Diaz, J., Sternberg, C.N., Mehmud, F. et al. (4 more authors) (2016) Overall Survival Endpoint in Oncology Clinical Trials: Addressing the Effect of Crossover - The Case of Pazopanib in Advanced Renal Cell Carcinoma. Oncology, 90 (3). pp. 119-126. ISSN 0030-2414
Abstract
Objective: To identify the issues of using overall survival (OS) as a primary endpoint in the presence of crossover and the statistical analyses available to adjust for confounded OS due to crossover in oncology clinical trials. Methods: An indirect comparison was conducted between pazopanib and sunitinib in advanced renal cell carcinoma. Statistical adjustment methods were used to estimate the true comparative effectiveness of these treatments. Recently, a head-to-head trial comparing pazopanib and sunitinib was completed. This provided the opportunity to compare the OS treatment effect estimated for pazopanib versus sunitinib using indirect comparison and statistical adjustment techniques with that observed in the head-to-head trial. Results: Using a rank-preserving structural failure time model to adjust for crossover in the pazopanib registration trial, the indirect comparison of pazopanib versus sunitinib resulted in an OS hazard ratio (HR) of 0.97, while an unadjusted analysis resulted in an OS HR of 1.96. The head-to-head trial reported a final OS HR of 0.92 for pazopanib versus sunitinib. Conclusion: This case study supports the need to adjust for confounded OS due to crossover, which enables trials to meet ethical standards and provides decision makers with a more accurate estimate of treatment benefit.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Karger Publishers. This is an author produced version of a paper subsequently published in Oncology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Crossover; Overall survival; Pazopanib; Renal cell; Carcinoma |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Feb 2017 10:51 |
Last Modified: | 03 Nov 2017 02:54 |
Published Version: | https://doi.org/10.1159/000443647 |
Status: | Published |
Publisher: | Karger Publishers |
Refereed: | Yes |
Identification Number: | 10.1159/000443647 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:111326 |