The use of surrogate outcomes in model-based cost-effectiveness analyses: a survey of UK Health Technology Assessment reports.

OBJECTIVES To explore the use of surrogate outcomes in Health Technology Assessment (HTA) and provide a basis for guidance for their future use, validation and reporting. This report focuses on the role of surrogate outcomes in cost-effectiveness models (CEMs) within UK HTA Programme reports. DATA SOURCES Reports published in the UK HTA Programme monograph series in 2005 and 2006 formed the sampling frame for this study. REVIEW METHODS Reports were selected on the basis that they addressed a treatment effectiveness/efficacy question, that they included a CEM and that the CEM was primarily based on a surrogate outcome. Reports addressing diagnostic, screening, aetiology, prognostic and methodological questions were excluded. Information was extracted from included reports by two reviewers using a standardised proforma. Surrogate outcomes were assessed according to two published validation frameworks [Journal of the American Medical Association (JAMA) criteria and Outcomes Measures in Rheumatology Clinical Trials (OMERACT) scoring schema]. A narrative synthesis of findings is presented in the form of tabular summaries and illustrative qualitative quotations. RESULTS A total of 35 UK HTA reports published in 2005 and 2006 addressed an effectiveness/efficacy question and contained a CEM. Of these, four were found to have based their CEM on a surrogate outcome. All four reports sourced treatment-related changes in surrogate outcomes through a systematic review of the literature; however, there was some variability in the consistency and transparency by which these reports provided evidence of the validation for the surrogate-final outcome relationship. Only one of the reports undertook a systematic review to specifically seek the evidence base for the association between surrogate and final outcomes. Furthermore, this was the only report to provide level 1 surrogate-final outcome validation evidence, i.e. RCT data showing a strong association between the change in surrogate outcome (BPAR) and the change in final outcome (graft survival) at an individual patient level. This report met the JAMA criteria for acceptable evidence of a surrogate. Two reports provided level 2 evidence, i.e. observational study data showing the relationship between the surrogate and final outcome, and one report provided level 3 evidence, i.e. a review of disease natural history. None of the four reports achieved a sufficient score on the OMERACT schema to be judged to have acceptable evidence of a surrogate outcome by its authors. CONCLUSIONS In this survey of UK HTA reports about 10% of the CEMs therein were explicitly based on surrogate outcomes. The strength of evidence for the surrogate-final outcome relationship, transparency of quantification and exploration of uncertainty of this relationship were found to vary considerably. Recommendations are made for the use of surrogate outcomes in future HTA reports.