Ciani, O., Cantrell, A. orcid.org/0000-0003-0040-9853, Davis, S. orcid.org/0000-0002-6609-4287 et al. (6 more authors) (2014) Validation of Surrogate Endpoints in Advanced Solid Tumors: Systematic Review of Statistical Methods, Results, and Implications for Policy Makers. International Journal of Technology Assessment in Health Care, 30 (3). pp. 312-324. ISSN 0266-4623
Abstract
Objectives: Licensing of, and coverage decisions on, new therapies should rely on evidence from patient-relevant endpoints such as overall survival (OS). Nevertheless, evidence from surrogate endpoints may also be useful, as it may not only expedite the regulatory approval of new therapies but also inform coverage decisions. It is, therefore, essential that candidate surrogate endpoints be properly validated. However, there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers. Methods: We review current statistical approaches to surrogate-endpoint validation based on meta-analysis in various advanced-tumor settings. We assessed the suitability of two surrogates (progression-free survival [PFS] and time-to-progression [TTP]) using three current validation frameworks: Elston and Taylor's framework, the German Institute of Quality and Efficiency in Health Care's (IQWiG) framework and the Biomarker-Surrogacy Evaluation Schema (BSES3). Results: A wide variety of statistical methods have been used to assess surrogacy. The strength of the association between the two surrogates and OS was generally low. The level of evidence (observation-level versus treatment-level) available varied considerably by cancer type, by evaluation tools and was not always consistent even within one specific cancer type. Conclusions: Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated. According to IQWiG's framework, only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents. Our study emphasizes the challenges of surrogate-endpoint validation and the importance of building consensus on the development of evaluation frameworks.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 Cambridge University Press. Article available under the terms of the CC-BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
Keywords: | surrogate outcomes; PFS; TTP; metastatic cancer; validation |
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: | 22 Apr 2016 11:00 |
Last Modified: | 04 May 2020 13:28 |
Published Version: | http://dx.doi.org/10.1017/S0266462314000300 |
Status: | Published |
Publisher: | Cambridge University Press |
Refereed: | Yes |
Identification Number: | 10.1017/S0266462314000300 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98519 |