Calculating the net clinical benefit in neuro-oncology clinical trials using two methods: Quality-adjusted survival effect sizes and joint modeling

Marijke B. Coomans*, Linda Dirven, Neil K. Aaronson, Brigitta G. Baumert, Martin Van Den Bent, Andrew Bottomley, Alba A. Brandes, Olivier Chinot, Corneel Coens, Thierry Gorlia, Ulrich Herrlinger, Florence Keime-Guibert, Annika Malmström, Francesca Martinelli, Jeff A. Sloan, Roger Stupp, Andrea Talacchi, Michael Weller, Wolfgang Wick, Jaap C. ReijneveldMartin J.B. Taphoorn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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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: 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: 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: Both methods resulted in different outcomes, but adjusting for the impact of treatment on HRQoL resulted in theoretically reduced survival benefits.

Original languageEnglish
Article numbervdaa147
JournalNeuro-Oncology Advances
Issue number1
Publication statusPublished - Jan 2020

Bibliographical note

This study was funded with a grant from the European
Organisation for Research and Treatment of Cancer (EORTC)
Quality of Life Group [grant application number: CODAGLIO v1
005 2015].

Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.


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