REVIEW OF SURROGATE ENDPOINT VALIDATION METHODOLOGIES AND APPLICATION IN SOLID TUMOUR HTAS
Author(s)
Hopkinson D1, Chadwick C1, Bibi M1, Bastian A2
1McCann Health, Macclesfield, UK, 2Incyte Corporation, Wilmington, DE, USA
OBJECTIVES: There are currently no universally accepted surrogate endpoints for overall survival in trials of solid tumours. We aimed to conduct a literature review of methods that have been utilised to validate surrogate endpoints, and assess how these methods have been applied in health technology assessments (HTA). METHODS: Using the key words ‘surrogate endpoint’, ‘correlation’ and ‘regression’, searches of MEDLINE, EMBASE, Cochrane Library, ISPOR, ASCO and ESMO (2012-2017) were conducted to identify studies reporting methodologies for validating surrogate endpoints. A number of national HTA agencies (NICE, SMC, HAS, PBAC, IQWIG and pCODR) were also searched to investigate the use and critique of these methods, with a focus on solid tumours. RESULTS: The foremost methodologies for surrogate validation reported in the literature include multi-trial approaches (meta-analytic analyses, informatics theoretic approach and surrogate threshold effect [STE]) and causal inference (causal association and principal stratification). Of the six HTA agencies investigated, only IQWiG and PBAC suggest preferred methodologies for the validation of surrogate endpoints, citing meta-analytic analyses and STE. A search for solid tumour HTAs examining the validity of surrogate endpoints returned eight results. Negative decisions were reported for axitinib in kidney cancer (PBAC), dabrafenib in melanoma (IQWiG), palbocliclib in breast cancer (IQWiG), and pertuzumab in breast cancer (SMC and pCODR). Positive decisions were reported for imatinib in GIST (PBAC), pertuzumab in breast cancer (NICE) and vandetanib in thyroid cancer (pCODR), despite a lack of statistical evidence for surrogate validation. Reasons for rejection of surrogate endpoints included lack of appropriate and robust methodology, inclusion of non-comparable treatments, regimens or endpoints, exclusion of relevant trials, and lack of relevant sensitivity analyses. CONCLUSIONS: There is currently no clear consensus on how to validate surrogate endpoints. The design of appropriate and robust methodologies will be required to validate surrogate endpoints for use in solid tumour HTAs.
Conference/Value in Health Info
2017-11, ISPOR Europe 2017, Glasgow, Scotland
Value in Health, Vol. 20, No. 9 (October 2017)
Code
PRM9
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Oncology