Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-23T22:24:41.186Z Has data issue: false hasContentIssue false
  • English
  • Français

ENDPOINTS FOR RELATIVE EFFECTIVENESS ASSESSMENT (REA) OF PHARMACEUTICALS

Published online by Cambridge University Press:  06 March 2015

Mira Pavlovic ,
Conor Teljeur ,
Beate Wieseler ,
Marianne Klemp ,
Irina Cleemput  and
Mattias Neyt
Mira Pavlovic
Affiliation:
La Haute Autorité de Santé [email protected]
Conor Teljeur
Affiliation:
Health Information and Quality Authority
Beate Wieseler
Affiliation:
Institute for Quality and Efficiency in Health Care
Marianne Klemp
Affiliation:
Norwegian Knowledge Centre for the Health Services
Irina Cleemput
Affiliation:
Belgian Health Care Knowledge Centre; Hasselt University
Mattias Neyt
Affiliation:
Belgian Health Care Knowledge Centre
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives: Clinical endpoints are defined as valid measures of clinical benefit or harm due to treatment, that describe the impact of treatment on how a patient feels, functions, and survives. The choice of endpoints and the manner in which they are reported have a major impact on the relative effectiveness assessment (REA) of pharmaceuticals. The aim of this article is to describe the guideline development process and the key findings that set a framework for appropriate use of endpoints in REAs in Europe.

Methods: A multi-health technology assessment (HTA)-agency collaborative process in EUnetHTA JA1 was used to scope, draft, and finalize methodological guidelines for REA in Europe.

Results: Patient-relevant clinical endpoints can be broadly categorized into: mortality, morbidity and health-related quality of life. A clinical endpoint is a main symptom or sign of a disease that is clinically relevant, valid, reproducible and responsive to change. Preference is for long-term or final endpoints whenever possible. Surrogate endpoints may be used when there is compelling evidence of a clear and consistent correlation of treatment effects on the surrogate and final outcome of interest.

Conclusions: The relevance and hierarchy of the different types of clinical endpoints depend on the research question, disease, and the treatment investigated. Not only the primary endpoint, but also other relevant endpoints are assessed in comparison to adequate comparator(s). This simultaneous assessment of all relevant endpoints is a hallmark of REA.

Keywords

Relative effectiveness assessmentClinical endpointsPatient-relevant endpoints
Type
Theme Submissions
Information
International Journal of Technology Assessment in Health Care , Volume 30 , Issue 5 , November 2014 , pp. 508 - 513
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. European Commission. Core principles on relative effectiveness. http://ec.europa.eu/enterprise/sectors/healthcare/files/docs/rea_principles_en.pdf (accessed February 11, 2015).Google Scholar
2. EUnetHTA 2013. Comparators and comparisons. Criteria for the choice of the most appropriate comparator(s). Summary of current policies and best practice recommendations. http://www.eunethta.eu/outputs/methodological-guideline-rea-pharmaceuticals-criteria-choice-most-appropriate-comparators (accessed February 11, 2015).Google Scholar
3. Berkman, N, Lohr, K, Ansari, M, et al. Grading the strength of a body of evidence when assessing health care interventions for the effective health care program of the agency for healthcare research and quality: An update. Published November 18, 2013. http://www.effectivehealthcare.ahrq.gov/ehc/products/457/1752/methods-guidance-grading-evidence-131118.pdf (accessed February 11, 2015).Google Scholar
4. Kleijnen, S, George, E, Goulden, S, et al. Relative Effectiveness Assessment of Pharmaceuticals: Similarities and Differences in 29 Jurisdictions. Value Health. 2012;15:954–960.Google Scholar
5. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95.Google Scholar
6. EUnetHTA 2013. Endpoints used for relative effectiveness assessment of pharmaceuticals. Clinical endpoints. http://www.eunethta.eu/outputs/methodological-guideline-rea-pharmaceuticals-clinical-endpoints (accessed February 11, 2015).Google Scholar
7. European Medicines Agency. Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products. London: EMA; January 2006. EMEA/CHMP/EWP/139391/2004. http://www.ispor.org/workpaper/emea-hrql-guidance.pdf (accessed February 11, 2015).Google Scholar
8. U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims. December 2009. http://www.fda.gov/downloads/Drugs/Guidances/UCM193282.pdf (accessed February 11, 2015).Google Scholar
9. EUnetHTA 2013. Endpoints used for relative effectiveness assessment of pharmaceuticals. Health related quality of life and utility measures. http://www.eunethta.eu/outputs/methodological-guideline-rea-pharmaceuticals-health-related-quality-life (accessed February 11, 2015).Google Scholar
10. Perspectives on biomarker and surrogate endpoint evaluation: Discussion forum summary. Institute of Medicine (US) Committee on Qualification of Biomarkers and Surrogate Endpoints in Chronic Disease. Washington, DC: National Academies Press (US); 2011. ISBN-13:978-0-309-16324-8ISBN-10:0-309-16324-2Google Scholar
11. Fleming, TR, De Mets, DL. Surrogate end points in clinical trials: Are we being misled? Ann Intern Med. 1996;125:605–613.Google Scholar
12. Taylor, RS, Elston, J. The use of surrogate outcomes in model-based cost effectiveness analyses: A survey of UK Health Technology Assessment reports. Health Technol Assess. 2009;13:iii, ix-xi.Google Scholar
13. EUnetHTA 2013. Endpoints used for relative effectiveness assessment of pharmaceuticals. Surrogate endpoints. http://www.eunethta.eu/outputs/methodological-guideline-rea-pharmaceuticals-surrogate-endpoints (accessed February 11, 2015).Google Scholar
14. Ciani, O, Buyse, M, Garside, R, et al. Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study. BMJ. 2013;346:f457.Google Scholar
15. EUnetHTA 2013. Endpoints used for relative effectiveness assessment of pharmaceuticals. Composite endpoints. http://www.eunethta.eu/outputs/methodological-guideline-rea-pharmaceuticals-composite-endpoints (accessed February 11, 2015).Google Scholar
16. Food and Drug Administration (FDA), Department of health and human services. Proposal to withdraw approval for the breast cancer indication for Avastin (Bevacizumab). November 18, 2011. FDA-2010-N-0621. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm193900.htm (accessed February 11, 2015).Google Scholar
17. Wieseler, B, McGauran, N, Kaiser, T. Drug studies: A tale of hide and seek. BMJ. 2010;341:c4942.Google Scholar
18. Health Information and Quality Authority. Guidelines for evaluating the clinical effectiveness of health technologies in Ireland. 23 November 2011. http://www.hiqa.ie/publications/guidelines-evaluating-clinical-effectiveness-health-technologies-ireland (accessed February 11, 2015).Google Scholar