methods resulted in different outcomes, but adjusting for the impact of treatment on HRQoL resulted in theoretically reduced survival benefits.
Identifiants
pubmed: 33409496
doi: 10.1093/noajnl/vdaa147
pii: vdaa147
pmc: PMC7772555
doi:
Types de publication
Journal Article
Langues
eng
Pagination
vdaa147Informations de copyright
© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
Références
J Clin Oncol. 1998 Jan;16(1):139-44
pubmed: 9440735
J Clin Oncol. 2007 Dec 20;25(36):5723-30
pubmed: 18089866
Stat Med. 2011 May 30;30(12):1366-80
pubmed: 21337596
Semin Oncol. 2014 Aug;41(4):541-552
pubmed: 25173146
Biometrics. 2011 Sep;67(3):819-29
pubmed: 21306352
Chin J Cancer. 2014 Jan;33(1):40-5
pubmed: 24384239
J Clin Oncol. 2010 Jun 1;28(16):2796-801
pubmed: 20439643
Qual Life Res. 2015 Apr;24(4):795-804
pubmed: 25311306
Lancet Oncol. 2016 Nov;17(11):1521-1532
pubmed: 27686946
Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):662-9
pubmed: 19783377
J Natl Cancer Inst. 1993 Mar 3;85(5):365-76
pubmed: 8433390
Eur J Cancer. 2010 Apr;46(6):1033-40
pubmed: 20181476
J Clin Oncol. 2013 Jan 20;31(3):344-50
pubmed: 23071237