title: Time to Review the Role of Surrogate End Points in Health Policy: State of the Art and the Way Forward.
abstract: The efficacy of medicines, medical devices, and other health technologies should be proved in trials that assess final patient-relevant outcomes such as survival or morbidity. Market access and coverage decisions are, however, often based on surrogate end points, biomarkers, or intermediate end points, which aim to substitute and predict patient-relevant outcomes that are unavailable because of methodological, financial, or practical constraints. We provide a summary of the present use of surrogate end points in health care policy, discussing the case for and against their adoption and reviewing validation methods. We introduce a three-step framework for policymakers to handle surrogates, which involves establishing the level of evidence, assessing the strength of the association, and quantifying relations between surrogates and final outcomes. Although the use of surrogates can be problematic, they can, when selected and validated appropriately, offer important opportunities for more efficient clinical trials and faster access to new health technologies that benefit patients and health care systems.
authors.affiliation: Evidence Synthesis and Modelling for Health Improvement, Institute of Health Research, University of Exeter Medical School, Exeter, UK; Centre for Research on Health and Social Care Management, Bocconi University, Milan, Italy. Electronic address: o.ciani@exeter.ac.uk.
authors.forename: Oriana
authors.initials: O
authors.lastname: Ciani
authors.affiliation: International Drug Development Institute, Louvain-la-Neuve, Belgium; CluePoints, Inc., Cambridge, MA, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.affiliation: Centre for Health Economics, University of York, York, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Drummond
authors.affiliation: European Medicines Agency, London, UK; University "Tor Vergata," Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Rasi
authors.affiliation: Dendrix Research, Sao Paulo, Brazil.
authors.forename: Everardo D
authors.initials: ED
authors.lastname: Saad
authors.affiliation: Evidence Synthesis and Modelling for Health Improvement, Institute of Health Research, University of Exeter Medical School, Exeter, UK.
authors.forename: Rod S
authors.initials: RS
authors.lastname: Taylor
mesh_terms: D015415:Biomarkers; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D019317:Evidence-Based Medicine; D006291:Health Policy; D006801:Humans; D008495:Medical Oncology; D019057:Quality-Adjusted Life Years; D013673:Technology Assessment, Biomedical; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015415:Biomarkers
keywords: clinical outcome assessment; health technology assessment; surrogate end points; validation