Assessing the use and validation of surrogate outcomes in health technology assessment

Surrogate outcomes have been defined as biomarkers or laboratory measures used as substitutes for final patient-relevant outcomes in clinical trials in order to assess the efficacy of health technologies. The advantages of surrogate over final outcomes are that they may occur faster or may be easier to assess, thereby shortening the duration, size, and cost of clinical trials. But relying on surrogate outcomes evidence alone has been shown to lead to unreliable conclusions about the value of new treatments.
As part of a PhD and postdoctoral research work, we have explored key issues related to the use of surrogate outcomes in HTA and contributed to improve technology appraisal that uses surrogate outcomes evidence. Oriana Ciani and Rod Taylor have been involved in the update of the Methods Guidance for Technology Appraisal at the National Institute of Health and Care Excellence (NICE) released in 2013 (http://publications.nice.org.uk/guide-to-the-methods-of-technology-appraisal-2013-pmg9), as well as to the EUnetHTA guideline for surrogate endpoints in Relative Effectiveness Assessment (REA) of pharmaceuticals (http://www.eunethta.eu/sites/5026.fedimbo.belgium.be/files/Surrogate%20Endpoints.pdf). They are also collaborating with colleagues at the University of Leicester on the joint use of multiple surrogate endpoints to improve their predictive value.
Future research development will involve application of trial-level and individual patients data validation strategies to putative surrogate outcomes in cardiovascular diseases.

Publications:
Ciani O, Buyse M, Drummond M, Rasi G, Saad ED, Taylor RS. Time to review the role of surrogate endpoints in health policy: state of the art and the way forward. Value in Health 2016 (in press)

Ciani O, Buyse M, Drummond M, Rasi G, Saad ED, Taylor RS. Use of surrogate endpoints in healthcare policy: proposal for consistent adoption of a validation framework. Nature Rev Drug Disc 2016 Jun 3. doi: 10.1038/nrd.2016.81.

Ciani O, Taylor RS. Validation of surrogate end points for overall survival in advanced colorectal cancer: A harmonized approach is needed. J Clin Epidemiol. 2016 Feb;70:277-8.

Ciani O, Buyse M, Garside R, Peter J, Saad E, Stein K, Taylor RS. Validation of surrogateoutcomes for overall survival in advanced colorectal cancer: a systematic review and metaanalysis of randomised controlled trials. J Clin Epidemiol. 2015 Jul;68(7):833-842.

Taylor RS, Piepoli MF, Smart N, Coats AJ, Ellis S, Dalal H, O'Connor CM, Warren FC, Whellan D, Ciani O. Exercise training for chronic heart failure (ExTraMATCH II): Protocol for an individual participant data meta-analysis. Int J Cardiol. 2014 Apr 26. pii: S0167-5273(14)00885-7.

Ciani O, Davis S, Tappenden P, Garside R, Stein K, Buyse M, Saad E, Taylor RS. Validation of surrogate end points in advanced solid tumours: systematic review of statistical methods, results and implication for policy-makers. Int J Tech Assessment Health Care 2014 Jul;30(3):312-24.

Ciani O, Hoyle M, Pavey T, Cooper C, Garside R, Rudin C, Taylor RS. Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: a case-study for technology appraisal on the basis of surrogate outcomes evidence. Value in Health. 2013 Sep-Oct;16(6):1081-90. doi: 10.1016/j.jval.2013.07.004.

Ciani O, Buyse M, Garside R, Pavey T, Stein K, Sterne JA, Taylor RS. Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study. BMJ. 2013 Jan 29;346:f457. doi: 10.1136/bmj.f457.

Ciani O, Taylor RS. Surrogate, friend or foe? The need for case studies of the use of surrogate outcomes in cost-effectiveness analyses. Health Economics. 2013 Feb;22(2):251-2. doi: 10.1002/hec.2826. Epub 2012 May 24.

Taylor RS, Elston J. The use of surrogate outcomes in model-based cost-effectiveness analyses: a survey of UK health technology assessment reports. Health Technology Assessment 2009;13:8

People involved: Oriana Ciani, Sarah Walker, Rod Taylor