Skip to main content Accessibility help

Use of surrogate outcomes in cost-effectiveness models: A review of United Kingdom health technology assessment reports1

  • Julian Elston (a1) and Rod S. Taylor (a2)


Objectives: The aim of this study was to explore the use of surrogate outcomes—a substitute outcome that predicts final patient-related outcomes—in cost-effectiveness models (CEM) within health technology assessment (HTA) reports and provide guidance for their future use.

Methods: Our sampling frame was all UK HTA Program monograph series reports published in 2005 and 2006. Reports were included if they addressed a treatment effectiveness/efficacy question and included a CEM based on a surrogate outcome. The two authors independently applied inclusion and exclusion criteria, and the following data was extracted from included reports: source of surrogate outcome, level of evidence for validation of the surrogate outcomes, methods used in report to quantify link between surrogate outcome and final outcome, and consideration of the uncertainty associated with using surrogate outcomes in the results or conclusions of report.

Results: Of 100 HTA reports, 35 complied with the inclusion criteria. Of these, four (11 percent) reports included a CEM based on a surrogate outcome. All four reports sourced treatment-related changes in surrogate outcome through a systematic review of the literature. One provided Level 1 surrogate evidence (randomized controlled trial data showing a strong association between the change in surrogate outcome and change final outcome); two reported Level 2 evidence (observational study data); and one provided Level 3 evidence (disease natural/ history data). The transparency of quantification and exploration of uncertainty of the surrogate and final outcome relationship varied considerably across all four reports.

Conclusions: Recommendations are made for the use of surrogate outcomes in future HTA reports.



Hide All
1. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred and conceptual framework. Clin Pharmacol Ther. 2001;22:485502.
2. Bucher, HC, Guyatt, GH, Cook, DJ, Holbrook, A, McAlister, FA. Users' guides to the medical literature: XIX. Applying clinical trial results. A. How to use an article measuring the effect of an intervention on surrogate end points. Evidence-Based Medicine Working Group. JAMA. 1999;282:771778.
3. Fitzpatrick, R, Davey, C, Buxton, MJ, Jones, DR. Evaluating patient-based outcome measures for use in clinical trials. Health Technol Assess. 1998;2:17.
4. Fleming, TR, DeMets, DL. Surrogate end points in clinical trials: Are we being misled? Ann Intern Med. 1996;125:605613.
5. Gotzsche, PC, Liberati, A, Torri, V, Rossetti, L. Beware of surrogate outcome measures. Int J Technol Assess Health Care. 1996;12:238246.
6. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Statistical principles for clinical trials E9. February 1998. Accessed October 17, 2008.
7. Lassere, MN, Johnson, KR, Boers, M, et al. Definitions and validation criteria for biomarkers and surrogate endpoints: Development and testing of a quantitative hierarchical levels of evidence schema. J Rheumatol. 2007;34:607615.
8. Loveman, E, Green, C, Kirby, J, et al. The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer's disease. Health Technol Assess. 2006;10:1160.
9. NICE. Guide to the methods of technology appraisal. London: National Institute for Health and Clinical Excellence; April 2008. Accessed October 17, 2008.
10. Ridker, PM, Torres, J. Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005. JAMA. 2006;295:22702274.
11. Shepherd, J, Jones, J, Takeda, A, Davidson, P, Price, A. Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic hepatitis B: A systematic review and economic evaluation. Health Technol Assess. 2006;10 (28):1183.
12. Taylor, RS, Elston, J. The use of surrogate outcomes in model-based cost-effectiveness analyses: A review of UK health technology assessment reports. Health Technol Assess. In press.
13. U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: Patient-reported outcome measures: Use in medical product development to support labeling claims: Draft guidance. Health Qual Life Outcomes 2006;4:79.
14. Woodroffe, R, Yao, GL, Meads, C, et al. Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: A systematic review and modelling study. Health Technol Assess. 2005;9:1179.
15. Yao, G, Albon, E, Adi, Y, et al. A systematic review and economic model of the clinical and cost-effectiveness of immunosuppressive therapy for renal transplantation in children. Health Technol Assess. 2006;10: iiiiv, ix–xi, 1–157.


Type Description Title
Supplementary Material

Elston supplementary table
Elston supplementary table

 Word (187 KB)
187 KB


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed