Abstract
Biomarkers are defined as anatomic, physiologic, biochemical, molecular, or genetic parameters associated with the presence, absence, or severity of a disease process. As such, biomarkers may be useful as prognostic and diagnostic tests. Establishing the utility of a given biomarker as a prognostic or diagnostic test requires the conduct of carefully designed cohort studies in which the biomarker and the outcome of interest are measured independently. The design and analysis of such studies is discussed.
Surrogate outcomes in clinical trials consist of events or biomarkers intended to reflect important clinical outcomes. Surrogate outcomes may offer advantages in providing statistically robust estimates of treatment effects with smaller sample sizes. However, to be useful, surrogate outcomes have to be validated to ensure that the effect of therapy on them truly reflects the effect of therapy on the important clinical outcomes of interest.
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References
1. Wagener, G., Jan, M., Kim, M., Mori, K., Barasch, J. M., Sladen, R. N., Lee, H. T. (2006). Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 105, 485–491.
2. Biomarkers Definitions Working Group. (2001). Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Therap 69, 89–95.
3. Wang, T. J., Gona, P., Larson, M. G., Tofler, G. H., Levy, D., Newton-Cheh, C., Jacques, P. F., Rifai, N., Selhub, J., Robins, S. J., Benjamin, E. J., D'Agostino, R. B., Vasan, R. S. (2006). Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 355, 2631–2639.
4. Sackett, D., Haynes, R., Guyatt, G., Tugwell, P. (1991). The interpretation of diagnostic data, in Clinical Epidemiology: A Basic Science for Clinical Medicine, 2nd ed. Little, Brown and Company, Toronto.
5. Kleinbaum, D. G. (1996). Survival Analysis: A Self-Learning Text. Springer-Verlag, New York.
6. Cox, D. R., Oakes, D. (1984). Analysis of Survival Data. Chapman and Hall/CRC, Boca Raton, FL.
7. Pencina, M. J., D'Agostino, R. B. (2004). Overall C as a measure of discrimination in survival analysis: Model specific population value and confidence interval estimation. Stat Med 23, 2109–2123.
8. Peduzzi, P., Concato, J., Kemper, E.,. Holford, T. R., Feinstein, A. (1996). A simulation of the number of events per variable in logistic regression analysis. J Clin Epidemiol 99, 1373–1379.
9. Hanley, J., McNeil, B. (1982). The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143, 29–36.
10. Mulherin, S. A., Miller, W. C. (2002). Spectrum bias or spectrum effect? Subgroup variation in diagnostic test evaluation. Ann Intern Med 137, 598–602.
11. Nissen, S. E., Tardif, J. C., Nicholls, S. J., Revkin, J. H., Shear, C. L., Duggan, W. T., Ruzyllo, W., Bachinsky, W. B., Lasala, G. P., Tuzcu, E. M., ILLUSTRATE Investigators. (2007) Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 356, 1304–1316.
12. LaRosa, J. C., Grundy, S. M., Waters, D. D., Shear, C., Barter, P., Fruchart, J. C., Gotto, A. M., Greten, H., Kastelein, J. J., Shepherd, J., Wenger, N. K. (2005) Treating to new targets (TNT) investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 352, 1425–1435.
13. Baker A. G., Kramer B. S. (2003). A perfect correlate does not a surrogate make. BMC Med Res Methodol 3, 16–21.
14. Prentice R. L. (1989). Surrogate endpoints in clinical trials: Definitions and operational criteria. Stat Med 8, 431–430.
15. Gail, M. H., Pfeiffer, R., Houwelingen, H. C., Carroll, R. J. (2001). On meta-analytic assessment of surrogate outcomes. Biostatistics 3, 231–246.
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© 2008 Humana Press, a part of Springer Science+Business Media, LLC
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Rigatto, C., Barrett, B.J. (2008). Biomarkers and Surrogates in Clinical Studies. In: Barrett, B., Parfrey, P. (eds) Clinical Epidemiology. Methods in Molecular Biology™, vol 473. Humana Press. https://doi.org/10.1007/978-1-59745-385-1_8
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DOI: https://doi.org/10.1007/978-1-59745-385-1_8
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