Hepatology may have problems with putative surrogate outcome measures Christian Gluud, Jesper Brok, Yan Gong, Ronald L. Koretz  Journal of Hepatology  Volume 46, Issue 4, Pages 734-742 (April 2007) DOI: 10.1016/j.jhep.2007.01.003 Copyright © 2007 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Basics of validation of a potential surrogate outcome measure (I). In order to function as a potential surrogate, the treatment (TR) must be instituted before the surrogate outcome measure (SO) is evaluated. Further, the evaluation of the surrogate outcome measure must occur before measuring the clinical outcome (CO). Based on Buyse et al. [2]. [This figure appears in colour on the web.] Journal of Hepatology 2007 46, 734-742DOI: (10.1016/j.jhep.2007.01.003) Copyright © 2007 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Basics of validation of a potential surrogate outcome measure (II). In order to function as a potential surrogate, the surrogate outcome measure (SO) must be correlated to the clinical outcome measure (CO). This can be shown in an observational study or in a randomised trial. When the correlation is established it is time to go to the next step in the validation of the potential surrogate for the offered treatment (TR): please see Fig. 3. Based on Buyse et al. [2]. [This figure appears in colour on the web.] Journal of Hepatology 2007 46, 734-742DOI: (10.1016/j.jhep.2007.01.003) Copyright © 2007 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Basics of validation of a potential surrogate outcome measure (III). In order to become a validated surrogate outcome measure for the offered treatment (TR) randomised trials ought to establish that the treatment has significant beneficial effects on the potential surrogate outcome measure (SO) and the clinical outcome measure (CO). The evaluation of the surrogate outcome and the clinical outcome measure is best performed based on data from meta-analyses of several randomised trials on the topic. Based on Buyse et al. [2]. [This figure appears in colour on the web.] Journal of Hepatology 2007 46, 734-742DOI: (10.1016/j.jhep.2007.01.003) Copyright © 2007 European Association for the Study of the Liver Terms and Conditions