Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.

Marissa N Lassere; Kent R Johnson; Maarten Boers; Peter Tugwell; Peter Brooks; Lee Simon; Vibeke Strand; Philip G Conaghan; Mikkel Ostergaard; Walter P Maksymowych; Robert Landewe; Barry Bresnihan; Paul-Peter Tak; Richard Wakefield; Philip Mease; Clifton O Bingham; Michael Hughes; Doug Altman; Marc Buyse; Sally Galbraith; George Wells

Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.

Marissa N Lassere, Kent R Johnson, Maarten Boers, Peter Tugwell, Peter Brooks, Lee Simon, Vibeke Strand, Philip G Conaghan, Mikkel Ostergaard, Walter P Maksymowych, Robert Landewe, Barry Bresnihan, Paul-Peter Tak, Richard Wakefield, Philip Mease, Clifton O Bingham, Michael Hughes, Doug Altman, Marc Buyse, Sally GalbraithGeorge Wells

100 Citations (Scopus)

Abstract

OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. METHODS: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

Original language	English
Journal	Journal of Rheumatology
Volume	34
Issue number	3
Pages (from-to)	607-15
Number of pages	8
ISSN	0315-162X
Publication status	Published - 2007

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Lassere, M. N., Johnson, K. R., Boers, M., Tugwell, P., Brooks, P., Simon, L., Strand, V., Conaghan, P. G., Ostergaard, M., Maksymowych, W. P., Landewe, R., Bresnihan, B., Tak, P-P., Wakefield, R., Mease, P., Bingham, C. O., Hughes, M., Altman, D., Buyse, M., ... Wells, G. (2007). Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema. Journal of Rheumatology, 34(3), 607-15. http://www.jrheum.com/subscribers/07/03/607.html

Lassere, MN, Johnson, KR, Boers, M, Tugwell, P, Brooks, P, Simon, L, Strand, V, Conaghan, PG, Ostergaard, M, Maksymowych, WP, Landewe, R, Bresnihan, B, Tak, P-P, Wakefield, R, Mease, P, Bingham, CO, Hughes, M, Altman, D, Buyse, M, Galbraith, S & Wells, G 2007, 'Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.', Journal of Rheumatology, vol. 34, no. 3, pp. 607-15. <http://www.jrheum.com/subscribers/07/03/607.html>

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abstract = "OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. METHODS: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term {"}surrogate{"} be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.",

author = "Lassere, {Marissa N} and Johnson, {Kent R} and Maarten Boers and Peter Tugwell and Peter Brooks and Lee Simon and Vibeke Strand and Conaghan, {Philip G} and Mikkel Ostergaard and Maksymowych, {Walter P} and Robert Landewe and Barry Bresnihan and Paul-Peter Tak and Richard Wakefield and Philip Mease and Bingham, {Clifton O} and Michael Hughes and Doug Altman and Marc Buyse and Sally Galbraith and George Wells",

year = "2007",

language = "English",

volume = "34",

pages = "607--15",

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T1 - Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.

AU - Lassere, Marissa N

AU - Johnson, Kent R

AU - Boers, Maarten

AU - Tugwell, Peter

AU - Brooks, Peter

AU - Simon, Lee

AU - Strand, Vibeke

AU - Conaghan, Philip G

AU - Ostergaard, Mikkel

AU - Maksymowych, Walter P

AU - Landewe, Robert

AU - Bresnihan, Barry

AU - Tak, Paul-Peter

AU - Wakefield, Richard

AU - Mease, Philip

AU - Bingham, Clifton O

AU - Hughes, Michael

AU - Altman, Doug

AU - Buyse, Marc

AU - Galbraith, Sally

AU - Wells, George

PY - 2007

Y1 - 2007

N2 - OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. METHODS: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

AB - OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. METHODS: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

M3 - Journal article

SN - 0315-162X

VL - 34

SP - 607

EP - 615

JO - Journal of Rheumatology

JF - Journal of Rheumatology

IS - 3

ER -

Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.

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